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Sample records for antidepressant nonresponders studied

  1. Antidepressants

    MedlinePlus

    Antidepressants are medicines that treat depression. Your doctor can prescribe them for you. They work to balance ... them to help. There are several types of antidepressants. You and your doctor may have to try ...

  2. What is wrong with non-respondents? Alcohol-, drug- and smoking related mortality and morbidity in a 12-year follow up study of respondents and non-respondents in the Danish Health and Morbidity Survey

    PubMed Central

    Christensen, Anne Illemann; Ekholm, Ola; Gray, Linsay; Glümer, Charlotte; Juel, Knud

    2015-01-01

    Background and aim Response rates in health surveys have diminished over the last two decades, making it difficult to obtain reliable information on health and health-related risk factors in different population groups. This study compared cause-specific mortality and morbidity among survey respondents and different types of non-respondents to estimate alcohol-, drug- and smoking related mortality and morbidity among non-respondents. Design Prospective follow-up study of respondents and non-respondents in two cross-sectional health surveys. Setting Denmark. Participants A total sample of 39,540 Danish citizens aged 16 or older. Measurements Register-based information on cause-specific mortality and morbidity at the individual level was obtained for respondents (n=28,072) and different types of non-respondents (refusals n=8,954; illness/disabled n=731, uncontactable n=1,593). Cox proportional hazards models were used to examine differences in alcohol-, drug- and smoking-related mortality and morbidity, respectively, in a 12 year follow-up period. Findings Overall, non-response was associated with a significantly increased hazard ratio of 1.56 (95% CI: 1.36–1.78) for alcohol-related morbidity, 1.88 (95% CI: 1.38–2.57) for alcohol-related mortality, 1.55 (95% CI: 1.27–1.88) for drug-related morbidity, 3.04 (95% CI: 1.57–5.89) for drug-related mortality and 1.15 (95% CI: 1.03–1.29) for smoking-related morbidity. The hazard ratio for smoking-related mortality also tended to be higher among non-respondents compared with respondents although no significant association was evident (HR: 1.14; 95% CI: 0.95-1.36). Uncontactable and ill/disabled non-respondents generally had a higher hazard ratio of alcohol-, drug- and smoking related mortality and morbidity compared with refusal non-respondents. Conclusion Health survey non-respondents in Denmark have an increased hazard ratio of alcohol-, drug-, and smoking-related mortality and morbidity compared with respondents

  3. Study Questions Use of Antidepressants for Children, Teens

    MedlinePlus

    ... html Study Questions Use of Antidepressants for Children, Teens They were seen as mostly ineffective and sometimes ... June 8, 2016 (HealthDay News) -- Treating children and teens suffering from depression with antidepressants may be both ...

  4. Study Finds No Heart Risk from SSRI Antidepressants

    MedlinePlus

    ... html Study Finds No Heart Risk From SSRI Antidepressants Prozac actually appeared to protect against heart attack, ... WEDNESDAY, March 23, 2016 (HealthDay News) -- Widely used antidepressants known as selective serotonin reuptake inhibitors (SSRIs) don' ...

  5. Endometrial cancer and antidepressants: A nationwide population-based study.

    PubMed

    Lin, Chiao-Fan; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Liang, Hsin-Yi; Chiu, Wei-Che; Huang, Kuo-You; Lee, Yena; McIntyre, Roger S; Chen, Vincent Chin-Hung

    2016-07-01

    To our knowledge, the association between antidepressant exposure and endometrial cancer has not been previously explored. Herein, we aim to investigate the association between antidepressant prescription, including novel antidepressants, and the risk for endometrial cancer in a population-based study.Data for the analysis were derived from National Health Insurance Research Database. We identified 8392 cases with a diagnosis of endometrial cancer and 82,432 matched controls. A conditional logistic regression model was used, with adjusting for potentially confounding variables (e.g., comorbid psychiatric diseases, comorbid physical diseases, and other medications). Risk for endometrial cancer in the population-based study sample was categorized by, and assessed as a function of, antidepressant prescription and cumulative dosage.We report no association between endometrial cancer incidence and antidepressant prescription, including those prescribed either selective serotonin reuptake inhibitors (adjusted odds ratio [OR] = 0.98; 95% confidence interval [CI], 0.84-1.15) or serotonin norepinephrine reuptake inhibitors (adjusted OR = 1.14; 95% CI, 0.76-1.71). We also did not identify an association between higher cumulative doses of antidepressant prescription and endometrial cancer.There was no association between antidepressant prescription and endometrial cancer. PMID:27442640

  6. Antigen binding and capping by lymphocytes of genetic nonresponder mice.

    PubMed

    Dunham, E K; Unanue, E R; Benacerraf, B

    1972-08-01

    Radioautographic study of the binding of GAT-(125)I to spleen cells of genetic responder and nonresponder mice demonstrates that among mice not injected with antigen all strains have approximately the same number of antigen-binding cells; after injection with antigen the number of antigen-binding cells increases in responders but not in nonresponders. Nonresponders are shown to make antibody after injection with GAT complexed with an immunogenic carrier, demonstrating the presence of potentially functional B cells in responders and nonresponders alike. When incubated in the warm, antigen-binding cells of both responders and nonresponders concentrate antigen at one pole of the cell, forming caps. PMID:5043419

  7. Do antidepressants cause folic acid depletion? A pilot study

    PubMed Central

    Farrell, K.A.; Jamjoom, S.; Donaldson, D.; Dickerson, J.W.T.

    1988-01-01

    Chronic administration of tricyclic antidepressants is common; folic acid depletion is a potential consequence adversely affecting the mental state. In a pilot study prior to research in the community, serum and red cell folate and serum vitamin B 12 levels were measured in the following elderly psychiatric inpatients: 14 controls (patients not receiving any drugs with known antifolate activity), 11 receiving tricyclic antidepressants, 13 receiving antipsychotics (phenothiazines) and four receiving an anticonvulsant (carbamazepine). Patients on prolonged treatment with carbamazepine or phenothiazine drugs had lower concentrations of folate in serum and erythrocytes compared with controls; the decrease was statistically significant for the effect of phenothiazines on serum folate levels. Tricyclic antidepressants, which are in widespread use in the community, did not cause folate depletion during the first two years of treatment. PMID:3204543

  8. Cost-benefit analysis of newer versus older antidepressants--pharmacoeconomic studies comparing SSRIs/SNRIs with tricyclic antidepressants.

    PubMed

    Laux, G

    2001-01-01

    Changes in the social and health services over the last years have forced doctors to concern themselves with cost benefit calculations and budget forecasting. Cost considerations are a (co-) determinant in the choice of antidepressants as well as neuroleptics and/or antipsychotics. In recent years, pharmacoeconomic studies have been performed to answer the question as to what extent treatment with new antidepressants, in particular SSRIs, is actually less expensive than treatment with (generic) tricyclic antidepressants due to better safety profiles and higher compliance in spite of the considerably higher retail price. Following descriptions of the methodological principles, the currently available studies are presented and discussed critically in this report. It can be stated that the economic value of different antidepressants can not be decided definitively at the present time. The available data do not allow the conclusion that SSRIs should be preferred over tricyclic antidepressants with the argument that the treatment as a whole is more cost effective in spite of the higher costs. PMID:11229615

  9. Contactable Non-responders Show Different Characteristics Compared to Lost to Follow-Up Participants: Insights from an Australian Longitudinal Birth Cohort Study.

    PubMed

    Ng, Shu-Kay; Scott, Rani; Scuffham, Paul A

    2016-07-01

    Objective This research aims to identify predictors of attrition in a longitudinal birth cohort study in Australia and assess differences in baseline characteristics and responses in subsequent follow-up phases between contactable non-responders and uncontactable non-responders deemed "lost to follow-up (LTF)". Methods 3368 women recruited from three public hospitals in Southeast Queensland and Northern New South Wales during antenatal visits in 2006-2011 completed a baseline questionnaire to elicit information on multiple domains of exposures. A follow-up questionnaire was posted to each participant at 1 year after birth to obtain mother's and child's health and development information. Multivariate logistic regression was used to model the association between exposures and respondents' status at 1 year. The effect of an inverse-probability-weighting method to adjust for non-response was studied. Results Overall attrition at 1-year was 35.4 %; major types of attrition were "contactable non-response" (27.6 %) and "LTF" (6.7 %). These two attrition types showed different responses at the 3-year follow-up and involved different predictors. Besides shared predictors (first language not English, higher risk of psychological distress, had smoked during pregnancy, higher levels of family conflict), distinguishable predictors of contactable non-responders were younger age, having moved home in the past year and having children under 16 in the household. Attrition rates increased substantially from 20 % in 2006 to 54 % in 2011. Conclusions This observed trend of increased attrition rates raises concern about the use of traditional techniques, such as "paper-based" questionnaires, in longitudinal cohort studies. The supplementary use of electronic communications, such as online survey tools and smart-device applications, could provide a better alternative. PMID:26976281

  10. Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study.

    PubMed

    Baldomero, E Baca; Ubago, J Giner; Cercós, C Leal; Ruiloba, J Vallejo; Calvo, C García; López, R Prieto

    2005-01-01

    Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used as an alternative treatment for depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant. This randomized, open-label, multicenter study compared the effectiveness of the SNRI venlafaxine extended release (VXR) with that of conventional antidepressants (CA) in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a CA in a primary care setting. Patients with a Hamilton Depression Rating Scale (HAM-D17) score > or =17 were randomly assigned to treatment with an alternative CA or VXR. Remission was defined as a score < or =7 on the HAM-D17. Efficacy analyses were carried out on 3,097 patients from the intent-to-treat (ITT) population (1,632 VXR; 1,465 CA). The antidepressants prescribed most frequently in the CA group were paroxetine (21.3%), citalopram (20.1%), sertraline (19.1%), fluoxetine (17.0%), and mirtazapine (7.9%). After 24 weeks of treatment, the VXR group demonstrated a significantly higher remission rate than did the CA group (59.3% VXR; 51.5% CA; P<.0001; odds ratio: 1.37; 95% CI: 1.19-1.58; P<.01). Despite the limitations of the open design, the results of this study suggest that venlafaxine extended release may be more effective than the conventional antidepressants used in this study when treating depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant. PMID:16094658

  11. [Comparative study of discriminative stimulus properties of antidepressants].

    PubMed

    Korolev, A O; Kalinina, T S; Volkova, A V; Mokrov, G V; Kudriashov, N V; Voronina, T A

    2014-01-01

    Interoceptive stimulus properties of amitriptyline (54 mg/kg body weight), fluoxetine (10 mg/kg), and pyrrolo[1,2-a][1,4]diazepine derivative GMAL-24 (10 mg/kg) were studied in a standard operant model with liquid reinforcement of drug discrimination (DD) in male Wistar rats. A new experimental schedule that includes subchronic (7-day) administration of a training drug was used to perform DD learning. For the first time, it was found that amitriptyline has a discriminative interoceptive stimulus properties. Neither fluoxetine nor GMAL-24 did exhibit interoceptive properties. Imipramine (15 mg/kg, i.p.) fully substitutes for amitriptyline stimulus in substitution test. Fluoxetine (5 - 20 mg/kg, i.p.) failed to substitute with amitriptyline. Thus, amitriptyline/saline drug discrimination should be used for a comparative analysis of the central mechanisms of action of psychotropic substances, rather than for screening specific antidepressant activity. PMID:25322645

  12. No change in N-acetyl aspartate in first episode of moderate depression after antidepressant treatment: 1H magnetic spectroscopy study of left amygdala and left dorsolateral prefrontal cortex

    PubMed Central

    Bajs Janović, Maja; Kalember, Petra; Janović, Špiro; Hrabač, Pero; Folnegović Grošić, Petra; Grošić, Vladimir; Radoš, Marko; Henigsberg, Neven

    2014-01-01

    Background The role of brain metabolites as biological correlates of the intensity, symptoms, and course of major depression has not been determined. It has also been inconclusive whether the change in brain metabolites, measured with proton magnetic spectroscopy, could be correlated with the treatment outcome. Methods Proton magnetic spectroscopy was performed in 29 participants with a first episode of moderate depression occurring in the left dorsolateral prefrontal cortex and left amygdala at baseline and after 8 weeks of antidepressant treatment with escitalopram. The Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory were used to assess the intensity of depression at baseline and at the endpoint of the study. At endpoint, the participants were identified as responders (n=17) or nonresponders (n=12) to the antidepressant therapy. Results There was no significant change in the N-acetyl aspartate/creatine ratio (NAA/Cr) after treatment with antidepressant medication. The baseline and endpoint NAA/Cr ratios were not significantly different between the responder and nonresponder groups. The correlation between NAA/Cr and changes in the scores of clinical scales were not significant in either group. Conclusion This study could not confirm any significant changes in NAA after antidepressant treatment in the first episode of moderate depression, or in regard to therapy response in the left dorsolateral prefrontal cortex or left amygdala. Further research is necessary to conclude whether NAA alterations in the first episode of depression could possibly be different from chronic or late-onset depression, and whether NAA alterations in stress-induced (reactive) depression are different from endogenous depression. The potential role of NAA as a biomarker of a treatment effect has yet to be established. PMID:25278754

  13. Study Questions Use of Antidepressants for Children, Teens

    MedlinePlus

    ... than they do in adults," said Dr. Peter Kramer. He is a clinical professor emeritus of psychiatry ... has always stood out as relatively more effective," Kramer said. But it isn't clear how antidepressants ...

  14. Long-term prescribing of antidepressants in the older population: a qualitative study

    PubMed Central

    Dickinson, Rebecca; Knapp, Peter; House, Allan O; Dimri, Vandana; Zermansky, Arnold; Petty, Duncan; Holmes, John; Raynor, David K

    2010-01-01

    Background High rates of long-term antidepressant prescribing have been identified in the older population. Aims To explore the attitudes of older patients and their GPs to taking long-term antidepressant therapy, and their accounts of the influences on long-term antidepressant use. Design of study Qualitative study using in-depth semi-structured interviews. Setting One primary care trust in North Bradford. Method Thirty-six patients aged ≥75 years and 10 GPs were interviewed. Patients were sampled to ensure diversity in age, sex, antidepressant type, and home circumstances. Results Participants perceived significant benefits and expressed little apprehension about taking long-term antidepressants, despite being aware of the psychological and social factors involved in onset and persistence of depression. Barriers to discontinuation were identified following four themes: pessimism about the course and curability of depression; negative expectations and experiences of ageing; medicine discontinuation perceived by patients as a threat to stability; and passive (therapeutic momentum) and active (therapeutic maintenance) decisions to accept the continuing need for medication. Conclusion There is concern at a public health level about high rates of long-term antidepressant prescribing, but no evidence was found of a drive for change either from the patients or the doctors interviewed. Any apprehension was more than balanced by attitudes and behaviours supporting continuation. These findings will need to be incorporated into the planning of interventions aimed at reducing long-term antidepressant prescribing in older people. PMID:20353660

  15. Effectiveness of antidepressant treatments in pre-menopausal versus post-menopausal women: a pilot study on differential effects of sex hormones on antidepressant effects.

    PubMed

    Pae, Chi-Un; Mandelli, Laura; Kim, Tae-Suk; Han, Changsu; Masand, Prakash S; Marks, David M; Patkar, Ashwin A; Steffens, David C; De Ronchi, Diana; Serretti, Alessandro

    2009-03-01

    The incidence or recurrence of major depression is greatly increased in women during the transition to and after menopause and hormonal changes occurring during these periods are thought to play an important role in depressive recurrence. It has been also suggested that a chronic hypoestrogenic state may reduce the response to antidepressant drugs, but whether or not, and the extent to which hormonal changes related to menopause influence the response to antidepressant drugs, is yet to be determined. Thirty-nine female patients (n=17 in pre-menopause; n=22 in post-menopause) with major depressive disorder (MDD) based on DSM-IV criteria, who were not on hormonal replacement therapy, participated in the study in order to prospectively evaluate the effect of menopausal status and its hormonal correlates on the effectiveness of antidepressant treatment for 6weeks. The Hamilton Depression Rating Scale-17 item (HAMD), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Severity scale (CGI-S) were administered at baseline, week 1, week 3, and week 6. The CGI-I scale was also assessed at weeks 1, 3, and 6. After controlling for age, age at onset, baseline symptom severity, antidepressant dosage and hormonal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), post-menopausal women showed a poor response to antidepressants over 6weeks of treatment, compared to the response of pre-menopausal women. Old age and high levels of FSH were also associated with the efficacy of antidepressants in post-menopausal women. In conclusion, sex hormones are known to interact with serotonergic, noradrenergic and dopaminergic systems. Despite methodological limitations, our study suggests that menopausal status and old age are predictors of a poor response to antidepressant treatment. Furthermore, the FSH may interfere with the mechanism of action of the antidepressant agents. Hence, larger, randomized and controlled

  16. Study of antidepressant drugs in GPR39 (zinc receptor⁻/⁻) knockout mice, showing no effect of conventional antidepressants, but effectiveness of NMDA antagonists.

    PubMed

    Młyniec, Katarzyna; Gaweł, Magdalena; Nowak, Gabriel

    2015-01-01

    The monoamine-based antidepressants that are currently used generate many side effects, and more than 30% of depressed patients do not respond to this therapy. Glutamate-based antidepressants seem to play an important role in therapy for depression, but there is still an extensive search for safe drugs. An antagonist of the glutamatergic NMDA receptor - namely, zinc - plays a part in maintaining homeostasis between glutamate and GABA via the GPR39 receptor, which has been found to be involved in the pathophysiology of depression. In this study we investigated the behavioral response resulting from chronic or acute treatment with monoamine-based antidepressants, such as imipramine, escitalopram or reboxetine, and from glutamate-based MK-801 or ketamine, as measured by the forced swim test (FST) in GPR39 knockout (GPR39 KO, -/-) mice versus wild-type (WT, +/+) controls. All the tested agents reduced the immobility time in the FST in the wild-type animals. However, only chronic or acute administration of MK-801 and ketamine (but not monoamine-based antidepressants) were active in the FST in GPR39 KO mice. Our results show for the first time that GPR39 is required for the antidepressant effect of monoamine-based antidepressants. PMID:25827929

  17. Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

    PubMed Central

    Yeh, Yi-Wei; Ho, Pei-Shen; Kuo, Shin-Chang; Chen, Chun-Yen; Liang, Chih-Sung; Yen, Che-Hung; Huang, Chang-Chih; Ma, Kuo-Hsing; Shiue, Chyng-Yann; Huang, Wen-Sheng; Shyu, Jia-Fwu; Wan, Fang-Jung; Lu, Ru-Band

    2015-01-01

    Background: Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants. Methods: We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more. Results: Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders. Conclusions: The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD. PMID:25568284

  18. Antidepressants and risks of suicide and suicide attempts: a 27-year observational study

    PubMed Central

    Leon, AC; Solomon, DA; Li, C; Fiedorowicz, JG; Coryell, WH; Endicott, J; Keller, MB

    2013-01-01

    OBJECTIVE The 2007 revision of the black box warning for suicidality with antidepressants states that patients of all ages who initiate antidepressants should be monitored for clinical worsening or suicidality. The objective of this study was to examine the association of antidepressants with suicide attempts and with suicide deaths. METHOD A longitudinal, observational study of mood disorders with prospective assessments for up to 27 years was conducted at 5 US academic medical centers. The study sample included 757 participants who enrolled from 1979 to 1981 during an episode of mania, depression, or schizoaffective disorder, each based on Research Diagnostic Criteria. Unlike randomized controlled clinical trials of antidepressants, the analyses included participants with psychiatric and other medical comorbidity and those receiving acute or maintenance therapy, polypharmacy, or no psychopharmacologic treatment at all. Over follow-up, these participants had 6,716 time periods that were classified as either exposed to an antidepressant or not exposed. Propensity score-adjusted mixed-effects survival analyses were used to examine risk of suicide attempt or suicide, the primary outcome. RESULTS The propensity model showed that antidepressant therapy was significantly more likely when participants' symptom severity was greater (odds ratio [OR] = 1.16; 95% CI, 1.12–1.21; z = 8.22; P < .001) or when it was worsening (OR = 1.69; 95% CI, 1.50–1.89; z = 9.02; P < .001). Quintile-stratified, propensity-adjusted safety analyses using mixed-effects grouped-time survival models indicate that the risk of suicide attempts or suicides was reduced by 20% among participants taking antidepressants (hazard ratio, 0.80; 95% CI, 0.68–0.95; z = −2.54; P = .011). CONCLUSIONS This longitudinal study of a broadly generalizable cohort found that, although those with more severe affective syndromes were more likely to initiate treatment, antidepressants were associated with a

  19. Antidepressant Use and Lifetime History of Mental Disorders in a Community Sample: Results from the Baltimore Epidemiologic Catchment Area Study

    PubMed Central

    Takayanagi, Yoichiro; Spira, Adam P.; Bienvenu, O. Joseph; Hock, Rebecca S.; Carras, Michelle C.; Eaton, William W.; Mojtabai, Ramin

    2015-01-01

    Objectives Past studies have shown that many individuals who use antidepressants do not have a current or lifetime history of mental disorders. However, recent studies suggest that the one-time retrospective evaluation of mental disorders commonly used in such studies may substantially underestimate the true lifetime prevalence of mental disorders. We examined the prevalence of mental disorders, assessed prospectively over multiple interviews, among individuals currently using antidepressants in a community sample. Methods Using data from the Baltimore Epidemiologic Catchment Area (ECA) Survey Wave 1 (1981) through Wave 4 (2004) (N = 1071), we assessed lifetime prevalence of common mood and anxiety disorders according to the DSM-III and DSM-III-R criteria, based on 4 interviews, among participants who reported current antidepressant use. Furthermore, we examined factors associated with current antidepressant use. Results Thirteen percent of participants at Wave 4 reported currently using antidepressant medications. Among antidepressant users, 69% never met criteria for major depressive disorder (MDD), and 38% never met criteria for MDD, obsessive-compulsive disorder, panic disorder, social phobia, or generalized anxiety disorder in their lifetime. Female gender, Caucasian ethnicity, recent or current physical problems (e.g., loss of bladder control, hypertension and back pain) and recent mental health facility visits were associated with antidepressant use in addition to mental disorders. Conclusions Many individuals who are prescribed and use antidepressant medications may not have met criteria for mental disorders. Our data indicate that antidepressants are commonly used in the absence of clear evidence-based indications. PMID:25188822

  20. Cancer Mortality in People Treated with Antidepressants before Cancer Diagnosis: A Population Based Cohort Study

    PubMed Central

    Sun, Yuelian; Vedsted, Peter; Fenger-Grøn, Morten; Wu, Chun Sen; Bech, Bodil Hammer; Olsen, Jørn; Benros, Michael Eriksen; Vestergaard, Mogens

    2015-01-01

    Background Depression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis. Methods and Findings We conducted a population based cohort study of all adults diagnosed with cancer between January 2003 and December 2010 in Denmark (N = 201,662). We obtained information on cancer from the Danish Cancer Registry, on the day of death from the Danish Civil Registry, and on redeemed antidepressants from the Danish National Prescription Registry. Current users of antidepressants were defined as those who redeemed the latest prescription of antidepressant 0–4 months before cancer diagnosis (irrespective of earlier prescriptions), and former users as those who redeemed the latest prescription five or more months before cancer diagnosis. We estimated an all-cause one-year mortality rate ratio (MRR) and a conditional five-year MRR for patients who survived the first year after cancer diagnosis and confidence interval (CI) using a Cox proportional hazards regression model. Overall, 33,111 (16.4%) patients redeemed at least one antidepressant prescription in the three years before cancer diagnosis of whom 21,851 (10.8%) were current users at the time of cancer diagnosis. Current antidepressant users had a 32% higher one-year mortality (MRR = 1.32, 95% CI: 1.29–1.35) and a 22% higher conditional five-year mortality (MRR = 1.22, 95% CI: 1.17–1.26) if patients survived the first year after the cancer diagnosis than patients not redeeming antidepressants. The one-year mortality was particularly high for patients who initiated antidepressant treatment within four months before cancer diagnosis (MRR = 1.54, 95% CI: 1.47–1.61). Former users had no increased cancer mortality. Conclusions Initiation of antidepressive treatment prior to cancer diagnosis is

  1. Antidepressants and the risk of hyponatremia: a Danish register-based population study

    PubMed Central

    Leth-Møller, Katja Biering; Hansen, Annette Højmann; Torstensson, Maia; Andersen, Stig Ejdrup; Ødum, Lars; Gislasson, Gunnar; Torp-Pedersen, Christian; Holm, Ellen Astrid

    2016-01-01

    Objective To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia. Design Retrospective register-based cohort study using nationwide registers from 1998 to 2012. Setting The North Denmark Region. Participants In total, 638 352 individuals were included. Primary and secondary outcome measures Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models. Results An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14). Conclusions All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine. PMID:27194321

  2. Antidepressants and Gastric Cancer: A Nationwide Population-Based Nested Case-Control Study

    PubMed Central

    Lin, Chiao-Fan; Chan, Hsiang-Lin; Liang, Hsin-Yi; Lee, Yena; McIntyre, Roger S.; Chen, Vincent Chin-Hung

    2015-01-01

    Background To our knowledge, no epidemiological study has reported on whether an association between antidepressant exposure and gastric cancer exists. Herein, we aim to investigate the possible association between antidepressant exposure and gastric cancer incidence. Methods Using a nested case-control design, we identified 26289 cases with gastric cancer and 127984 controls from Taiwan’s National Health Insurance Research Database (NHIRD). The data were analyzed using a conditional logistic regression model adjusting for possible confounding variables. Results We found antidepressant use did not increase the risk of gastric cancer. The lack of an association between antidepressant prescription and elevated gastric cancer incidence was apparent for across selective serotonin-reuptake inhibitors (SSRIs), tricyclic agents (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), reversible inhibitors of monoamine oxidase A (RIMA), trazodone, mirtazapine and bupropion. There were slightly decreased gastric cancer risks of SSRIs use (≧28 DDD group, adjusted OR = 0.87; 95% CI = 0.78–0.96). Sensitive analysis showed SSRIs, TCAs, and SNRIs did not increase gastric cancer risks significantly even in the group with peptic ulcer history. Conclusions An association between antidepressant exposure and gastric cancer was not apparent in this analysis. PMID:26606417

  3. Antidepressant Use and Body Mass Index Change in Overweight Adolescents: A Historical Cohort Study

    PubMed Central

    Biggs, Bridget K.; Oesterle, Tyler S.; Croarkin, Paul E.

    2014-01-01

    Objective: Given the limited empirical data on antidepressant use and weight change in children, we performed a historical cohort study to assess change in age- and sex-standardized body mass index associated with antidepressant use among overweight adolescents diagnosed with a depressive disorder. Methods: We systematically reviewed electronic medical records from a tertiary academic medical center and identified adolescents (age 13–18 years) who were overweight (body mass index >85th percentile) and had a depression diagnosis. Patients were seen from January 1, 2000, through January 1, 2010. Age- and sex-standardized body mass index scores were calculated at initiation of antidepressant medication and at the end of treatment. Unmedicated patients had baseline and final age- and sex-standardized body mass index calculated using the first and last recorded measurements in the study period (maximum time between measures was 5 years). Results: In total, 435 patients (301 female) met our inclusion criteria; of these, 255 were prescribed an antidepressant (selective serotonin reuptake inhibitor, serotonin norepinephrine reuptake inhibitor, tricyclic antidepressant, or dopamine-norepinephrine reuptake inhibitor). Age- and sex-standardized body mass index significantly increased (F1,193=14.34; P<0.001) only for adolescents treated with selective serotonin reuptake inhibitors. For patients receiving other medications or no medication, age- and sex-standardized body mass index did not change significantly. Conclusion: This study provides initial empiric evidence for a link between selective serotonin reuptake inhibitor use and weight gain in already overweight adolescents. Further study of antidepressant use and weight gain in other pediatric populations and in prospective studies is warranted. PMID:25621183

  4. A genome-wide association study points to multiple loci predicting antidepressant treatment outcome in depression

    PubMed Central

    Binder, Elisabeth B.; Bettecken, Thomas; Uhr, Manfred; Ripke, Stephan; Kohli, Martin A.; Hennings, Johannes M.; Horstmann, Sonja; Kloiber, Stefan; Menke, Andreas; Bondy, Brigitta; Rupprecht, Rainer; Domschke, Katharina; Baune, Bernhard T.; Arolt, Volker; Rush, A. John; Holsboer, Florian; Müller-Myhsok, Bertram

    2015-01-01

    Context Efficacy of antidepressant treatment in depression is unsatisfactory as one in three patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome. Objective To identify genetic and clinical determinants of antidepressant treatment outcome in depression. Design Genome-wide pharmacogenetic association study with two independent replication samples. Setting We performed a genome-wide association (GWA) study in patients from the Munich-Antidepressant-Response-Signature (MARS) project and in pooled DNA from an independent German replication sample. A set of 328 single nucleotide polymorphisms (SNPs) highly related to outcome in both GWA studies was genotyped in a sample of the Sequenced-Treatment-Alternatives-to-Relieve-Depression (STAR*D) study. Participants 339 inpatients suffering from a depressive episode (MARS sample), further 361 depressed inpatients (German replication sample), and 832 outpatients with major depression (STAR*D sample). Main Outcome Measures We generated a multi-locus genetic variable describing the individual number of alleles of the selected SNPs associated with beneficial treatment outcome in the MARS sample (“response” alleles) to evaluate additive genetic effects on antidepressant treatment outcome. Results Multi-locus analysis revealed a significant contribution of a binary variable categorizing patients as carriers of a high vs. low number of response alleles in predicting antidepressant treatment outcome in both samples, MARS and STAR*D. In addition, we observed that patients with a comorbid anxiety disorder in combination with a low number of response alleles showed the least favorable outcome. Conclusion Our results demonstrate the importance of multiple genetic factors in combination with clinical features to predict antidepressant treatment outcome underscoring the multifactorial nature of this trait. PMID

  5. Metabonomic Study on the Antidepressant-Like Effects of Banxia Houpu Decoction and Its Action Mechanism

    PubMed Central

    Ji, Weiwei; Qu, Rong; Wang, Mingyan; Yang, Wen; Zhan, Zhen; Ma, Shiping

    2013-01-01

    The aim of this study was to establish an experimental model for metabonomic profiles of the rat's brain and then to investigate the antidepressant effect of Banxia Houpu decoction (BHD) and its possible mechanisms. Behavioral research and metabonomics method based on UPLC-MS were used to assess the efficacy of different fractions of BHD on chronic unpredictable mild stress (CUMS) model of depression. There was a significant difference between the BHD group and the model group. Eight endogenous metabolites, which are contributing to the separation of the model group and control group, were detected, while BHD group regulated the perturbed metabolites showing that there is a tendency of recovery compared to control group. Therefore, we think that those potential metabolite biomarkers have some relationship with BHD's antidepression effect. This work appraised the antidepressant effect of Banxia Houpu decoction as well as revealing a metabonomics method, a valuable parameter in the TCM research. PMID:24250712

  6. Mouse Models for Studying Depression-Like States and Antidepressant Drugs.

    PubMed

    Bergner, Carisa L; Smolinsky, Amanda N; Hart, Peter C; Dufour, Brett D; Egan, Rupert J; LaPorte, Justin L; Kalueff, Allan V

    2016-01-01

    Depression is a common psychiatric disorder, with diverse symptoms and high comorbidity with other brain dysfunctions. Due to this complexity, little is known about the neural and genetic mechanisms involved in depression pathogenesis. In a large proportion of patients, current antidepressant treatments are often ineffective and/or have undesirable side effects, fueling the search for more effective drugs. Animal models mimicking various symptoms of depression are indispensable in studying the biological mechanisms of this disease. Here, we summarize several popular methods for assessing depression-like symptoms in mice, and their utility in screening antidepressant drugs. PMID:27150095

  7. Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression--The EMC trial.

    PubMed

    Tadić, André; Wachtlin, Daniel; Berger, Mathias; Braus, Dieter F; van Calker, Dietrich; Dahmen, Norbert; Dreimüller, Nadine; Engel, Alice; Gorbulev, Stanislav; Helmreich, Isabella; Kaiser, Anne-Katrin; Kronfeld, Kai; Schlicht, Konrad F; Tüscher, Oliver; Wagner, Stefanie; Hiemke, Christoph; Lieb, Klaus

    2016-04-01

    Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of < 20% on the Hamilton Depression Rating Scale (HAMD-17) after 14 days of treatment, and were randomly assigned to open treatment with the EMC strategy (n = 97; venlafaxine XR for study days 15-56; in case of sustained non-improvement on day 28, lithium augmentation for days 29-56) or TAU (n = 95; escitalopram continuation; non-responders on day 28 were switched to venlafaxine XR for four weeks, i.e. days 29-56). The primary outcome was remission (HAMD-17 ≤ 7) after 8 weeks of treatment as assessed by blinded raters. Remission rates were 24% for EMC and 16% for TAU, which was not significantly different (p = 0.2056). Sensitivity analyses for the primary and secondary effectiveness endpoints consistently showed favorable results for patients randomized to EMC. The results confirm data from post-hoc analyses of clinical trials showing that early non-improvement identifies patients who likely need alternate interventions. However, the herein used two-step switch/augmentation strategy for this risk group was not more effective than the control intervention. Alternate strategies and other design aspects are discussed in order to support researchers addressing the same research question. PMID:26899588

  8. Combining antidepressants

    PubMed Central

    DUNNER, David L

    2014-01-01

    Summary Treatment-resistant depression is a common problem encountered by psychiatrists. These patients are often difficult to treat effectively. Strategies for addressing patients with treatment-resistant depression include changing medications, adding another antidepressant (antidepressant polypharmacy), and augmenting treatment with a non-antidepressant. PMID:25642112

  9. Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings

    PubMed Central

    Verstuyft, Céline; Corruble, Emmanuelle; Perlemuter, Gabriel; Colle, Romain

    2016-01-01

    Background Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. Aim To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. Methods We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. Results An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. Conclusion These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment. PMID:27171561

  10. Non-response in a nationwide follow-up postal survey in Finland: a register-based mortality analysis of respondents and non-respondents of the Health and Social Support (HeSSup) Study

    PubMed Central

    Koskenvuo, Karoliina; Sillanmäki, Lauri; Vahtera, Jussi; Korkeila, Katariina; Kivimäki, Mika; Mattila, Kari J; Virtanen, Pekka; Sumanen, Markku; Rautava, Päivi; Koskenvuo, Markku

    2012-01-01

    Objective To examine difference in mortality between postal survey non-respondents and respondents. Design A prospective cohort study with baseline survey in 1998 and comprehensive linkage to national mortality registers until 2005, the Health and Social Support study. Setting A population-based postal survey of the working-aged population in Finland in 1998. Participants The original random sample comprised 64 797 working-aged individuals in Finland (20–24, 30–34, 40–44, 50–54 years of age; 32 059 women and 32 716 men), yielding 25 898 (40.0%) responses in the baseline postal survey in 1998. Primary outcome measure Registry-based primary causes of death encoded with the International Classification of Diseases (ICD-10). Results In women, HR for total mortality was 1.75 (95% CI 1.40 to 2.19) times higher among the non-respondents compared with the respondents. In men, non-response was associated with a 1.41-fold (1.21–1.65) excess risk of total mortality. Non-response associated in certain age groups with deaths due to diseases in women and with deaths due to external causes in men. The most prominent excess mortality was seen for total mortality for both genders and for mortality due to external causes among men. Conclusions Postal surveys result in slight underestimation of illness prevalence. PMID:22422917

  11. In vivo studies of effects of antidepressants on parotid salivary secretion in the rat.

    PubMed

    Johnsson, Martin; Winder, Michael; Zawia, Hana; Lödöen, Ida; Tobin, Gunnar; Götrick, Bengt

    2016-07-01

    Tricyclic antidepressants (TCA) are well-known xerogenic drugs, while antidepressants such as selective serotonin reuptake inhibitors (SSRI) are considered less xerogenic. The antimuscarinic effect of the TCAs has been considered to be the principal mechanism causing a dry mouth. Although the muscarinic receptor is commonly targeted by xerogenic pharmaceuticals, the salivation reflex arc may be affected at other levels as well. We currently wondered whether or not antidepressants exert an inhibition of the salivary reflex not only at the glandular level but at a central level as well. In this study, the effects of a TCA (clomipramine), a SSRI (citalopram) and a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine) were examined on reflex- (0.5M citric acid applied on the tongue) and methacholine-evoked salivary secretion. While all three compounds inhibited citric acid-evoked secretion (-40 to -60% at 5mg/kg i.v. of the antidepressants), only clomipramine inhibited methacholine-evoked secretion (-30% at 5mg/kg i.v.). On the contrary, both citalopram and venlafaxine increased the methacholine-evoked secretion (+44 to 49%). This was particularly obvious for the salivary protein output (>200%). In the presence of α- and β-adrenoceptor antagonists, the citalopram- and venlafaxine-induced increases were reduced. Thus, antidepressants irrespective of type may exert xerogenic effects by inhibiting the salivary reflex in the central nervous system. However, while TCAs may also hamper the secretory response by antimuscarinic effects, the SSRI and the SNRI groups of pharmaceuticals seem to lack this additional xerogenic mechanism indicating a better therapeutic profile and better opportunities for pharmacological treatment of drug-induced xerostomia. PMID:27023402

  12. Research on antidepressants in India

    PubMed Central

    Avasthi, Ajit; Grover, Sandeep; Aggarwal, Munish

    2010-01-01

    Data suggests that antidepressants are useful in the management of depressive disorders, anxiety disorders, sexual dysfunction, eating disorders, impulse control disorders, enuresis, aggression and some personality disorders. Research focusing on the usefulness of antidepressants in India has more or less followed the trends seen in the West. Most of the studies conducted in India have evaluated various antidepressants in depression. In this article, we review studies conducted in India on various antidepressants. The data suggests that antidepressants have been evaluated mainly in the acute phase treatment and rare studies have evaluated the efficacy in continuation phase treatment. PMID:21836704

  13. A Longitudinal Functional Neuroimaging Study in Medication-Naïve Depression after Antidepressant Treatment

    PubMed Central

    Kawasaki, Shingo; Pu, Shenghong; Iwanami, Akira; Hirano, Jinichi; Nakagome, Kazuyuki; Mimura, Masaru

    2015-01-01

    Recent studies have indicated the potential clinical use of near infrared spectroscopy (NIRS) as a tool in assisting the diagnosis of major depressive disorder (MDD); however, it is still unclear whether NIRS signal changes during cognitive task are state- or trait-dependent, and whether NIRS could be a neural predictor of treatment response. Therefore, we conducted a longitudinal study to explore frontal haemodynamic changes following antidepressant treatment in medication-naïve MDD using 52-channel NIRS. This study included 25 medication-naïve individuals with MDD and 62 healthy controls (HC). We performed NIRS scans before and after antidepressant treatment and measured changes of [oxy-Hb] activation during a verbal fluency task (VFT) following treatment. Individuals with MDD showed significantly decreased [oxy-Hb] values during a VFT compared with HC in the bilateral frontal and temporal cortices at baseline. There were no [oxy-Hb] changes between pre- and post-antidepressant treatment time points in the MDD cohort despite significant improvement in depressive symptoms. There was a significant association between mean [oxy-Hb] values during a VFT at baseline and improvement in depressive symptoms following treatment in the bilateral inferior frontal and middle temporal gyri in MDD. These findings suggest that hypofrontality response to a VFT may represent a potential trait marker for depression rather than a state marker. Moreover, the correlation analysis indicates that the NIRS signals before the initiation of treatment may be a biological marker to predict patient’s clinical response to antidepressant treatment. The present study provides further evidence to support a potential application of NIRS for the diagnosis and treatment of depression. PMID:25786240

  14. Use of a 12 months' self-referral reminder to facilitate uptake of bowel scope (flexible sigmoidoscopy) screening in previous non-responders: a London-based feasibility study

    PubMed Central

    Kerrison, Robert S; McGregor, Lesley M; Marshall, Sarah; Isitt, John; Counsell, Nicholas; Wardle, Jane; von Wagner, Christian

    2016-01-01

    Background: In March 2013, NHS England extended its national Bowel Cancer Screening Programme to include ‘one-off' Flexible Sigmoidoscopy screening (NHS Bowel Scope Screening, BSS) for men and women aged 55. With less than one in two people currently taking up the screening test offer, there is a strong public health mandate to develop system-friendly interventions to increase uptake while the programme is rolling out. This study aimed to assess the feasibility of sending a reminder to previous BSS non-responders, 12 months after the initial invitation, with consideration for its potential impact on uptake. Method: This study was conducted in the ethnically diverse London Boroughs of Brent and Harrow, where uptake is below the national average. Between September and November 2014, 160 previous non-responders were randomly selected to receive a reminder of the opportunity to self-refer 12 months after their initial invitation. The reminder included instructions on how to book an appointment, and provided options for the time and day of the appointment and the gender of the endoscopist performing the test. To address barriers to screening, the reminder was sent with a brief locally tailored information leaflet designed specifically for this study. Participants not responding within 4 weeks were sent a follow-up reminder, after which there was no further intervention. Self-referral rates were measured 8 weeks after the delivery of the follow-up reminder and accepted as final. Results: Of the 155 participants who received the 12 months' reminder (returned to sender, n=5), 30 (19.4%) self-referred for an appointment, of which 24 (15.5%) attended and were successfully screened. Attendance rates differed by gender, with significantly more women attending an appointment than men (20.7% vs 8.8%, respectively; OR=2.73, 95% CI=1.02–7.35, P=0.05), but not by area (Brent vs Harrow) or area-level deprivation. Of the 30 people who self-referred for an appointment, 27 (90

  15. CNS effects of citalopram, a new serotonin inhibitor antidepressant (a quantitative pharmaco-electroencephalography study).

    PubMed

    Itil, T M; Menon, G N; Bozak, M M; Itil, K Z

    1984-01-01

    Citalopram, a new phthalane derivative and a specific serotonin re-uptake inhibitor in animal pharmacological tests, was evaluated in a double-blind, crossover, quantitative pharmaco-EEG (QPEEGTM) study in healthy human volunteers. The CNS effects of citalopram are linear, dose- and time-related, can statistically be differentiated from placebo, and indicate a rapid onset of effects with short duration. According to the Computer Data Bank, citalopram has a mode of action similar to mood elevators (antidepressants) with fewer sedative properties. Thus the therapeutic action of citalopram is predicted to be similar to desipramine and protriptyline from the tricyclics, and fluvoxamine from non-tricyclics. According to data bank assessment, it is hypothesized that the single antidepressant dose of citalopram is to be more than 25 mg, which should be given t.i.d. in clinical trials. PMID:6592676

  16. Primary adherence to antidepressant prescriptions in primary health care: a population-based study in Sweden

    PubMed Central

    Freccero, Carl; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2016-01-01

    Background Medical adherence is important in the treatment of depression. Primary medical adherence, i.e. patients collecting their newly prescribed medications from pharmacies, is very different depending on the drug prescribed Objective To assess the rate of primary medical adherence in patients prescribed antidepressants and to identify characteristics that make patients less likely to pick up prescriptions. Methods An observational study was performed using primary health care data from Sweden on patients who were prescribed antidepressants. Univariate and multivariate logistic regression was used to determine differences in pick-up rate according to patient characteristics. Main outcome Pick-up rate, defined as collection of a prescription within 30 days. Results A total of 11 624 patients received an antidepressant prescription during the study period, and the overall pick-up rate was 85.1%. The pick-up rate differed according to country of birth: individuals born in the Middle East and other countries outside Europe had lower primary medical adherence than Swedes, with adjusted odds ratios (ORs) of 0.58 and 0.67, respectively. Patients at ages 64–79 years had a higher pick-up rate compared with those aged 25–44 years (OR 1.71). Divorced patients had a lower rate compared with married patients (OR 0.80). Conclusion Immigrants from the Middle East and other countries outside Europe and younger and divorced patients had lower primary medical adherence, which calls for clinical attention and preventive measures. Key pointsPrimary medical adherence is important in the treatment of depression.Are patient characteristics associated with primary medical adherence?The overall primary medical adherence rate was 85%.The rate differed by country of birth, age at diagnosis of depression, and marital status.Clinical attention is needed in patients who do not pick up their antidepressants. PMID:26828942

  17. A study on evalution of antidepressant effect of imipramine adjunct with Aswagandha and Bramhi.

    PubMed

    Maity, T; Adhikari, A; Bhattacharya, K; Biswas, S; Debnath, P K; Maharana, C S

    2011-12-01

    Depressive disorders increase the risks of self-harm or even suicide in patients. Indigenous drugs are being tried to treat such patient along with conventional antidepressant drugs. This study was planned to investigate the antidepressant action of Ashwagandha and Bramhi and also to confirm its efficacy in the behavioural despair animal model of depression. Normal saline as control (5 ml/kg), Imipramine as standard (16, 32, 64 mg/ kg) and Ashwagandha (50, 100, 150 mg/kg), Bramhi (20, 40, 80 mg/kg) as test drugs were introduced to the albino rats weighing between 200-250 gm for 2 weeks, 1 hr before electric shock in Learned helplessness test (LHT) and swimming in Forced swimming test (FST). Effects of individual drugs as well as their combination were evaluated. Avoidance response, escape failure and immobility period in case of Imipramine and Ashwagandha showed highly significant (p < 0.01) result on individual use. There was no significant result in case of Bramhi used alone except in escape failure and immobility period (FST), where at higher doses it showed significant (p < 0.01) result. But combination of Bramhi and Ashwagandha in low doses with low dose of Imipramine gave a highly significant result (p < 0.01) in all the parameters. Ashwagandha had significant antidepressant action, but Bramhi had not when used alone. Combination of these two indigenous drug with Imipramine showed high efficacy in animal model. PMID:23016473

  18. Effects of Antidepressant Treatment on Sexual Arousal in Depressed Women: A Preliminary fMRI Study

    PubMed Central

    Yang, Jong-Chul; Park, Jong-Il; Kim, Gwang-Won; Eun, Sung-Jong; Lee, Moo-Suk; Han, Kyung-Lae; Chae, Jeong-Ho

    2012-01-01

    Objective There was a recent study to explore the cerebral regions associated with sexual arousal in depressed women using functional magnetic resonance imaging (fMRI). The purpose of this neuroimaging study was to investigate the effects of antidepressant treatment on sexual arousal in depressed women. Methods Seven depressed women with sexual arousal dysfunction (mean age: 41.7±13.8, mean scores of the Beck Depression Inventory (BDI) and the 17-item Hamilton Rating Scale for Depression (HAMD-17): 35.6±7.1 and 34.9±3.1, respectively) and nine healthy women (mean age: 40.3±11.6) underwent fMRI before and after antidepressant treatment. The fMRI paradigm contrasted a 1 minute rest period viewing non-erotic film with 4 minutes of sexual stimulation viewing an erotic video film. Data were analyzed by SPM 2. The relative number of pixels activated in each period was used as an index of activation. All depressed women were treated with mirtazapine (mean dosage: 37.5 mg/day) for 8 to 10 weeks. Results Levels of brain activity during sexual arousal in depressed women significantly increased with antidepressant treatment (p<0.05) in the regions of the hypothalamus (3.0% to 11.2%), septal area (8.6% to 27.8%) and parahippocampal gyrus (5.8% to 14.6%). Self-reported sexual arousal during visual sexual stimulation also significantly increased post-treatment, and severity of depressive symptoms improved, as measured by the BDI and HAMD-17 (p<0.05). Conclusion These results show that sexual arousal dysfunction of depressed women may improve after treatment of depression, and that this improvement is associated with increased activation of the hypothalamus, septal area, and parahippocampal gyrus during sexual arousal. PMID:23251203

  19. Pharmacogenetics of antidepressant response.

    PubMed

    Keers, Robert; Aitchison, Katherine J

    2011-01-01

    There is substantial interindividual variation in response to antidepressants. Family and twin studies suggest that genetic variation may, at least in part, explain these differences. Pharmacogenetic research attempts to identify the genetic variants associated with antidepressant response to both understand the mechanism of action of pharmacotherapies and to predict outcome. Genes implicated in the pharmacokinetics or pharmacodyamics of antidepressants have been shown to predict response; however, the failure of some findings to replicate has been disappointing. More recent hypothesis-free approaches have identified novel candidates for antidepressant response. However, results have been considerably modest and suggest that treatment outcome is determined by multiple genetic variants of small effect. The small effect sizes of genetic variants and heterogeneity between studies have significantly hindered attempts to find robust genetic predictors of response to antidepressants. To allow the direct comparison of findings, future pharmacogenetic studies should employ standardized methodology and consider using intermediate phenotypes of response, such as neurogenesis, that may more closely reflect the mechanism of action of antidepressants. PMID:21158559

  20. Study protocol for the randomised controlled trial: Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study)

    PubMed Central

    2013-01-01

    Background Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake inhibitors to increase forebrain 5-hydroxytryptamine, while co-administration of antiglucocorticoids has the opposite effect. A Cochrane review suggests that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD and includes a pilot study of the cortisol synthesis inhibitor, metyrapone. The Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study) is a multicentre randomised placebo controlled trial of metyrapone augmentation of serotonergic antidepressants in a large population of patients with TRD in the UK National Health Service. Methods/design Patients with moderate to severe treatment refractory Major Depression aged 18 to 65 will be randomised to metyrapone 500 mg twice daily or placebo for three weeks, in addition to on-going conventional serotonergic antidepressants. The primary outcome will be improvement in Montgomery-Åsberg Depression Rating Scale score five weeks after randomisation (i.e. two weeks after trial medication discontinuation). Secondary outcomes will include the degree of persistence of treatment effect for up to 6 months, improvements in quality of life and also safety and tolerability of metyrapone. The ADD Study will also include a range of sub-studies investigating the potential mechanism of action of metyrapone. Discussion Strengths of the ADD study include broad inclusion criteria meaning that the sample will be representative of patients with TRD treated within the UK National Health

  1. Childhood Predictors of Use and Costs of Antidepressant Medication by Age 24 Years: Findings from the Finnish Nationwide 1981 Birth Cohort Study

    ERIC Educational Resources Information Center

    Gyllenberg, David; Sourander, Andre; Niemela, Solja; Helenius, Hans; Sillanmaki, Lauri; Ristkari, Terja; Piha, Jorma; Kumpulainen, Kirsti; Tamminen, Tuula; Moilanen, Irma; Almqvist, Fredrik

    2011-01-01

    Objective: Prior studies on antidepressant use in late adolescence and young adulthood have been cross-sectional, and prospective associations with childhood psychiatric problems have not been examined. The objective was to study the association between childhood problems and lifetime prevalence and costs of antidepressant medication by age 24…

  2. Factors Associated with the Combined Use of Antidepressants and Benzodiazepines in Major Depression: A Case-Control Study.

    PubMed

    Fulone, Izabela; Silva, Marcus T; Lopes, Luciane C

    2016-09-01

    The aim of this study was to identify the factors associated with the combined use of antidepressants and benzodiazepines (BDZs) in patients with major depression. We conducted a case-control study in the public health service of the city of São Paulo, Brazil. The participants were all patients being treated with antidepressants, who were diagnosed with major depression. Patients who received a combination of antidepressants and BDZs were classified as cases, and those who used only antidepressants, as controls. Data were obtained from a pharmacy database, medical records and interviews with the healthcare team. The association of predisposing factors for combined therapy was analysed using logistic regression analysis, and the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of the 1355 users of antidepressants, 265 had major depression, of whom 138 were cases and 127 were controls. The factors associated with combined use were age older than 35 years (OR 2.2, 95% CI 1.0-4.7), absence of comorbidities (OR 2.3, 95% CI 1.4-4.1) and no use of other drugs (OR 1.9, 95% CI 1.1-3.3). Patients with combined use were more likely to exhibit inadequate prescribing, including inappropriate antidepressants (OR 4.7, 95% CI 2.2-9.9), inadequate dosages (OR 3.62, 95% CI 1.4-9.6) and/or a non-recommended duration (OR 66.6, 95% CI 18.4-240.7). The factors identified showed the groups most susceptible to combined use in this population, who in turn are more likely to receive inappropriate prescriptions. PMID:26998968

  3. GC-MS-based metabolomic study on the antidepressant-like effects of diterpene ginkgolides in mouse hippocampus.

    PubMed

    Liang, Zihong; Bai, Shunjie; Shen, Peng; Hu, Qingchuan; Wang, Xingfa; Dong, Meixue; Wang, Wei; Li, Juan; Cheng, Ke; Zhang, Shuxiao; Zou, Dezhi; Han, Yu; Wang, Haiyang; Xie, Peng

    2016-11-01

    Ginkgo biloba extract (GBE), including EGb-761, have been suggested to have antidepressant activity based on previous behavioral and biochemical analyses. However, because GBE contain many constituents, the mechanisms underlying this suggested antidepressant activity are unclear. Here, we investigated the antidepressant-like effects of diterpene ginkgolides (DG), an important class of constituents in GBE, and studied their effects in the mouse hippocampus using a GC-MS-based metabolomics approach. Mice were randomly divided into five groups and injected daily until testing with 0.9% NaCl solution, one of three doses of DG (4.06, 12.18, and 36.54mg/kg), or venlafaxine. Sucrose preference (SPT) and tail suspension (TST) tests were then performed to evaluate depressive-like behaviors in mice. DG (12.18 and 36.54mg/kg) and venlafaxine (VLX) administration significantly increased hedonic behavior in mice in the SPT. DG (12.18mg/kg) treatment also shortened immobility time in the TST, suggestive of antidepressant-like effects. Significant differences in the metabolic profile in the DG (12.18mg/kg) compared with the control or VLX group indicative of an antidepressant-like effect were observed using multivariate analysis. Eighteen differential hippocampal metabolites were identified that discriminated the DG (12.18mg/kg) and control groups. These biochemical changes involved neurotransmitter metabolism, oxidative stress, glutathione metabolism, lipid metabolism, energy metabolism, and kynurenic acid, providing clues to the therapeutic mechanisms of DG. Thus, this study showed that DG has antidepressant-like activities in mice and shed light on the biological mechanisms underlying the effects of diterpene ginkgolides on behavior, providing an important drug candidate for the treatment of depression. PMID:27498146

  4. The effect of regulatory advisories on maternal antidepressant prescribing, 1995-2007: an interrupted time series study of 228,876 pregnancies.

    PubMed

    Bobo, William V; Epstein, Richard A; Hayes, Rachel M; Shelton, Richard C; Hartert, Tina V; Mitchel, Ed; Horner, Jeff; Wu, Pingsheng

    2014-02-01

    The purpose of this study was to assess whether antidepressant prescribing during pregnancy decreased following release of U.S. and Canadian public health advisory warnings about the risk of perinatal complications with antidepressants. We analyzed data from 228,876 singleton pregnancies among women (aged 15-44 years) continuously enrolled in Tennessee Medicaid with full pharmacy benefits (1995-2007). Antidepressant prescribing was determined through outpatient pharmacy dispensing files. Information on sociodemographic and clinical factors was obtained from enrollment files and linked birth certificates. An interrupted time series design with segmented regression analysis was used to quantify the impact of the advisory warnings (2002-2005). Antidepressant prescribing rates increased steadily from 1995 to 2001, followed by sharper increases from 2002 to late 2004. Overall antidepressant prescribing prevalence was 34.51 prescriptions [95 % confidence interval (CI) 33.37-35.65] per 1,000 women in January 2002, and increased at a rate of 0.46 (95 % CI 0.41-0.52) prescriptions per 1,000 women per month until the end of the pre-warning period (May 2004). During the post-warning period (October 2004-June 2005), antidepressant prescribing decreased by 1.48 (95 % CI 1.62-1.35) prescriptions per 1,000 women per month. These trends were observed for both selective serotonin reuptake inhibitors (SSRI) and non-SSRI antidepressants, although SSRI prescribing decreased at a greater rate. We conclude that antidepressant prescribing to pregnant women in Tennessee Medicaid increased from 1995 to late 2004. U.S. and Canadian public health advisories about antidepressant-associated perinatal complications were associated with steady decreases in antidepressant prescribing from late 2004 until the end of the study period, suggesting that the advisory warnings were impactful on antidepressant prescribing in pregnancy. PMID:24196827

  5. Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD

    PubMed Central

    Ehlken, C; Jungmann, S; Böhringer, D; Agostini, H T; Junker, B; Pielen, A

    2014-01-01

    Background Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD. Methods and materials A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity. Results Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences. Conclusions An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies. PMID:24722504

  6. Using Multiple Imputation to Assign Pesticide Use for Non-Responders in the Follow-Up Questionnaire in the Agricultural Health Study

    EPA Science Inventory

    The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and...

  7. Augmenting Antidepressant Medication Treatment of Depressed Women with Emotionally Focused Therapy for Couples: A Randomized Pilot Study

    ERIC Educational Resources Information Center

    Denton, Wayne H.; Wittenborn, Andrea K.; Golden, Robert N.

    2012-01-01

    This is the first study to evaluate adding emotionally focused therapy for couples (EFT) to antidepressant medication in the treatment of women with major depressive disorder and comorbid relationship discord. Twenty-four women and their male partners were randomized to 6 months of medication management alone (MM) or MM augmented with EFT (MM +…

  8. [Antidepressive agents and memory].

    PubMed

    Danion, J M

    1993-07-01

    It is important that antidepressants, now increasingly used in ambulatory treatment of many patients, should not be detrimental to cognition and memory. It is difficult to assess these effects. One must make a distinction between the direct effects of antidepressants on cognition, related to their intrinsic properties, and indirect effects secondary to mood improvement. The tests used in studies essentially focus on psychomotricity and do not accurately evaluate the effects on cognition itself. Indeed, there are different kinds of memory which would require specific investigations. It has nevertheless been demonstrated that acute administration of sedative antidepressants with a marked anticholinergic component are detrimental to the memory processes. However, following prolonged administration, tolerance may develop within 1 to 3 weeks. Some antidepressants, however, especially serotonergics, do not cause any disturbances of memory. In depressed subjects, it seems that, overall, long-term antidepressant treatment improves cognitive functions. This effect is due to the combination of drug tolerance and of the indirect effects secondary to mood improvement. Elderly subjects appear to be more sensitive to the detrimental effects on memory and they develop drug tolerance more slowly. Lastly, two studies have reported that serotonin re-uptake inhibitors might have beneficial effects on memory disorders secondary to acute or chronic alcohol abuse. PMID:8281908

  9. Antidepressant Response in Patients With Major Depression Exposed to NSAIDs: A Pharmacovigilance Study

    PubMed Central

    Gallagher, Patience J.; Castro, Victor; Fava, Maurizio; Weilburg, Jeffrey B.; Murphy, Shawn N.; Gainer, Vivian S.; Churchill, Susanne E.; Kohane, Isaac S.; Iosifescu, Dan V.; Smoller, Jordan W.; Perlis, Roy H.

    2013-01-01

    Objective It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system. Method Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed. Results NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21–2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables. Conclusions These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding. PMID:23032386

  10. A prospective observational study to evaluate safety reporting of antidepressants at a tertiary care hospital in India

    PubMed Central

    Lucca, Jisha M.; Madhan, Ramesh; Gurumurthy, Parthasarathi; Dushad, Ram

    2014-01-01

    Objective: This prospective observational study was carried out to identify the prevalence and Severity of ADRs of antidepressant in a tertiary care teaching hospital. Materials and Methods: Patients prescribed with at least one antidepressant were randomly selected and monitored for adverse drug reactions (ADRs), irrespective of their age and gender. Results: Of the 401 patients who received antidepressants, 170 patients (42.39%) experienced 204 ADRs. Selective serotonin receptor inhibitors (SSRIs) [110 (53.92)] was the most common therapeutic class of drugs associated with ADRs. Gastrointestinal system [54 (26.47)] was most commonly affected system organ class. Dry mouth (n = 30) and diaphoresis (n = 21) were the most frequently reported ADRs. As assessed by the World Health organization (WHO) probability scale, 61% of the ADRs were ‘probable’ causality. Among all the ADRs, 22.54% (46) were preventable. Majority of the ADRs [(n = 184) 90.17%] were ‘mild’ in their severity. Conclusion: In this study, incidence of adverse reaction to antidepressants was 42.3% were the most comman SSRI inplicated drug group for the ADRs. PMID:25298586

  11. Neuronal and immunological basis of action of antidepressants in chronic pain - clinical and experimental studies.

    PubMed

    Mika, Joanna; Zychowska, Magdalena; Makuch, Wioletta; Rojewska, Ewelina; Przewlocka, Barbara

    2013-01-01

    The current knowledge of the pharmacological actions of the tricyclic antidepressants (TCAs) has slowly evolved through their over 40-year history. Chronic pain represents one of the most important public health problems, and antidepressants are an essential part of the therapeutic strategy in addition to classical analgesics. This article reviews the available evidence on the efficacy and safety of antidepressants in chronic pain conditions; namely, headaches, low back pain, fibromyalgia, cancer pain and especially neuropathic pain. TCAs are traditionally the main type of depression medication used to treat chronic pain. Recently, new antidepressants were introduced into clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs that are effective for chronic pain belong to the tetracyclic antidepressants (TeCAs) group (amoxapine, maprotiline), the serotonin and noradrenaline reuptake inhibitors (SNRIs) group (duloxetine, venlafaxine, milnacipran) and the atypical antidepressants group (bupropion, trazodone, mirtazapine, nefazodone). In this review, we present the available publications on TCAs (amitriptyline, doxepin, imipramine, desipramine, nortriptyline), TeCAs (amoxapine, maprotiline), selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluoxetine, paroxetine), SNRIs (duloxetine, venlafaxine, milnacipran) and atypical antidepressants (bupropion) for the treatment of neuropathic pain. We also review analgesics acting as both opioid receptor agonists and also acting as aminergic reuptake inhibitors. Existing data are insufficient to conclude which of these new classes of antidepressants has the best clinical profile and will be the most effective in the treatment of neuropathic pain; in addition, a lower incidence of side effects should be considered. Increased experimental and translational research is a key for further improvement of the treatment of chronic pain with antidepressants. However

  12. Repeated vaccinations do not improve specific immune defenses against Hepatitis B in non-responder health care workers.

    PubMed

    Zaffina, Salvatore; Marcellini, Valentina; Santoro, Anna Paola; Scarsella, Marco; Camisa, Vincenzo; Vinci, Maria Rosaria; Musolino, Anna Maria; Nicolosi, Luciana; Rosado, M Manuela; Carsetti, Rita

    2014-12-01

    Hepatitis B is a major infectious occupational hazard for health care workers and can be prevented with a safe and effective vaccine. The serum titer of anti-HBsAg antibodies is the most commonly used correlate of protection and post-vaccination anti-HBsAg concentrations of ≥ 10 mIU/ml are considered protective. Subjects with post-vaccination anti-HBsAg titers of <10 mIU/ml 1-6 months post-vaccination, who tested negative for HBsAg and anti-HBc, are defined as non-responders. The question of whether non-responders should be repeatedly vaccinated is still open. The aim of the study was to (i) evaluate the distribution of lymphocyte subpopulations and the percentage of HBsAg-specific memory B cells in responders and non-responders (ii) assess whether non-responders can be induced to produce antibodies after administration of a booster dose of vaccine (iii) determine whether booster vaccination increases the number of specific memory B cells in non-responders. Combining flow-cytometry, ELISPOT and serology we tested the integrity and function of the immune system in 24 health care workers, confirmed to be non-responders after at least three vaccine injections. We compared the results with those obtained in 21 responders working in the same institution. We found that the great majority of the non-responders had a functional immune system and a preserved ability to respond to other conventional antigens. Our most important findings are that the frequency of HBsAg-specific memory B cells is comparable in non-responders and controls and that booster immunization does not lead either to antibody production or memory B cell increase in non-responders. PMID:25444815

  13. Triptan nonresponder studies: implications for clinical practice.

    PubMed

    Dodick, David W

    2005-02-01

    The maximum absolute response rate with oral triptans, as measured in clinical trials by the incidence of relief from migraine pain at 2 hours after taking medication, is approximately 70%. Therefore around 30% of patients fail to respond to a particular triptan. Nonresponse is likely to be due to a variety of factors, including low and inconsistent absorption, use of the medication late in an attack, inadequate dosing, and variability in individual response. Evidence from recent clinical trials, however, confirms the common clinical observation that patients with a poor response to one triptan can benefit from subsequent treatment with a different triptan. Two-hour pain-relief rates of 25% to 81% using alternative triptans (naratriptan, almotriptan, eletriptan, zolmitriptan, and rizatriptan) have been reported in patients who were described as poor responders to sumatriptan. Physicians should remain vigilant in assessing the response to acute therapy and take advantage of simple clinical questionnaires that have been developed to facilitate the recognition of those patients who require and may benefit from a change in acute therapy. PMID:15705122

  14. Antidepressants and Suicidality.

    PubMed

    Brent, David A

    2016-09-01

    We review the evidence that antidepressants either increase or decrease the risk for suicidal ideation and behavior in adolescents. Meta-analyses of randomized clinical trials (RCTs) indicate a small increased risk for suicidal events in adolescents and young adults, but a protective effect in older adults. In contrast, pharmacoepidemiologic studies show a protective effect across the life span. Explanations for occurrence of suicidal events in younger patients and for the apparent contradiction between RCT and pharmacoepidemiologic studies are offered. Guidance for clinicians is provided on explaining the risk-benefit ratio of antidepressants and how to monitor and attenuate for suicidal risk. PMID:27514302

  15. 5-HTR1A and 5-HTR2A genetic polymorphisms and SSRI antidepressant response in depressive Chinese patients

    PubMed Central

    Dong, Zai-Quan; Li, Xi-Rong; He, Lin; He, Guang; Yu, Tao; Sun, Xue-Li

    2016-01-01

    Objective Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs. Methods Two hundred and ninety patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder were involved in this study. SSRIs (fluoxetine, paroxetine, citalopram, or sertraline) were selected randomly for treatment. The Hamilton Rating Scale for Depression was used to evaluate the antidepressant effect. To assess 5-HTR gene variabilities, two single-nucleotide polymorphisms in 5-HTR1A (rs1364043 and rs10042486) and three in 5-HTR2A (rs6311, rs6313, and rs17289304) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Sequenom MassARRAY Analyzer 4 system. Results There were 220 responders and 70 nonresponders (120 remissioners and 170 nonremissioners) after 6 weeks of treatment. We found no association between any of the five 5-HTR1A and 5-HTR2A gene polymorphisms and antidepressant drug response or remission (P>0.05). It is worth mentioning that TT genotype frequency of rs10042486 was significantly different from the CT genotype frequency between responders and nonresponders, although the significance was not maintained after correcting for multiple testing. Conclusion Thus, 5-HTR1A and 5-HTR2A gene polymorphisms may not play an important role in antidepressant drug response or remission. PMID:27445478

  16. Study of a mechanism responsible for potential antidepressant activity of EMD 386088, a 5-HT6 partial agonist in rats.

    PubMed

    Jastrzębska-Więsek, Magdalena; Siwek, Agata; Partyka, Anna; Antkiewicz-Michaluk, Lucyna; Michaluk, Jerzy; Romańska, Irena; Kołaczkowski, Marcin; Wesołowska, Anna

    2016-08-01

    It was shown that 5-HT6 receptor agonists can exert pharmacological activity due to various modifications in monoamines' level and metabolism activity in rats' brain structures. This finding was correlated with antidepressant- or anxiolytic-like properties of these compounds. The study was designed to establish a possible mechanism of the antidepressant-like activity of the partial 5-HT6 receptor agonist EMD386088 (5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride) in rats. The concentrations of monoamines (dopamine (DA), noradrenaline (NA), and serotonin (5-HT)) and the rate of their metabolism were measured ex vivo in the brain structures (hippocampus, nucleus accumbens, striatum) using high-performance liquid chromatography (HPLC). The rats were killed after the forced swim test (FST); the collected tissue samples were used to ex vivo experiments. The potency of EMD386088 to blockade dopamine transporter (DAT) was tested in a functional in vitro study. FST was used to assess the involvement of D1- and D2-like receptor subfamilies in antidepressant-like properties of EMD386088. Neurochemical data from ex vivo experiments showed that antiimmobility activity of EMD386088 may be connected with the activation of dopaminergic system, while neither noradrenergic nor serotonergic ones are involved in its effect. EMD386088 also possesses a significant affinity for DAT which may be a mechanism in the abovementioned effect. Behavioral data seem to confirm the importance of dopaminergic system activation in antidepressant-like activity of EMD386088, since this effect, observed in the FST, was abolished by the preferential D1- and D2-like receptor subfamily antagonists SCH23390 and sulpiride, respectively. Dopaminergic system is involved in antidepressant-like activity of EMD386088. PMID:27106213

  17. Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database

    PubMed Central

    Hill, Trevor; Morriss, Richard; Moore, Michael; Arthur, Antony; Hippisley-Cox, Julia

    2016-01-01

    Objective To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression. Design Cohort study. Setting UK general practices contributing to the QResearch primary care database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs. Main outcome measures First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years’ follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables. Results During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years’ follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years’ follow-up, although the risk was significantly increased during the first 28 days of

  18. Antidepressant action via the nitric oxide system: A pilot study in an acute depressive model induced by arginin.

    PubMed

    Yoshino, Yuta; Ochi, Shinichiro; Yamazaki, Kiyohiro; Nakata, Shunsuke; Abe, Masao; Mori, Yoko; Ueno, Shu-ichi

    2015-07-10

    Nitric oxide (NO) may be a neurotransmitter related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces dose-dependent antidepressant-like effects. However, its role in MDD is not yet known. The purpose of our study was to determine if antidepressants improve depression via the NO pathway using an acute depressive rat model induced by L-arginine (AR). Three types of antidepressants were examined, fluoxetine (FLX, 10 mg/kg), milnacipran (MIL, 30 mg/kg), and mirtazapine (MIR, 10 mg/kg), in a depressive model that used AR (750 mg/kg) pretreatment. mRNA expression levels of three NOS subtypes were analyzed by real-time PCR, as well as serum NO levels. Significant increases in iNOS mRNA expression levels were found in brain regions after AR treatment, although the eNOS gene tended to decrease with AR injection. After antidepressant treatment, there were no mRNA expression changes in either nNOS or iNOS. However, eNOS mRNA expression significantly increased with FLX (cerebellum, P=0.011; hippocampus, P=0.011; midbrain, P=0.011; pons, P=0.013; striatum, P=0.011; and thalamus, P<0.001). There was a statistically significant increase in serum NO levels with MIL treatment (P=0.011). We conclude that changes in eNOS mRNA levels in the brain with FLX treatment, and amount of serum NO with MIL treatment may be related to antidepressant effects of both agents, but further experiments are needed to confirm involvement of the NO system in MDD. PMID:26007704

  19. Antidepressants in association with reducing risk of oral cancer occurrence: a nationwide population-based cohort and nested case-control studies

    PubMed Central

    Chung, Chia-Min; Kuo, Tzer-Min; Chiang, Shang-Lun; Wang, Zhi-Hong; Hung, Chung-Chieh; Lane, Hsien-Yuan; Liu, Chiu-Shong; Ko, Ying-Chin

    2016-01-01

    Objectives Several studies suggested that antidepressant use may increase or decrease the risk of cancer occurrence, depending on specific cancer types. The possible carcinogenic effect of antidepressants has received substantial attention; however, evidence remains inconclusive. Here we investigated associations between the use of antidepressants and occurrences of oral cancer (OC). Methods Two million samples were randomly collected from the National Health Insurance Research Database in Taiwan, which covers 98% of the total population (23 million). All patients from2000 to 2009 were followed up. We identified 5103 patients newly diagnosed with OC after antidepressants use in addition to 20,412 non-OC matched subjects and 95,452 unmatched non-OC subjects. Results In nested case control analysis, factors associating with OC, including age [OR = 1.02; 95% confidence interval (CI) = 1.01–1.03) and male (OR = 5.30; 95% CI = 4.92–5.70) were independently associated with increased risk of OC. Based on the functions of antidepressants, antidepressants treatment medications were further classified to investigate risk of OC. Selective serotonin reuptake inhibitors (OR = 0.61; 95% CI = 0.53–0.70) and tricyclic antidepressants (OR = 0.57; 95% CI = 0.52–0.63) were associated with reduced risk of OC. The risk of developing OC among subjects taking antidepressants was less than 26% [hazard ratio (HR) =0.74; 95% CI = 0.68–0.81] in prospective cohort study. The effect of a cumulative duration and dose was a significantly reduced risk of OC. Conclusions The association between antidepressant use and decreasing OC risk were demonstrated by both prospective and nested case–control studies. PMID:26840257

  20. Mechanisms underlying the antidepressant response and treatment resistance

    PubMed Central

    Levinstein, Marjorie R.; Samuels, Benjamin A.

    2014-01-01

    Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance. PMID:25018708

  1. [Driving fitness in therapy with antidepressive drugs].

    PubMed

    Soyka, M; Dittert, S; Gartenmeier, A; Schäfer, M

    1998-04-01

    The driving ability of patients under therapy with antidepressives is seen less restrictive than some years ago. The inhibition of psychomotor performance is of special interest. Some empirical studies point at antidepressives increasing the risk for accidents at least in elderly patients. Different groups of antidepressants apparently show different effects. Tricyclic antidepressants were shown to worsen cognitive and psychomotor performance in some patients while serotonin reuptake inhibitors and some other new antidepressants may cause less behavioral toxicity. Methodological problems in assessing driving ability and some recent findings are discussed. PMID:9587241

  2. Use of tricyclic antidepressants and risk of glioma: a nationwide case–control study

    PubMed Central

    Pottegård, Anton; García Rodríguez, Luis Alberto; Rasmussen, Lotte; Damkier, Per; Friis, Søren; Gaist, David

    2016-01-01

    Background: A protective effect of tricyclic antidepressants (TCAs) against gliomas has been suggested by a small number of studies. We investigated this putative association in a nationwide setting. Methods: Using a case–control design, we identified all patients with histologically verified glioma (cases) in Denmark between 2000 and 2012 and matched these 1 : 20 to population controls. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) for glioma associated with long-term (⩾3 years) use of TCAs. Similar analyses were performed for selective serotonin reuptake inhibitors (SSRIs). Results: We identified 3767 glioma cases and 75 340 population controls. Long-term use of TCAs was inversely associated with risk of glioma (OR 0.72, 95% CI: 0.41–1.25). Long-term SSRI use was not associated with glioma risk (OR 0.93, 95% CI: 0.75–1.16). Conclusions: Our study indicated that long-term use of TCAs may be associated with a reduced risk of glioma, however, the statistical precision was limited. A similar pattern was not observed for use of SSRIs. PMID:27115466

  3. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8.

    PubMed

    Sehgal, Sheikh Arslan; Mannan, Shazia; Ali, Sannia

    2016-01-01

    Charcot-Marie-Tooth (CMT) disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand-receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT. PMID:27226709

  4. Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8

    PubMed Central

    Sehgal, Sheikh Arslan; Mannan, Shazia; Ali, Sannia

    2016-01-01

    Charcot–Marie–Tooth (CMT) disease is an inherited peripheral neuromuscular disorder characterized by length-dependent and progressive degeneration of peripheral nerves, leading to muscular weakness. Research has shown that mutated HSPB8 may be responsible for depression, neurodegenerative disorders, and improper functioning of peripheral nerves, resulting in neuromuscular disorders like CMT. In the current work, a hybrid approach of virtual screening and molecular docking studies was followed by homology modeling and pharmacophore identification. Detailed screening analyses were carried out by 2-D similarity search against prescribed antidepressant drugs with physicochemical properties. LigandScout was employed to ascertain novel molecules and pharmacophore properties. In this study, we report three novel compounds that showed maximum binding affinity with HSPB8. Docking analysis elucidated that Met37, Ser57, Ser58, Trp60, Thr63, Thr114, Lys115, Asp116, Gly117, Val152, Val154, Leu186, Asp189, Ser190, Gln191, and Glu192 are critical residues for ligand–receptor interactions. Our analyses suggested paroxetine as a potent compound for targeting HSPB8. Selected compounds have more effective energy scores than the selected drug analogs. Additionally, site-directed mutagenesis could be significant for further analysis of the binding pocket. The novel findings based on an in silico approach may be momentous for potent drug design against depression and CMT. PMID:27226709

  5. Tricyclic Antidepressants

    NASA Astrophysics Data System (ADS)

    Schmidt, Gary J.

    The use of tricyclic antidepressant drugs is becoming increasingly prevalent for the treatment of depressed patients. It has been suggested that, analogous to many other drug substances, the tricyclic drugs exhibit clinical effectiveness within a defined therapeutic concentration range (1-10). Very recently, both Dito (11) and Orsulak and Schildkraut (12) have summarized the usefulness of measuring serum concentrations of these drugs. These authors suggest that knowledge of the plasma concentrations of these drugs aid the physician in determining patient compliance and initiating the best possible drug treatment.

  6. [Advance in studies on natural antidepressant drugs and cytochrome P450].

    PubMed

    Zhang, Lu; Wang, Fei-hu; Chen, Sai-zhen; Pan, Jian-chun

    2015-03-01

    In the fast pace of modern life and under the heavy work pressure, the prevalence of depression has increased year by year. Meanwhile, the demands for antidepressant drugs have also grown, especially the high-efficiency and low-toxicity natural antidepressant drugs, mainly including polyphenols, flavonoids, organic acids, alkaloids and terpenoids. Cytochrome P450 (CYP450) is a type of enzymes involving oxidative metabolism of drugs in vivo, and can change the pharmacokinetics and efficacy of drugs. Therefore, it is of important significant to define the effect of natural antidepressant drugs on CYP450 in human bodies, in order to improve the rational clinical medication, avoid drug interactions and reduce adverse reactions. PMID:26087541

  7. 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants

    PubMed Central

    Richardson-Jones, Jesse W; Craige, Caryne P; Guiard, Bruno P; Stephen, Alisson; Metzger, Kayla L; Kung, Hank F; Gardier, Alain M; Dranovsky, Alex; David, Denis J; Beck, Sheryl G; Hen, René; Leonardo, E David

    2010-01-01

    Summary Most depressed patients don't respond to their first drug treatment, and the reasons for this treatment resistance remain enigmatic. Human studies implicate a polymorphism in the promoter of the serotonin-1A (5-HT1A) receptor gene in increased susceptibility to depression and decreased treatment response. Here we develop a new strategy to manipulate 5-HT1A autoreceptors in raphe nuclei without affecting 5-HT1A heteroreceptors, generating mice with higher (1A-High) or lower (1A-Low) autoreceptor levels. We show that this robustly affects raphe firing rates, but has no effect on either basal forebrain serotonin levels or conflict-anxiety measures. However, compared to 1A-Low mice, 1A-High mice show a blunted physiological response to acute stress, increased behavioral despair, and no behavioral response to antidepressant, modeling patients with the 5-HT1A risk allele. Furthermore, reducing 5-HT1A autoreceptor levels prior to antidepressant treatment is sufficient to convert non-responders into responders. These results establish a causal relationship between 5-HT1A autoreceptor levels, resilience under stress, and response to antidepressants. PMID:20152112

  8. Depressive Symptoms, Antidepressant Use, and the Incidence of Diabetes in the Black Women’s Health Study

    PubMed Central

    Vimalananda, Varsha G.; Palmer, Julie R.; Gerlovin, Hanna; Wise, Lauren A.; Rosenzweig, James L.; Rosenberg, Lynn; Ruiz-Narváez, Edward A.

    2014-01-01

    OBJECTIVE To assess the relationship of depressive symptoms and use of antidepressants with incident type 2 diabetes in prospective data from a large cohort of U.S. African American women. RESEARCH DESIGN AND METHODS The Black Women’s Health Study (BWHS) is an ongoing prospective cohort study. We followed 35,898 women from 1999 through 2011 who were without a diagnosis of diabetes and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D) in 1999. CES-D scores were categorized as <16, 16–22, 23–32, and ≥33, which reflected increasingly more depressive symptoms. We estimated incidence rate ratios (IRRs) and 95% CIs for incident diabetes using Cox proportional hazards models. The basic multivariable model included age, time period, family history of diabetes, and education. In further models, we controlled for lifestyle factors and BMI. We also assessed the association of antidepressant use with incident diabetes. RESULTS Over 12 years of follow-up, there were 3,372 incident diabetes cases. Relative to CES-D score <16, IRRs (95% CI) of diabetes for CES-D scores 16–22, 23–32, and ≥33 were 1.23 (1.12–1.35), 1.26 (1.12–1.41), and 1.45 (1.24–1.69), respectively, in the basic multivariate model. Multiple adjustment for lifestyle factors and BMI attenuated the IRRs to 1.11 (1.01–1.22), 1.08 (0.96–1.22), and 1.22 (1.04–1.43). The adjusted IRR for antidepressant use was 1.26 (1.11–1.43). Results were similar among obese women. CONCLUSIONS Both depressive symptoms and antidepressant use are associated with incident diabetes among African American women. These associations are mediated in part, but not entirely, through lifestyle factors and BMI. PMID:24784829

  9. Follow up of patients who start treatment with antidepressants: treatment satisfaction, treatment compliance, efficacy and safety

    PubMed Central

    2013-01-01

    Background Measuring satisfaction with treatment has proved useful to ascertain the treatment features that are most important to the patients, and to explain increased treatment compliance. However, there are few studies that relate satisfaction to other clinical or self-perceived health status indicators. Recent studies have shown the close relationship between satisfaction with treatment, treatment compliance, and effectiveness. This study attempts to design and validate a scale to evaluate satisfaction with antidepressant drug therapy, assess treatment compliance (self-reported, validated questionnaire, drug accountability and electronic monitorization system), assess efficacy in reducing depressive symptoms and safety in patients who initiate antidepressant drug therapy, as well as to establish predictors of satisfaction, compliance and effectiveness with these drugs. Methods/design This is an observational longitudinal study with a cohort of adults initiating treatment with antidepressant drugs. A multi-centre study will be performed in which 20 Primary Care practices from Castilla-La Mancha are expected to participate. An initial interview and follow-up visits at 15 days, 1, 3, 6, 9 and 12 months will be conducted with all study participants. 706 subjects will be studied (95% confidence interval, precision ± 3%, expected rate of non-compliance 50%, expected non-responders and lost to follow up rate 15%). The following measurements will be performed: development and validation of a scale of satisfaction with antidepressant therapy, participant and antidepressant characteristics, treatment compliance evaluation (Haynes-Sackett Test, Morisky-Green Test, drug accountability and Medication Event Monitoring System), depression symptom reduction (Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale), observation of adverse effects, and beliefs about treatment (The Beliefs about Medicines Questionnaire). Discussion Antidepressant drugs are

  10. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression

    PubMed Central

    Conway, Charles R.; Chibnall, John T.; Gebara, Marie Anne; Price, Joseph L.; Snyder, Abraham Z.; Mintun, Mark A.; (Bud) Craig, A.D.; Cornell, Martha E.; Perantie, Dana C.; Giuffra, Luis A.; Bucholz, Richard D.; Sheline, Yvette I.

    2014-01-01

    Background Vagus nerve stimulation (VNS) has antidepressant effects in treatment resistant major depression (TRMD); these effects are poorly understood. This trial examines associations of subacute (3 months) and chronic (12 months) VNS with cerebral metabolism in TRMD. Objective 17Fluorodeoxyglucose positron emission tomography was used to examine associations between 12-month antidepressant VNS response and cerebral metabolic rate for glucose (CMRGlu) changes at 3 and 12 months. Methods Thirteen TRMD patients received 12 months of VNS. Depression assessments (Hamilton Depression Rating Scale [HDRS]) and PET scans were obtained at baseline (pre-VNS) and 3/12 months. CMRGlu was assessed in eight a priori selected brain regions (bilateral anterior insular [AIC], orbitofrontal [OFC], dorsolateral prefrontal [DLPFC], and anterior cingulate cortices [ACC]). Regional CMRGlu changes over time were studied in VNS responders (decreased 12 month HDRS by ≥50%) and nonresponders. Results A significant trend (decreased 3 month CMRGlu) in the right DLPFC was observed over time in VNS responders (n = 9; P = 0.006). An exploratory whole brain analysis (Puncorrected = 0.005) demonstrated decreased 3 month right rostral cingulate and DLPFC CMRGlu, and increased 12 month left ventral tegmental CMRGlu in responders. Conclusions/Limitations VNS response may involve gradual (months in duration) brain adaptations. Early on, this process may involve decreased right-sided DLPFC/cingulate cortical activity; longer term effects (12 months) may lead to brainstem dopaminergic activation. Study limitations included: a) a small VNS nonresponders sample (N = 4), which limited conclusions about nonresponder CMRGlu changes; b) no control group; and, c) patients maintained their psychotropic medications. PMID:23485649

  11. Usefulness of interim analyses in portending study results in antipsychotic and antidepressant trials.

    PubMed

    Rabinowitz, J; Werbeloff, N; Mandel, F; De Ridder, F; Schacht, A; Menard, F; Caears, I; Stauffer, V; Kapur, S

    2015-11-01

    It is unknown whether interim analyses portend final study results. Fatigue, pressure to complete trials and recruitment differences may mitigate against this. We examined the similarity of efficacy results of the first and second half of recruited patients to complete trials and explore possible intervening variables. Using data from the NewMeds repository of patient level data from placebo-controlled randomized trials of antipsychotics (AP) (22 studies, n=7056) and antidepressants (AD) (39 studies, n=12,217) we compared treatment effect size (placebo vs. active treatment) of the first and second half of patients recruited in completed trials. We found that in AP studies median difference in treatment effect between cohorts was -0.03, indicating that overall first and second cohorts yielded similar results. In AD studies, median difference between cohorts was 0.04, indicating that overall the second cohort had slightly larger active-placebo-difference. Overall, on average there were minimal differences in effect size between the first and the second cohorts, and in 30 of 39 trials interim results were a good estimate of the results on the 2nd cohort. In AD trials first and second cohort results were more similar when the proportion of patients per study centre and recruitment time of the two cohorts was similar. Results suggest that interim analyses in AD and AP studies may reliably serve to estimate ultimate effects and, at least in AD trials, are more accurate when the same sites are used to a similar extent and recruitment time of the two consequent cohorts is similar. PMID:26256009

  12. Relationship between antidepressant effect and plasma level of nortriptyline. Clinical studies.

    PubMed

    Kragh-Søorensen, P; Hansen, C E; Baastrup, P C

    1976-01-01

    Strong evidence has been found for the assumption that NT inhibits its own antidepressive effect at high, but non toxic plasma levels in patients suffering from endogenous depression. Based on three investigations we will recommend an optimal therapeutic plasma range for NT between 50 and 150 ng NT/ml. PMID:790409

  13. The Association between Antidepressant Medications and Coronary Heart Disease in Brazil: A Cross-Sectional Analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil)

    PubMed Central

    Kemp, Andrew H.; Brunoni, Andre R.; Bittencourt, Marcio S.; Nunes, Maria A.; Benseñor, Isabela M.; Lotufo, Paulo A.

    2015-01-01

    Background: Recent studies have highlighted associations between use of antidepressant medications and coronary heart disease (CHD). Tricyclic antidepressants (TCA) are not recommended in patients with CHD as they may increase morbidity and mortality. However, this class of antidepressants is freely prescribed in public health pharmacies, while access to other classes of antidepressants is restricted in Brazil. Here, we examine the associations between antidepressant use and prevalent CHD in a large cohort from Brazil. Methods: Participants included 14,994 civil servants aged 35–74 years from the baseline assessment of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). CHD (n = 710) included stable angina, myocardial infarction, and coronary revascularization. Univariate (unadjusted) and multivariate (adjusted) logistic regression analyses were conducted to estimate odds ratios and confidence intervals. Results: After full adjustment for covariates, TCA use (n = 156) was associated with a twofold increase in prevalent CHD, relative to non-use (n = 14,076). Additional sensitivity analysis revealed a threefold association for myocardial infarction (OR: 2.96, 95% CI: 1.41–6.21) and coronary revascularization (OR: 2.92, 95% CI: 1.28–6.66). There were no significant associations between antidepressant use and stable angina pectoris. Conclusion: Findings highlight a strong association between TCA use and prevalent CHD. While the cross-sectional design is an important limitation of the present study, findings have important implications for the treatment of cardiac patients in Brazil. PMID:25657993

  14. Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

    PubMed Central

    2011-01-01

    Background After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment. The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode. Methods SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents

  15. Clinical-biochemical correlates of migraine attacks in rizatriptan responders and non-responders.

    PubMed

    Sarchielli, P; Pini, L A; Zanchin, G; Alberti, A; Maggioni, F; Rossi, C; Floridi, A; Calabresi, P

    2006-03-01

    The present study was aimed at verifying the clinical characteristics of a typical attack in 20 migraine patients, 10 responders and 10 non-responders to rizatriptan, and at investigating any differences in the levels of neuropeptides of the trigeminovascular or parasympathetic systems [calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) measured by radioimmunoassay methods in external jugular blood] between responders and non-responders. In all responders to rizatriptan, pain was unilateral, severe, and pulsating, and in five of them at least one sign suggestive of parasympathetic system activation was recorded. Five patients who were non-responders to rizatriptan referred bilateral and non-pulsating pain, even though severe in most of them. CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders (P < 0.0001 and P < 0.002, respectively). In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline. One hour after rizatriptan administration, a decrease in CGRP and NKA levels was evident in the external jugular venous blood of rizatriptan responders, and this corresponded to a significant pain relief and alleviation of accompanying symptoms. VIP levels were also significantly reduced at the same time in the five patients with autonomic signs. After rizatriptan administration, CGRP and NKA levels in non-responder patients showed less significant variations at all time points after rizatriptan administration compared with rizatriptan responders. The present study, although carried out on a limited number of patients, supports recent clinical evidence of increased trigeminal activation associated with a better triptan response in migraine patients accompanied by parasympathetic activation in a subgroup of patients with autonomic signs. In contrast, the poor response seems to be correlated with a

  16. [Prevention of hepatitis B--HLA DR/DQ in HBs Ag nonresponder].

    PubMed

    Ouchi, E; Hoshino, A; Miura, T; Nagahara, N; Kudo, Y; Tamura, M

    1989-11-01

    To evaluate the immunological background in HBs Ag nonresponders against hepatitis B vaccine, the lymphocyte surface marker and HLA-DR/DQ antigen were determined on hospital personnel, 70 males and 256 females, injected hepatitis B vaccine for three times. The vaccine made from the plasma of HBs Ag carriers was injected at the first and second vaccination and recombinant hepatitis B vaccine was injected at the third vaccination. A month after the third vaccination, blood was withdrawn for HBs antigen test by RIA. Border line cases (cut off index 1.0-1.9) are included in nonresponder (cut off index less than 0.9). Both nonresponders and low responders (cut off index 2-49) are more often seen in males than females and high responder (cut off index 50 or more) are seen more often in young females than males. Lymphocyte surface markers were studied by flow cytometry using the following monoclonal antibodies; OKT 3, 4, 8, DR, NK, Ia 1 and B7. No differences between lymphocyte surface markers of nonresponders and responders were noted. HLA-DR/DQ antigens were studied by the cytotoxicity test using Locus DR/DQ, Terasaki Second DR W-60 Tray and using following antibodies; DR 1, DR 2, DRW 15, DR 4, DR 5, DR 7, DR 9, DRW 10, DRW 8, DRW 12, DRW 13, DRW 6, DRW 52, DRW 53, DQW 1, DQW 6, DQW 2, DQW 3, DQW 7 and DQW 4. No significant differences between HLA-DR/DQ of nonresponders and responders were noted. PMID:2601078

  17. Effects of depression and antidepressant medications on hip fracture: A population-based cohort study in Taiwan.

    PubMed

    Cheng, Bi-Hua; Chen, Pau-Chung; Yang, Yao-Hsu; Lee, Chuan-Pin; Huang, Ko-En; Chen, Vincent C

    2016-09-01

    This study was conducted to investigate the effects of depression and antidepressant medications on hip fracture. The database of the Taiwan National Health Insurance with medical records of more than 1,000,000 individuals was searched for patients who had hip fracture with or without depression from 1998 to 2009. Patients with the following conditions were excluded: hip fracture due to cancer or traffic accidents, hip fracture that occurred before the diagnosis of depression, and use of antidepressants before the diagnosis of depression. A matched cohort of 139,110 patients was investigated, including 27,822 (17,309 females; 10,513 males) with depression and 111,288 (69,236 females; 42,052 males) without depression (1:4 randomly matched with age, sex, and index date). Among these patients, 232 (158 females and 74 males) had both hip fracture and depression, and 690 (473 females and 217 males) had hip fracture only. The Cox proportional-hazards regression method was used to determine the effect of depression on hip fracture. The hazard ratio (HR) for each clinical parameter was calculated after adjusting for confounders including sex, age, Charlson comorbidity index, urbanization, osteoporosis, and antidepressants. Results showed that patients with major depressive disorder had a 61% higher incidence of hip fracture than those without depression (HR 1.61, 95% confidence interval [CI] 1.19-2.18, P = 0.002). The risk of hip fracture for patients with less severe depressive disorder (dysthymia or depressive disorder, not otherwise specified) was not statistically higher than that of patients with no depression (HR 1.10, 95% CI = 0.91-1.34, P = 0.327). Among the patients with depression, females had a 49% higher incidence for hip fracture than males (HR 1.49, 95% CI 1.30-1.72, P < 0.001). The incidence of hip fracture also increased with age and Charlson comorbidity index scores. Analyses of both all (139,110) patients and only patients (27,822) with depression

  18. [Antidepressives and antidepressive interactions with other drugs].

    PubMed

    Zavrsnik, Davorka; Spirtović, Selma; Becić, Fahir

    2006-01-01

    During the therapy with antidepressive agents, for the reason of its duration, numerous drug-drug interactions may occur. Antidepressive agents inhibit P450 enzyme activity and interfere with other drug metabolism. Many interactions are acceptable from the clinical point of view, and some are seriously dangerous indicating a need for their better knowledge. The aim of this work is to point out the possible interactions between antidepressive agents and other drugs. PMID:16425539

  19. Antidepressant activity of aspartic acid derivatives.

    PubMed

    Petrov, V I; Sergeev, V S; Onishchenko, N V; Piotrovskii, L B

    2001-04-01

    Antidepressant activity of N-phenyl(benzyl)amino derivatives of aspartic acid was studied on various experimental models of depression. IEM-1770 (30 mg/kg) and IEM-1944 (20 mg/kg) exhibited antidepressant activity after single injection in the forced swimming and tail suspension tests. Antidepressant effect of 14-day administration of these compounds and reference drugs maprotiline (10 mg/kg) and citalopram (10 mg/kg) was confirmed on the model of learned helplessness. PMID:11550022

  20. The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

    PubMed Central

    Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

  1. Antidepressant-induced suicidality: an update.

    PubMed

    Reeves, Roy R; Ladner, Mark E

    2010-08-01

    Evidence suggests that antidepressant treatment may in some cases result in worsening depression and increased risk of suicidality in pediatric and adolescent patients. The United States Food and Drug Administration requires that antidepressants carry a black box warning regarding such a risk in patients up to age 24. Many studies of antidepressant-induced suicidality among adults have also reported an increased risk, while several other investigations involving that population have not supported such a finding. This article provides an update of the controversy surrounding antidepressants as a potential cause of suicidal ideations or behavior. Antidepressant-induced suicidality appears to be an uncommon occurrence but also a legitimate phenomenon. Close monitoring and a follow-up care should be provided for patients after initiation of a new antidepressant. PMID:20553304

  2. Psychodynamic Treatment for Separation Anxiety in a Treatment Nonresponder.

    PubMed

    Busch, Fredric N; Milrod, Barbara L

    2015-10-01

    Separation anxiety, long an area of interest for psychoanalysts, has been included in DSM-5 among general "anxiety disorders" that span across age groups. The syndrome of separation anxiety has been shown to correlate with nonresponse to treatments for anxiety and mood disorders (Milrod et al. 2014). It is therefore of public health importance to develop targeted treatments for this syndrome. Some psychoanalysts have suggested that brief psychoanalytic interventions may be of particular value in addressing separation anxiety. Our clinical work with patients with anxiety disorders with high levels of separation anxiety indicates that they have such intense anger and ambivalence in fraught intimate relationships that they feel stuck and helpless, almost eliminating more positive feelings. This ambivalence and associated unconscious conflicts inevitably emerge in the therapeutic relationship and can threaten to disrupt treatment efforts. We propose a set of focused psychodynamic psychotherapeutic interventions to address separation anxiety, developed as part of Panic-Focused Psychodynamic Psychotherapy-eXtended Range (PFPP-XR; Busch et al. 2012). We present a case from our research study of treatment nonresponders with anxiety disorders and separation anxiety. The patient was successfully treated with PFPP-XR in a 21-session treatment. PMID:26487108

  3. [Antidepressant drugs and breastfeeding].

    PubMed

    Bellantuono, Cesario; Migliarese, Giovanni; Maggioni, Francesca; Imperadore, Giuseppe

    2007-01-01

    The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect. PMID:17345878

  4. A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression

    PubMed Central

    Sugawara, Hiroko; Sakamoto, Kaoru; Harada, Tsuyoto; Shimizu, Satoru; Ishigooka, Jun

    2016-01-01

    Background Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD). Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population. Methods Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups. Results The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation. Conclusion Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder. Among them, comorbidity of anxiety disorders was significantly related to the efficacy for TRD including only major depressive disorder. Additional studies are needed to examine the association between the efficacy of aripiprazole augmentation and bipolarity, and these findings should be validated further in a prospective study. PMID:27274249

  5. The association between use of serotonergic antidepressants and perioperative bleeding during total hip arthroplasty--a cohort study.

    PubMed

    Dall, Michael; Primdahl, Annie; Damborg, Frank; Nymark, Tine; Hallas, Jesper

    2014-09-01

    In vitro studies have shown that selective serotonin reuptake inhibitors inhibit platelet aggregation. It is well documented that SSRIs cause serious gastrointestinal bleeding, but studies on other bleeding manifestations have been equivocal. Our objective was to determine a possible association between use of serotonergic antidepressants (SA) and perioperative bleeding during hip replacements. We conducted a retrospective study between 1 January 2007 and 30 June 2012 among patients that underwent a primary unilateral uncemented total hip arthroplasty (THA). Information was collected on the observed blood loss and the need for blood transfusions among this group. We compared the blood loss between users of SA, users of non-serotonergic antidepressants (NSA) and non-users, while adjusting for potential confounders using multivariate linear regression. We indentified 1318 patients that underwent a THA in the study period. The average volume of surgical bleeding was 350 ml. The adjusted incremental blood loss associated with use of SA and NSA was 93, 95% confidence interval (38-147) ml and -50 (-125 to 25) ml compared with non-use. Only 48 subjects (3.6%) had transfusions. Use of SA was associated with an increased blood loss compared with non-users. The hypothesis that SA impairs haemostasis is supported by these results. PMID:24548749

  6. Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.

    PubMed

    Castro, V M; Kong, S W; Clements, C C; Brady, R; Kaimal, A J; Doyle, A E; Robinson, E B; Churchill, S E; Kohane, I S; Perlis, R H

    2016-01-01

    Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50-1.54 for ASD; 0.97, 95% confidence interval 0.53-1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation. PMID:26731445

  7. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

    PubMed

    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials. PMID:26650973

  8. Switching and stopping antidepressants

    PubMed Central

    Keks, Nicholas; Hope, Judy; Keogh, Simone

    2016-01-01

    SUMMARY Switching from one antidepressant to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. All antidepressant switches must be carried out cautiously and under close observation. Conservative switching strategies involve gradually tapering the first antidepressant followed by an adequate washout period before the new antidepressant is started. This can take a long time and include periods of no treatment with the risk of potentially life-threatening exacerbations of illness. Clinical expertise is needed for more rapid or cross-taper switching as drug toxicity, including serotonin syndrome, may result from inappropriate co-administration of antidepressants. Some antidepressants must not be combined. Antidepressants can cause withdrawal syndromes if discontinued abruptly after prolonged use. Relapse and exacerbation of depression can also occur. Gradual dose reduction over days to weeks reduces the risk and severity of complications. PMID:27346915

  9. Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database

    PubMed Central

    Hill, Trevor; Morriss, Richard; Arthur, Antony; Moore, Michael; Hippisley-Cox, Julia

    2015-01-01

    Objective To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression. Design Cohort study. Setting Patients registered with UK general practices contributing data to the QResearch database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables. Main outcome measures Suicide and attempted suicide or self harm during follow-up. Results During follow-up, 87.7% (n=209 476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79-590 days). During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted

  10. Genetic Prediction of Antidepressant Drug Response and Nonresponse in Korean Patients

    PubMed Central

    Myung, Woojae; Kim, Seonwoo; Kim, Ka-Kyung; Carroll, Bernard J.; Kim, Jong-Won; Kim, Doh Kwan

    2014-01-01

    Genetic polymorphism contributes to variation in response to drug treatment of depression. We conducted three independent 6-week treatment studies in outpatients with major depressive disorder (MDD) to develop a pharmacogenomic model predicting response and nonresponse. We screened candidate genomic markers for association with response to selective serotonin reuptake inhibitors (SSRIs). No patients had received any antidepressant drug treatment in the current episode of depression. Outcome evaluation was blinded to drug and genotype data. The prediction model derived from a development sample of 239 completer cases treated with SSRIs comprised haplotypes and polymorphisms related to serotonin synthesis, serotonin transport, glutamate receptors, and GABA synthesis. The model was evaluated prospectively for prediction of outcome in a validation sample of 176 new SSRI-treated completer cases. The model gave a prediction in 60% of these cases. Predictive values were 85% for predicted responders and 86% for predicted nonresponders, compared to prior probabilities of 66% for observed response and 34% for observed nonresponse in those cases (both P<0.001). Convergent cross-validation was obtained through failure of the model to predict outcomes in a third independent sample of 189 completer cases who received non-SSRI antidepressants. We suggest proof of principle for genetic guidance to use or avoid SSRIs in a majority of Korean depressed patients. PMID:25226239

  11. Genetic prediction of antidepressant drug response and nonresponse in Korean patients.

    PubMed

    Lim, Shinn-Won; Won, Hong-Hee; Kim, Hyeran; Myung, Woojae; Kim, Seonwoo; Kim, Ka-Kyung; Carroll, Bernard J; Kim, Jong-Won; Kim, Doh Kwan

    2014-01-01

    Genetic polymorphism contributes to variation in response to drug treatment of depression. We conducted three independent 6-week treatment studies in outpatients with major depressive disorder (MDD) to develop a pharmacogenomic model predicting response and nonresponse. We screened candidate genomic markers for association with response to selective serotonin reuptake inhibitors (SSRIs). No patients had received any antidepressant drug treatment in the current episode of depression. Outcome evaluation was blinded to drug and genotype data. The prediction model derived from a development sample of 239 completer cases treated with SSRIs comprised haplotypes and polymorphisms related to serotonin synthesis, serotonin transport, glutamate receptors, and GABA synthesis. The model was evaluated prospectively for prediction of outcome in a validation sample of 176 new SSRI-treated completer cases. The model gave a prediction in 60% of these cases. Predictive values were 85% for predicted responders and 86% for predicted nonresponders, compared to prior probabilities of 66% for observed response and 34% for observed nonresponse in those cases (both P<0.001). Convergent cross-validation was obtained through failure of the model to predict outcomes in a third independent sample of 189 completer cases who received non-SSRI antidepressants. We suggest proof of principle for genetic guidance to use or avoid SSRIs in a majority of Korean depressed patients. PMID:25226239

  12. Antidepressant chronotherapeutics for bipolar depression.

    PubMed

    Benedetti, Francesco

    2012-12-01

    Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or "orphan" treatment to a powerful clinical instrument in everyday psychiatric practice. PMID:23393416

  13. Antidepressant chronotherapeutics for bipolar depression

    PubMed Central

    Benedetti, Francesco

    2012-01-01

    Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or “orphan” treatment to a powerful clinical instrument in everyday psychiatric practice. PMID:23393416

  14. Cognitive remediation for vocational rehabilitation nonresponders.

    PubMed

    McGurk, Susan R; Mueser, Kim T; Xie, Haiyi; Feldman, Karin; Shaya, Yaniv; Klein, Leslie; Wolfe, Rosemarie

    2016-08-01

    Cognitive remediation in people with severe mental illnesses (SMI) that interfere with work, but less research has evaluated its effects in those who have not benefitted from vocational services. Participants with SMI (83% schizophrenia) who had not benefitted from vocational rehabilitation were randomized to vocational services enhanced by training vocational specialists in recognizing cognitive difficulties and providing job-relevant cognitive coping strategies (Enhanced Vocational Rehabilitation: E-VR), or similarly enhanced vocational services and cognitive remediation (Thinking Skills Work: TSW). Cognition and symptoms were assessed at baseline, post-treatment (9months), and follow-up (18months), with work tracked weekly for 3years. Fifty-four participants were randomized to E-VR (N=26) or TSW (N=28). Participants in TSW had high rates of exposure to the program (89%) and improved more than those in E-VR on cognitive functioning post-training, with attenuation of some gains at the 18-months. Participants in TSW and E-VR did not differ significantly in competitive work (57% vs. 48%) or paid employment (61% vs. 48%) over the 3-year study, although those in TSW were more likely to be engaged in any work activity, including paid or volunteer work (75% vs. 50%, p=0.057), and had more weeks of work activity (23.04 vs. 48.82, p=0.051), and improved marginally more on the clinical symptoms. The significantly higher education level of participants in E-VR than TSW at baseline may have obscured the effects of TSW. This study supports the feasibility and potential benefits of cognitive remediation for persons who have not benefited from vocational rehabilitation. PMID:27209526

  15. Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington's-like symptoms: a comparative study.

    PubMed

    Kumar, Puneet; Kalonia, Harikesh; Kumar, Anil

    2011-10-01

    Huntington's disease (HD) is characterized by progressive degeneration of neurons in the striatum, cortex and other parts of the brain, causing motor and cognitive dysfunction. 3-Nitropropionic acid (3-NP) is a well-known mycotoxin that significantly induces motor dysfunction in animals. Studies suggested the involvement of oxidative stress and nitric oxide mechanisms in HD pathogenesis. Clinical reports have also indicated the neuroprotective potential of antidepressants. Therefore, the present study has been designed to elucidate and compare the mechanistic role of different antidepressants (sertraline, venlafaxine, imipramine and trazodone) and their interaction with nitric oxide modulators if any, against 3-NP-induced neurotoxicity. Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, motor coordination, oxidative defense and impaired mitochondrial complex enzyme activities in the striatum. Sertraline, venlafaxine, imipramine and trazodone treatments significantly improved behavioral, oxidative defense and mitochondrial complex enzyme activities as compared with the 3-NP-treated group. Systemic L-arginine (50 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly attenuated their protective effect. Similarly, L-nitro-arginine methyl ester (L-NAME) (10 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly potentiated their protective effects which were significant as compared with their effect alone, respectively. The results of the present study suggest that a nitric oxide mechanism might be involved in their protective effect against 3-NP-induced neurotoxicity. PMID:20305041

  16. Influence of Neuropeptide Y and antidepressants upon cerebral monoamines involved in depression: an in vivo electrochemical study.

    PubMed

    Crespi, Francesco

    2011-08-17

    Neuropeptide Y (NPY) and its receptors are present in the peripheral as well as the central nervous system (CNS). In vitro data have indicated NPY as an important mediator in the regulation of different diseases e.g. related to obesity, anxiety, depression, pain, memory loss and sleep disorders. In particular, studies of NPY levels in the cerebral spinal fluid (CSF) of depressed patients have shown a significant reduction of NPY levels when compared to control subjects. In addition, decreased concentrations of NPY were measured in the brain of suicide victims. These studies suggest that a reduction in cerebral NPY function may be associated with depressive symptoms. In the present work, a putative interaction between NPY, the catecholaminergic and serotonergic systems has been analysed by means of in vivo Differential Pulse Voltammetry (DPV) with treated carbon fibre micro electrodes (mCFE). It appeared that DPV with mCFE is an efficacious tool to monitor in vivo basal levels of catechols (Peak 2) and indoles (Peak 3) in discrete brain regions of rodents. Furthermore, it is shown that the peptidergic signal (Peak 5) simultaneously recorded with Peaks 2 and 3 in the amygdala could correspond to the oxidation of basal endogenous NPY. In addition, pharmacological treatments performed in vivo with exogenous NPY and with Y1 receptor antagonist BIBP3226 have indicated that these compounds interact positively with endogenous catecholaminergic and serotoninergic systems, in a way similar to that of the antidepressants imipramine and fluoxetine. In addition, the observed decrease of endogenous Peak 5 after treatment with imipramine or fluoxetine could be related to the concomitant stimulation of the catecholaminergic system with consequent reduced need for endogenous NPY. This would imply that NPY could be one of the endogenous chemicals acting on the maintenance of the mood. Thus, an antidepressant therapeutic potential of NPY and related compounds (e.g. BIBP3226) could be

  17. Utility of event-related potentials in predicting antidepressant treatment response: An iSPOT-D report.

    PubMed

    van Dinteren, Rik; Arns, Martijn; Kenemans, Leon; Jongsma, Marijtje L A; Kessels, Roy P C; Fitzgerald, Paul; Fallahpour, Kamran; Debattista, Charles; Gordon, Evian; Williams, Leanne M

    2015-11-01

    It is essential to improve antidepressant treatment of major depressive disorder (MDD) and one way this could be achieved is by reducing the number of treatment steps by employing biomarkers that can predict treatment outcome. This study investigated differences between MDD patients and healthy controls in the P3 and N1 component from the event-related potential (ERP) generated in a standard two-tone oddball paradigm. Furthermore, the P3 and N1 are investigated as predictors for treatment outcome to three different antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D)--a multi-center, international, randomized, prospective practical trial--1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression. P3 and N1 latencies and amplitudes were analyzed using a peak-picking approach and further replicated by using exact low resolution tomography (eLORETA). A reduced P3 was found in MDD patients compared to controls by a peak-picking analysis. This was validated in a temporal global field power analysis. Source density analysis revealed that the difference in cortical activity originated from the posterior cingulate and parahippocampal gyrus. Male non-responders to venlafaxine-XR had significantly smaller N1 amplitudes than responders. This was demonstrated by both analytical methods. Male non-responders to venlafaxine-XR had less activity originating from the left insular cortex. The observed results are discussed from a neural network viewpoint. PMID:26282359

  18. Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial

    PubMed Central

    Machado-Vieira, Rodrigo; Zarate, Carlos A.; Valiengo, Leandro; Vieira, Erica LM; Benseñor, Isabela M; Lotufo, Paulo A.; Gattaz, Wagner F.; Teixeira, Antonio L

    2014-01-01

    Rationale The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood. Objectives We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial. Methods In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2×2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were determined to investigate the effects of the interventions and of clinical response on them. Results All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders. Conclusions tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode. PMID:24150249

  19. Citalopram, a selective serotonin reuptake inhibitor: clinical antidepressive and long-term effect--a phase II study.

    PubMed

    Pedersen, O L; Kragh-Sørensen, P; Bjerre, M; Overø, K F; Gram, L F

    1982-01-01

    In a phase II study the antidepressive effect of citalopram, a selective and potent serotonin reuptake inhibitor, was examined in 20 endogenously and three non-endogenously depressed hospitalized patients. Four endogenously depressed patients dropped out due to deterioration early in the treatment period. The remaining 19 patients completed a 4-6 week treatment schedule. Of 16 endogenously depressed patients 11 responded, one was a partial responder and four did not respond. Of three patients with non-endogenous depressions, two responded and one did not respond. No correlation between plasma citalopram concentration and therapeutic outcome was found. Fourteen patients were given maintenance treatment for 8-113 weeks. One patient developed depression when the dose was reduced from 60 to 40 mg and one patient became manic. After discontinuation of treatment seven patients had a depressive relapse and six of these who again were treated with citalopram responded completely. Side effect rating scores of symptoms usually associated with depression or treatment with tricyclic antidepressants declined during treatment. Three patients complained of increased need of sleep for a period after several weeks of treatment. Apart from an unspecific, transient rise in liver enzymes in two patients, detailed biochemical laboratory tests were all normal. There were no effects on blood pressure, pulse rate, orthostatic reaction, or electrocardiogram. One patient took an overdose of citalopram resulting in plasma levels about six times higher than the average therapeutic level, but there were no signs of severe toxicity. In particular no change in consciousness, electrocardiogram or blood pressure occurred. Pharmacokinetic variables such as dose schedule, steady state kinetics, and metabolism are discussed. PMID:6812140

  20. RNA expression profiling in depressed patients suggests retinoid-related orphan receptor alpha as a biomarker for antidepressant response.

    PubMed

    Hennings, J M; Uhr, M; Klengel, T; Weber, P; Pütz, B; Touma, C; Czamara, D; Ising, M; Holsboer, F; Lucae, S

    2015-01-01

    Response to antidepressant treatment is highly variable with some patients responding within a few weeks, whereas others have to wait for months until the onset of clinical effects. Gene expression profiling may be a tool to identify markers of antidepressant treatment response and new potential drug targets. In a first step, we selected 12 male, age- and severity-matched pairs of remitters and nonresponders, and analyzed expression profiles in peripheral blood at admission and after 2 and 5 weeks of treatment using Illumina expression arrays. We identified 127 transcripts significantly associated with treatment response with a minimal P-value of 9.41 × 10(-)(4) (false discovery rate-corrected). Analysis of selected transcripts in an independent replication sample of 142 depressed inpatients confirmed that lower expression of retinoid-related orphan receptor alpha (RORa, P=6.23 × 10(-4)), germinal center expressed transcript 2 (GCET2, P=2.08 × 10(-2)) and chitinase 3-like protein 2 (CHI3L2, P=4.45 × 10(-2)) on admission were associated with beneficial treatment response. In addition, leukocyte-specific protein 1 (LSP1) significantly decreased after 5 weeks of treatment in responders (P=2.91 × 10(-2)). Additional genetic, in vivo stress responsitivity data and murine gene expression findings corroborate our finding of RORa as a transcriptional marker of antidepressant response. In summary, using a genome-wide transcriptomics approach and subsequent validation studies, we identified several transcripts including the circadian gene transcript RORa that may serve as biomarkers indicating antidepressant treatment response. PMID:25826113

  1. Factors Associated With Depressive Symptoms and Use of Antidepressant Medications Among Participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies

    PubMed Central

    Fischer, Michael J.; Xie, Dawei; Jordan, Neil; Kop, Willem J.; Krousel-Wood, Marie; Tamura, Manjula Kurella; Kusek, John W.; Ford, Virginia; Rosen, Leigh K.; Strauss, Louise; Teal, Valerie L.; Yaffe, Kristine; Powe, Neil R.; Lash, James P.

    2012-01-01

    Background Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. Study Design Cross-sectional analysis Settings and Participants Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at seven centers from 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois from 2005-2008. Measurement Depressive symptoms measured by Beck Depression Inventory (BDI) Predictors Demographic and clinical factors Outcomes Elevated depressive symptoms (BDI >= 11) and antidepressant medication use Results Among 3853 participants, 28.5% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 30.8% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 25.2% among participants with eGFR ≥ 60 ml/min/1.73m2, and 35.1% of those with eGFR < 30 ml/min/1.73m2. Lower eGFR (OR per 10 ml/min/1.73m2 decrease, 1.09; 95% CI, 1.03-1.16), Hispanic ethnicity (OR, 1.65; 95% CI, 1.12-2.45), and non-Hispanic black race (OR, 1.43; 95% CI, 1.17-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, while female sex was associated with a greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher levels of urine albumin were associated with decreased odds of antidepressant use (p<0.05 for each). Limitations Absence of clinical diagnosis of depression and use of non-pharmacologic treatments Conclusions Although elevated depressive symptoms were common in individuals with CKD, use of

  2. Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: Behavioral and pharmacokinetic studies in mice.

    PubMed

    Poleszak, Ewa; Wlaź, Piotr; Szewczyk, Bernadeta; Kedzierska, Ewa; Wyska, Elzbieta; Librowski, Tadeusz; Szymura-Oleksiak, Joanna; Fidecka, Sylwia; Pilc, Andrzej; Nowak, Gabriel

    2005-07-01

    The effect of joint administration of imipramine (IMI) and magnesium (Mg) on antidepressant-like activity was studied in mice using forced swim test (FST). Mg doses ineffective per se (5 and 10 mg/kg) given jointly with IMI also at ineffective doses (10 and 15 mg/kg) resulted in a potent reduction in the immobility time. Since these combined treatments did not influence locomotor activity, the antidepressant-like activity was not due to non-specific behavioral activation. Moreover, we estimated the effect of joint administration of magnesium and IMI in FST on serum and brain magnesium, IMI and its active metabolite desipramine (DMI) concentrations in mice. Swim stress (mice subjected to FST) increased the magnesium concentration in serum and decreased it in the brain compared to naive animals. Moreover administration of IMI increased (normalized) magnesium brain concentration, without influence on the serum level. Joint administration of IMI and magnesium did not influence magnesium (compared with FST) or IMI and DMI (compared with IMI treatment alone) concentrations in both examined tissues. The present data demonstrated an enhancement of the antidepressant-like effect by joint administration of IMI and magnesium in the FST, and further indicate the particular role of magnesium in the antidepressant action. Since there was no increase in IMI, DMI or magnesium concentration after joint administration of magnesium and IMI, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between magnesium and IMI is accountable for behavioral effect in the FST. PMID:15936065

  3. A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response.

    PubMed

    Posternak, Michael; Novak, Scott; Stern, Robert; Hennessey, James; Joffe, Russell; Prange, Arthur; Zimmerman, Mark

    2008-02-01

    The aim was to evaluate whether adjunctive T3 can help accelerate the antidepressant response and improve overall outcomes when used under naturalistic conditions. Fifty consecutive psychiatric outpatients diagnosed with major depressive disorder who were initiated on antidepressant therapy were randomized to receive adjunctive T3 or placebo in a double-blind manner over the course of 6 wk. There were no restrictions placed on the selection of antidepressant agent, dosing, ancillary medications, or psychotherapy, and there were few exclusion criteria. A positive response was defined as a > or = 50% reduction in Montgomery-Asberg Depression Rating Scale scores. Response rates were higher for the adjunctive T3 cohort compared to the adjunctive placebo cohort after 1 wk (45% vs. 24%) and 2 wk (57% vs. 33%) of treatment. The likelihood of experiencing a positive response at any point over the 6-wk trial was 4.5 times greater in the adjunctive T3 cohort (95% CI 1.3-15.7). The study provides preliminary evidence that T3 can successfully be used in clinical practice to accelerate the antidepressant response and improve overall outcomes. The effectiveness model may be an untapped mechanism for evaluating the value of psychopharmacological agents. PMID:17352847

  4. Prevalence and Prescription of Antidepressants in Depression with Somatic Comorbidity in Asia: The Research on East Asian Psychotropic Prescription Patterns Study

    PubMed Central

    Chen, Chao; Si, Tian-Mei; Xiang, Yu-Tao; Ungvari, Gabor S; Wang, Chuan-Yue; He, Yan-Ling; Kua, Ee-Heok; Fujii, Senta; Sim, Kang; Trivedi, Jitendra K; Chung, Eun-Kee; Udomratn, Pichet; Chee, Kok-Yoon; Sartorius, Norman; Tan, Chay-Hoon; Shinfuku, Naotaka

    2015-01-01

    Background: Depression is often comorbid with chronic somatic diseases. Few previous studies have investigated the prevalence of somatic diseases in depression or the prescription pattern of antidepressants in comorbidly depressed patients in Asia. This study aimed to investigate the prevalence of somatic comorbidity (SC) in depression and compared the prescriptions of antidepressants in depressed patients with and without SC. Methods: A total of 2320 patients treated with antidepressants in 8 Asian countries were examined, and a diagnosis was based on the International Classification of Disease, 10th revision. We listed 17 common chronic somatic diseases. Patients’ socio-demographic and clinical characteristics and psychotropic drug prescriptions were recorded using a standardized protocol and data collection procedure. Results: Of the patients examined, 1240 were diagnosed with depression and 30% of them (n = 375) had SC. The most common comorbid condition was diabetes (23.7%). The patients with SC were more likely to seek help at a general hospital (74.7% vs. 47.2%), and had a higher incidence of symptoms involving sadness, disturbed sleep, and poor appetite. Noradrenergic and specific serotonergic antidepressant was prescribed more for patients with SC than for those without SC (30.4% vs. 22.9%). Conclusions: SC is common in depressed Asian patients. It is important to strengthen the recognition of depression, especially in general hospitals and when patients report some somatic discomfort. It is also a matter of urgency to establish evidence-based guidelines for the use of new antidepressants in depressed patients with SC. PMID:25836602

  5. Placental transfer of antidepressant medications: implications for postnatal adaptation syndrome.

    PubMed

    Ewing, Grace; Tatarchuk, Yekaterina; Appleby, Dina; Schwartz, Nadav; Kim, Deborah

    2015-04-01

    Seven to thirteen percent of women are either prescribed or taking (depending on the study) an antidepressant during pregnancy. Because antidepressants freely cross into the intrauterine environment, we aim to summarize the current findings on placental transfer of antidepressants. Although generally low risk, antidepressants have been associated with postnatal adaptation syndrome (PNAS). Specifically, we explore whether the antidepressants most closely associated with PNAS (paroxetine, fluoxetine, venlafaxine) cross the placenta to a greater extent than other antidepressants. We review research on antidepressants in the context of placental anatomy, placental transport mechanisms, placental metabolism, pharmacokinetics, as well as non-placental maternal and fetal factors. This provides insight into the complexity involved in understanding how placental transfer of antidepressants may relate to adverse perinatal outcomes. Ultimately, from this data there is no pattern in which PNAS is related to placental transfer of antidepressant medications. In general, there is large interindividual variability for each type of antidepressant. To make the most clinically informed decisions about the use of antidepressants in pregnancy, studies that link maternal, placental and fetal genetic polymorphisms, placental transfer rates and infant outcomes are needed. PMID:25711391

  6. Pharmacogenetics of antidepressant response

    PubMed Central

    Porcelli, Stefano; Drago, Antonio; Fabbri, Chiara; Gibiino, Sara; Calati, Raffaella; Serretti, Alessandro

    2011-01-01

    Personalized medicine — the adaptation of therapies based on an individual’s genetic and molecular profile — is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmacodynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs. PMID:21172166

  7. Influence of antidepressants on hemostasis.

    PubMed

    Halperin, Demian; Reber, Guido

    2007-01-01

    Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition--fluoxetine, paroxetine, and sertraline--are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge. PMID

  8. Oxidation of tricyclic antidepressant drugs with chloramine-T in acidic solutions: kinetic, mechanistic and thermodynamic studies.

    PubMed

    Sukhdev, Anu; Puttaswamy, Puttaswamy

    2013-12-01

    The kinetics of the oxidation of two tricyclic antidepressants (TCA) namely, imipramine (IMP) and clomipramine (CLM) with sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in HClO4 medium was studied at 300 K. The two reactions followed identical kinetics with a first-order dependence of rate on [CAT]o and fractional order dependence on [TCA]o. The reaction is catalyzed by H(+) ions with a fractional order dependence. The reaction was studied at different temperatures and activation parameters were evaluated. The reaction constants involved in the mechanism were computed. The solvent isotope effect was studied using D2O. Addition of p-toluenesulfonamide retards the reaction rate. The rate increased with decreasing dielectric constant of the medium. Variation of ionic strength of the medium and addition of halide ions (Cl(-) or Br(-)) showed no effect on the rate. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as imipramine-5-N-oxide and clomipramine-5-N-oxide. The rate of oxidation of IMP is faster than CLM. The observed results have been explained in terms of a mechanism and a relevant rate law has been deduced. PMID:23543721

  9. Docking studies of antidepressants against single crystal structure of tryptophan 2, 3-dioxygenase using Molegro Virtual Docker software.

    PubMed

    Dawood, Shazia; Zarina, Shamshad; Bano, Samina

    2014-09-01

    Tryptophan 2, 3-dioxygenase (TDO) a heme containing enzyme found in mammalian liver is responsible for tryptophan (Trp) catabolism. Trp is an essential amino acid that is degraded in to N-formylkynurenine by the action of TDO. The protein ligand interaction plays a significant role in structural based drug designing. The current study illustrates the binding of established antidepressants (ADs) against TDO enzyme using in-silico docking studies. For this purpose, Fluoxetine, Paroxetine, Sertraline, Fluvoxamine, Seproxetine, Citalopram, Moclobamide, Hyperforin and Amoxepine were selected. In-silico docking studies were carried out using Molegro Virtual Docker (MVD) software. Docking results show that all ADs fit well in the active site of TDO moreover Hyperforin and Paroxetine exhibited high docking scores of -152.484k cal/mol and -139.706k cal/mol, respectively. It is concluded that Hyperforin and Paroxetine are possible lead molecules because of their high docking scores as compared to other ADs examined. Therefore, these two ADs stand as potent inhibitors of TDO enzyme. PMID:25176248

  10. Effectiveness of Duloxetine Monotherapy Compared to Combination Therapy with Other Antidepressants in Patients with Major Depressive Disorder: A Short-Term, Retrospective Study

    PubMed Central

    Cheon, Eun-Jin; Lee, Jun-Yeob; Choi, Joong-Hyeon; Lee, Young-Ji

    2016-01-01

    Objective The purpose of this study was to compare duloxetine monotherapy to combination therapy with other antidepressants in patients with major depressive disorder in a clinical, real world setting. Methods An eight-week, retrospective, multi-center study of outpatients with major depressive disorder was undertaken. After screening 415 patients, enrolled in this study from July 2009 to June 2014 were 82 patients from among three centers who had been taking duloxetine with or without other antidepressant and not administered with atypical antipsychotics. We compared the mean changes of the Clinical Global Impression-Severity Scale (CGI-S) as a primary measure and the discontinuation rate as a secondary measure between the duloxetine monotherapy group (n=36, 43.9%) and the combination therapy with other antidepressants group (n=46, 56.1%) at baseline, one, two, four and eight weeks. Results There were no significant differences across the demographic characteristics between two groups. There was, however, a statistically greater improvement on the CGI-S at weeks 2, 4 and 8 in the combination group compared with the monotherapy group. There were no significant differences in discontinuation rate and adverse events between two groups. No serious adverse events were reported in both groups during the study period. Conclusion This result suggests that the duloxetine combination therapy with other antidepressants could improve effectiveness and have comparable tolerability with the monotherapy in the treatment of outpatients with major depressive disorders in a naturalistic setting. Adequately powered, well-controlled clinical trials are strongly warranted to confirm our findings due to methodological shortcomings. PMID:27482247

  11. New Framework To Diagnose the Direct Disposal of Prescribed Drugs in Wastewater - A Case Study of the Antidepressant Fluoxetine.

    PubMed

    Petrie, Bruce; Youdan, Jane; Barden, Ruth; Kasprzyk-Hordern, Barbara

    2016-04-01

    Intentional or accidental release (direct disposal) of high loads of unused pharmaceuticals into wastewater can go unnoticed. Here, direct disposal of a pharmaceutical drug via the sewer network was identified for the first time using wastewater analysis. An irregularly high load of the antidepressant fluoxetine in raw wastewater (10.5 ± 2.4 g d(-1)) was up to 11 times greater than any other day. National prescription data revealed a predicted daily fluoxetine load for the studied treatment works to be 0.4-1.6 g d(-1). Enantio-selective analysis showed the high load of fluoxetine was present as a racemic mixture, which is typical for fluoxetine in dispensed formulations. As fluoxetine undergoes stereoselective metabolism within the body, a racemic mixture in wastewater suggests a nonconsumed drug was the major contributor of the high load. This was confirmed by its major metabolite norfluoxetine whose load did not increase on this day. Considering the most commonly prescribed formulation of fluoxetine, this increased load accounts for the disposal of ∼915 capsules. Furthermore, as fluoxetine is prescribed as one capsule per day, disposal is unlikely to be at the patient level. It is postulated that direct disposal was from a facility which handles larger quantities of the drug (e.g., a pharmacy). PMID:26974167

  12. Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study

    PubMed Central

    Gupta, Gaurav; Jia Jia, Tay; Yee Woon, Lim; Kumar Chellappan, Dinesh; Candasamy, Mayuren; Dua, Kamal

    2015-01-01

    The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n = 6) for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p > 0.05). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group (p < 0.001) and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg). PMID:26681936

  13. Combination treatment of fingolimod with antidepressants in relapsing–remitting multiple sclerosis patients with depression: a multicentre, open-label study – REGAIN

    PubMed Central

    Bayas, Antonios; Schuh, Katrin; Baier, Monika; Vormfelde, Stefan Viktor; Koppai-Reiner, Joachim

    2016-01-01

    Objectives: Approximately one in two patients with multiple sclerosis (MS) suffer from comorbid depression. The primary objective of this study was to evaluate the safety and tolerability of fingolimod and antidepressant combination in relapsing–remitting MS patients with mild-to-moderate depression. Efficacy outcome variables were quality of life (QoL), fatigue, disability and depression. Methods: Patients received open-label fingolimod 0.5 mg over 2 weeks, followed by fingolimod plus citalopram (40 mg), fluoxetine (40 mg) or venlafaxine (150 mg) over 16 weeks. The antidepressant was selected at the physician’s discretion. Results: In total, 54 patients were recruited at 25 centres across Germany. No new safety signals (including cardiac) emerged compared with previous clinical studies. Adverse events (mostly mild-to-moderate) were reported in 43 patients. A total of three patients had serious adverse events and 10 discontinued the study. QoL (mean [95% confidence interval]) improved by 2.2 (−3.3, −1.2; Patient Reported Indices for MS questionnaire), fatigue by 8.2 (−13.1, −3.3; modified Fatigue Impact Scale) and depression by 6.3 (−8.4, −4.2; Hamilton Depression Scale) points. However, the results must be interpreted cautiously owing to limited patient numbers. Conclusions: Combination of fingolimod with antidepressant medication showed no unexpected safety signals. Patient-reported outcomes (QoL, disability, fatigue and depression) remained stable or improved. PMID:27582893

  14. Chemistry, Pharmacology, and Behavioral Studies Identify Chiral Cyclopropanes as Selective α4β2- Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile. Part II

    PubMed Central

    Zhang, Han-Kun; Yu, Li-Fang; Eaton, J. Brek; Whiteaker, Paul; Onajole, Oluseye K.; Hanania, Taleen; Brunner, Daniela; Lukas, Ronald J.; Kozikowski, Alan P.

    2013-01-01

    A 3-pyridyl ether scaffold bearing a cyclopropane-containing side chain was recently identified in our efforts to create novel antidepressants that act as partial agonists at α4β2-nicotinic acetylcholine receptors. In this study, a systematic structure-activity relationship investigation was carried out on both the azetidine moiety present in compound 3 and its right-hand side chain, thereby discovering a variety of novel nicotinic ligands that retain bioactivity and feature improved chemical stability. The most promising compounds 24, 26, and 30 demonstrated comparable or enhanced pharmacological profiles compared to the parent compound 4, and the N-methylpyrrolidine analogue 26 also exhibited robust antidepressant-like efficacy in the mouse forced swim test. The favorable ADMET profile and chemical stability of 26 further indicate this compound to be a promising lead as a drug candidate warranting further advancement down the drug discovery pipeline. PMID:23734673

  15. Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants.

    PubMed

    Browne, Caroline A; Lucki, Irwin

    2013-01-01

    Newer antidepressants are needed for the many individuals with major depressive disorder (MDD) that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine's effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse potential of ketamine

  16. An experimental antidepressant increases REM sleep.

    PubMed

    Soldatos, C R; Stefanis, C N; Bergiannaki, J D; Christodoulou, C; Botsis, A; Sakkas, P N

    1988-01-01

    1. An experimental antidepressant was studied through sleep laboratory recordings, psychoendocrinological tests and clinical measurements in terms of its efficacy, side effects and effects on sleep. 2. The design included a four-week drug administration period, preceeded and followed by a one week placebo period. 3. In the presence of antidepressant efficacy, the drug did not disturb sleep induction and maintainance. 4. The only effect on sleep stages was an increase of REM sleep during the short-term drug administration period which is contrary to the REM supressant effect of most antidepressants. 5. This finding suggests that REM supression and antidepressant efficacy are not necessarily related. 6. Further, given that the only known action of the drug is its inhibitory effect on GABAergic transmission, one can speculate that GABA mechanisms may be involved in REM sleep modulation. PMID:3241873

  17. [Are antidepressants really effective?].

    PubMed

    Ammendola, S; Kornreich, C

    2015-01-01

    Antidepressants are widely used for a long time and it is estimated that about 10 % of the belgian population is taking some of them each year. However, there are important controversies about their real efficacy. We review successively arguments for and against their efficacy. On the one hand, meta-analysis have shown no big efficacy differences between antidepressants and placebo. On the other hand, those meta-analysis have been criticized for their methodology. Animal models show a real effect of antidepressants on the brain and clinical observations, such as an impact on suicide prevention, the possibility of induced manic switch, and an efficacy on anxiety disorders are in favour of a real efficacy. Given our current state of knowledge about them it seems appropriate to continue to use anti-depressants in the treatment of depressive patients. PMID:26749632

  18. MedlinePlus: Antidepressants

    MedlinePlus

    ... and Learn No links available Research Statistics and Research Clinical Trials Journal Articles Resources Find an Expert For You Children Women Patient Handouts Summary Antidepressants are medicines that treat ...

  19. Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance.

    PubMed

    Walker, Adam J; Foley, Brittany M; Sutor, Shari L; McGillivray, Jane A; Frye, Mark A; Tye, Susannah J

    2015-10-15

    Ketamine, N-methyl-d-aspartate (NMDA) receptor antagonist and anti-inflammatory agent, has rapid therapeutic effects in a subset of patients with more intractable forms of depression. Irregular proinflammatory cytokine and acute-reactive protein levels have been reported in clinical and preclinical depression research. We explored the association between the rapid antidepressant-like effects of ketamine and peripheral proinflammatory profile in a model of antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24) 100μg/d or saline (0.9%) for 14d. Antidepressant-like effects were assessed with the forced swim test (FST). Ketamine (10mg/kg) significantly reduced immobility duration in saline-pretreated control animals. In contrast, a divergent response was observed in ACTH-pretreated antidepressant resistant animals, with 50% responders and 50% non-responders. Plasma samples were analyzed via enzyme-linked immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Levels of CRP and TNFα differentiated ketamine responders and non-responders. PMID:26209292

  20. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study

    PubMed Central

    Reiss, Peter; Shetty, Hitesh; Broadbent, Matthew; Stewart, Robert; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Objectives To investigate the association between antidepressant therapy and the later onset of mania/bipolar disorder. Design Retrospective cohort study using an anonymised electronic health record case register. Setting South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. Participants 21 012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression. Exposure Prior antidepressant therapy recorded in electronic health records. Main outcome measure Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014. Methods Multivariable Cox regression analysis with age and gender as covariates. Results The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70). Conclusions In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression. PMID:26667012

  1. The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine – Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model

    PubMed Central

    Ding, Lingling; Zhang, Xiaoyu; Guo, Hongliang; Yuan, Junliang; Li, Shujuan; Hu, Wenli; Golden, Teresa; Wu, Ning

    2015-01-01

    Jie Yu Chu Fan capsule (JYCF) is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS) mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC). The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg) and fluoxetine (20mg/kg) significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg) significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively) and 5-HT in hippocampus (P < 0.05). In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE. PMID:26186537

  2. A Canadian Primary Care Sentinel Surveillance Network Study Evaluating Antidepressant Prescribing in Canada From 2006 to 2012

    PubMed Central

    Morkem, Rachael; Barber, David; Williamson, Tyler; Patten, Scott B

    2015-01-01

    Objective: To evaluate the prescribing patterns of antidepressants (ADs) by primary care providers to youth, adults, and seniors, from 2006 to 2012, using data from electronic medical records (EMRs). Method: This was a retrospective cross-sectional database study that used primary care data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Data on more than 600 000 Canadian primary care patients were used to determine the prevalence and incidence of AD prescribing to patients 15 years and older who had an encounter in the years of study (from 2006 to 2012). Each study year was evaluated independently. Results: The study population consisted of 86 927 patients in 2006 (mean age 48.1 years [SD 18.7], 38% male) and grew to 273 529 (mean age 49.6 years [SD 19.3], 40% male) in 2012. The prevalence of AD prescribing increased from 9.20% in 2006 to 12.80% in 2012 (P < 0.001). While the incidence rate of AD prescribing dropped from 3.54% in 2006 to 2.72% in 2008 (P < 0.001) the rate started to significantly rise again, reaching an incidence of 3.07% by 2012 (P < 0.001). Conclusions: The prevalence of AD prescribing by primary care providers in Canada continued to rise from 2006 to 2012. Conversely, incidence has remained stable or declined during the 6-year study period. While many complex factors likely contribute to the observed prevalence and incidence rates, our findings suggest that the guidelines indicating the efficacy of long-term AD therapy for patients with highly recurrent or severe depression are being followed. PMID:26720825

  3. Antidepressants and Driving in Older Adults: A Systematic Review.

    PubMed

    Cameron, Duncan H; Rapoport, Mark J

    2016-06-01

    With an increasing number of older drivers who are prescribed antidepressants, the potential consequences of antidepressant use on driving skills in an aging population are becoming a pressing issue. We conducted a systematic review using MEDLINE, targeting articles specifically pertaining to antidepressants and driving in a population or subgroup of older adults (≥ 55 years of age). The search yielded 267 references, nine of which pertained to the effects of antidepressants on driving in older adults. The single experimental study found imipramine to have detrimental effects on highway driving, whereas nefazodone did not. Seven of eight population-based studies reported a significant increased risk of involvement in a collision associated with antidepressant use. Although the studies indicated a negative effect of antidepressants on driving, the epidemiological designs cannot exclude the possibility that the underlying illness, generally major depression, is the culprit. PMID:27091414

  4. Treatment Satisfaction Among Patients Taking Antidepressant Medication.

    PubMed

    López-Torres Hidalgo, Jesús; López Gallardo, Yolanda; Párraga Martínez, Ignacio; Del Campo Del Campo, José María; Villena Ferrer, Alejandro; Morena Rayo, Susana

    2016-08-01

    This study sought to assess treatment satisfaction among patients on antidepressants, ascertaining whether there might be an association with depressive symptomatology and other variables. Cross-sectional study conducted on 564 adult patients taking antidepressant medication. Satisfaction with antidepressant treatment was assessed using the Assessment of Satisfaction with Antidepressant Treatment Questionnaire (ESTA/Evaluación de la Satisfacción con el Tratamiento Antidepresivo). A moderate negative correlation was observed between satisfaction and intensity of depressive symptoms, as assessed with the Montgomery-Asberg scale. A weak negative correlation was observed between greater satisfaction and less favourable views about taking medication. Satisfaction scale scores were higher among those who took antidepressant medication for 1 year or more versus shorter periods. Most patients reported being satisfied with the antidepressant treatment but the level of satisfaction was higher among those who presented with less marked depressive symptoms, received longer-term treatment and viewed drug treatments favourably. Treatment satisfaction is one of the patient-reported outcome measures that can serve to complement clinical evaluation of depressive disorders. PMID:25833726

  5. Associations Between Personality Traits and Adherence to Antidepressants Assessed Through Self-Report, Electronic Monitoring, and Pharmacy Dispensing Data: A Pilot Study.

    PubMed

    Wouters, Hans; Amin, Darya F H; Taxis, Katja; Heerdink, Eibert R; Egberts, Antoine C G; Gardarsdottir, Helga

    2016-10-01

    Treatment with antidepressants is often compromised by substantial nonadherence. To understand nonadherence, specific medication-related behaviors and beliefs have been studied, but less is known about broader and temporally stable personality "traits." Furthermore, adherence has often been assessed by a single method. Hence, we investigated associations between the Big Five personality traits and adherence assessed by self-report, electronic drug use monitoring, and dispensing data. Using the Big Five Inventory, we assessed the personality traits "openness," "conscientiousness," "extraversion," "agreeableness," and "neuroticism" of patients treated with antidepressants who were invited through community pharmacies. Self-reported adherence was assessed with the Medication Adherence Rating Scale (score >24), electronic monitoring with medication event monitoring system (MEMS) devices (therapy days missed ≤ 10% and < 4 consecutive days missed), and dispensing data (medication possession ratio ≥ 80%). One hundred four women and 33 men participated (mean age, 51; standard deviation, 14). Paroxetine was most frequently prescribed (N = 53, 38%). Logistic regression analysis revealed that of the personality traits, the third and fourth quartiles of "conscientiousness" were associated with better self-reported adherence (odds ratio, 3.63; 95% confidence interval, 1.34-9.86 and odds ratio, 2.97; 95% confidence interval, 1.09-8.08; P ≤ 0.05). No relationships were found between personality traits and adherence assessed through electronic drug use monitoring or dispensing data. We therefore conclude that adherence to antidepressant therapy seems to be largely unrelated to personality traits. PMID:27454894

  6. Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression.

    PubMed

    Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

    2016-01-01

    Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors-overall trauma 'load' and specific type of abuse-on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer outcomes

  7. Folate augmentation of antidepressant response.

    PubMed

    Owen, R T

    2013-12-01

    The use of two antidepressants from the initiation of treatment in major depressive disorder has been investigated in several recent studies and forms a paradigm shift in the pharmacotherapy of the condition. Several, but not all, trials have claimed improved response and remission rates with the combinations as opposed to monotherapy. The use of folate preparations (folic and folinic acid and l-meth-ylfolate) have shown effective augmentation of antidepressant response in a variety of controlled and open-label settings in patients with normo- and hypofolatemic status. Several recent trials using L-methylfolate, the active and more bioavailable form of folic acid, have shown promising adjunctive use with a well-tolerated adverse event profile. PMID:24524097

  8. Use of SSRI and SNRI Antidepressants during Pregnancy: A Population-Based Study from Denmark, Iceland, Norway and Sweden

    PubMed Central

    Zoega, Helga; Kieler, Helle; Nørgaard, Mette; Furu, Kari; Valdimarsdottir, Unnur; Brandt, Lena; Haglund, Bengt

    2015-01-01

    Background The purpose was to describe utilization of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), including trends in prevalence, characteristics of users, drug switching and changes in prescribed doses in a large group of pregnant women across four Nordic countries. Methods A drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics. Results A total of 38 219 (3.3%) pregnancies were exposed to SSRIs and 5 634 (0.5%) to SNRIs. Prevalence of SSRI and SNRI use varied by country (1.8% in Norway to 7.0% in Iceland). Use and prescribed dosages decreased with each passing trimester of pregnancy; prevalence was 2.7% at conception, and 2.1%, 1.7% and 1.3% respectively in 1st, 2nd and 3rd trimester. In 0.6% of pregnancies women filled a prescription before pregnancy and in every trimester. In one third of exposed pregnancies, women were also dispensed anxiolytics, hypnotics or sedatives. Conclusion Use of SSRI and SNRI use during pregnancy varied between the Nordic countries, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women. PMID:26657647

  9. The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study

    PubMed Central

    Wang, Sheng-Min; Kim, Jung-Bum; Sakong, Jeong Kyu; Suh, Ho-Suk; Oh, Kang Seob; Woo, Jong-Min; Yoo, Sang-Woo; Lee, Sang Min; Lee, Sang-Yeol; Lim, Se-Won; Cho, Seong Jin; Chee, Ik-Seung; Chae, Jeong-Ho; Hong, Jin Pyo; Lee, Kyoung-Uk

    2016-01-01

    Objective This study compared the efficacy and tolerability of clonazepam with other benzodiazepines in patients with anxiety disorders. Methods Inclusion criteria were as follows: age >20 years, diagnosis of anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) criteria, taking only one type of antidepressant, and prescribed one of three oral benzodiazepines (alprazolam, clonazepam, or lorazepam). At baseline and week 6, clinical benefit was evaluated using the Clinical Global Impression-Severity Scale (CGI-S), Clinical Global Impression-Anxiety Scale (CGI-anxiety), and Clinical Global Impression-Sleep Scale (CGI-sleep). Results Among 180 patients, no differences in demographic characteristics among the three benzodiazepine groups were noted. After six weeks of treatment, all benzodiazepine groups showed significant improvements in CGI-S, CGI-anxiety, and CGI-sleep scores (p<0.001). There were no differences in mean changes in CGI-S, CGI-anxiety and CGI-sleep among the three benzodiazepine groups. The incidence of side effects was significantly lower in the clonazepam group than with the other benzodiazepines. The incidences of adverse events for the clonazepam, alprazolam, and lorazepam groups were 26.7% (n=20), 48.4% (n=31), and 43.9% (n=18), respectively. Conclusion The present study suggests that clonazepam is as efficacious as other benzodiazepines for the treatment of various anxiety disorders. Furthermore, the safety profile of clonazepam was superior to the other benzodiazepines in this study. PMID:27121429

  10. Diabetes mellitus and comorbid depression: improvement of both diseases with milnacipran. A replication study (results of the Austrian Major Depression Diabetes Mellitus study group).

    PubMed

    Abrahamian, Heidemarie; Hofmann, Peter; Kinzl, Johann; Toplak, Hermann

    2012-01-01

    Comorbid depression is common in patients with type 2 diabetes mellitus and is associated with greater mortality risk and a higher incidence of diabetic complications and decreased quality of life. In an earlier pilot study, we found that treatment with the serotonin norepinephrine reuptake inhibitor antidepressant, milnacipran, significantly improved metabolic parameters in diabetic patients with comorbid depression who had an antidepressant response. We sought to replicate these results in a larger cohort (n = 135). Patients received milnacipran and metformin for 6 months and metabolic parameters and depressive symptoms were measured at baseline and after 3 and 6 months. At the end of the study, 72.6% of patients had an antidepressant response (≥50% reduction of baseline Beck Depression Inventory score). Overall, there was significant improvement in the metabolic and anthropometric parameters measured. The number of patients with glycated hemoglobin > 8% (>63.9 mmol/mol), an indicator of poor metabolic control requiring intensive therapeutic intervention, decreased from 31.9% at baseline to 11.9% during the study. As found in the pilot study, levels of total cholesterol and triglycerides were only significantly decreased in antidepressant responders. Body weight was significantly reduced in both responders and nonresponders but the effect size was significantly greater in the responder group. In contrast to the pilot study, fasting blood glucose and glycated hemoglobin were significantly decreased to a similar extent in both antidepressant-responders and nonresponders. The present study thus replicates some of the original findings. The main difference between the present and the pilot study is that in the larger cohort significant reductions in fasting blood glucose and glycated hemoglobin were found in all patients irrespective of whether or not they responded to antidepressant treatment. The present data underline the importance of diagnosis and treatment of

  11. CNS- and ANS-arousal predict response to antidepressant medication: Findings from the randomized iSPOT-D study.

    PubMed

    Olbrich, Sebastian; Tränkner, Anja; Surova, Galina; Gevirtz, Richard; Gordon, Evian; Hegerl, Ulrich; Arns, Martijn

    2016-02-01

    Arousal systems are one of the recently announced NIMH Research Domain Criteria to inform future diagnostics and treatment prediction. In major depressive disorder (MDD), altered central nervous system (CNS) wakefulness regulation and an increased sympathetic autonomic nervous system (ANS) activity have been identified as biomarkers with possible discriminative value for prediction of antidepressant treatment response. Therefore, the hypothesis of a more pronounced decline of CNS and ANS-arousal being predictive for a positive treatment outcome to selective-serotonin-reuptake-inhibitor (SSRI) treatment was derived from a small, independent exploratory dataset (N = 25) and replicated using data from the randomized international Study to Predict Optimized Treatment Response in Depression (iSPOT-D). There, 1008 MDD participants were randomized to either a SSRI (escitalopram or sertraline) or a serotonin-norepinephrine-reuptake-inhibitor (SNRI-venlafaxine) arm. Treatment response was established after eight weeks using the 17-item Hamilton Rating Scale for Depression. CNS-arousal (i.e. electroencephalogram-vigilance), ANS-arousal (heart rate) and their change across time were assessed during rest. Responders and remitters to SSRI treatment were characterized by a faster decline of CNS-arousal during rest whereas SNRI responders showed a significant increase of ANS-arousal. Furthermore, SSRI responders/remitters showed an association between ANS- and CNS-arousal regulation in comparison to non-responders/non-remitters while this was not the case for SNRI treatment arm. Since positive treatment outcome to SSRI and SNRI was linked to distinct CNS and ANS-arousal profiles, these predictive markers probably are not disorder specific alterations but reflect the responsiveness of the nervous system to specific drugs. PMID:26714202

  12. Mirtazapine: a newer antidepressant.

    PubMed

    Hartmann, P M

    1999-01-01

    Mirtazapine is a newer antidepressant that exhibits both noradrenergic and serotonergic activity. It is at least as effective as the older antidepressants for treating mild to severe depression. Sedation is the most common side effect. Although agranulocytosis is the most serious side effect, it is rare (approximately one in 1,000) and usually reversible when the medication is stopped. Mirtazapine is relatively safe in overdose. Many clinicians consider mirtazapine a second-line or even third-line antidepressant to be used when older antidepressants are not tolerated or are ineffective. Physicians who are concerned about the risks of elevated lipid levels and agranulocytosis may choose to reserve mirtazapine as a third-line choice. It is particularly useful in patients who experience sexual side effects from other antidepressants. Mirtazapine is also a good choice in depressed patients with significant anxiety or insomnia. Although mirtazapine has been used successfully in Europe for a number of years, its place in the care of patients with depression in the United States has not yet been established. PMID:9917581

  13. Antipsychotics as antidepressants.

    PubMed

    Roberts, Rona Jeannie; Lohano, Kavita K; El-Mallakh, Rif S

    2016-09-01

    Three second-generation antipsychotic (SGA) agents have received FDA approval for adjunctive treatment, to antidepressant, of major depressive disorder: quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone have been approved for the treatment of bipolar depression. There are data suggesting that quetiapine is effective for major depressive disorder as monotherapy. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all SGA will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e., produce a depression-like clinical picture). The antidepressant effect appears to be unique to some agents, with direct evidence of insignificant antidepressant action for ziprasidone. Three general principles can guide the use of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects; (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic doses are to be used; and (iii) SGAs do not have a general antidepressant effect, rather, this appears to be unique to quetiapine and aripiprazole, and possibly lurasidone. PMID:25963405

  14. Generic prescribing of antidepressants.

    PubMed

    Bruck, P; Antao, C A; Henry, J A

    1992-11-01

    Analysis of National Health Service prescription data for the antidepressants from 1980 to 1989 shows a consistent secular trend towards the increased use of generic names on prescriptions for this group of drugs. This apparently reflects national trends for all drugs, and was similar for most antidepressants. However, generic prescribing had by 1989 increased significantly more rapidly with fluvoxamine, which was introduced in 1987. The two drugs introduced in 1989, fluoxetine and amoxapine, also had a high generic prescribing rate in their year of introduction. Increased generic prescribing may become a feature with further new drugs. However, the use of the generic name on the prescription has relatively little influence on what is dispensed to the patient. Pharmacists may dispense a brand name when given a generic prescription. Moreover, pressures on doctors to write generic names on prescriptions may have limited relevance for some drugs; generic alternatives were available for only four out of 22 antidepressants. PMID:1474553

  15. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

    PubMed Central

    Guski, Louise Schow; Freund, Nanna; Gøtzsche, Peter C

    2016-01-01

    Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors. Design Systematic review and meta-analysis. Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website. Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model). Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was

  16. Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.

    PubMed

    Neis, Vivian Binder; Moretti, Morgana; Manosso, Luana Meller; Lopes, Mark W; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

    2015-03-01

    Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. PMID:25553821

  17. Clinical Utility of Combinatorial Pharmacogenomics-Guided Antidepressant Therapy: Evidence from Three Clinical Studies.

    PubMed

    Altar, C Anthony; Carhart, Joseph; Allen, Josiah D; Hall-Flavin, Daniel; Winner, Joel; Dechairo, Bryan

    2015-10-01

    DNA of 258 patients with treatment-resistant depression was collected in three 8-10 week, two-arm, prospective clinical trials. Forty-four allelic variations were measured in genes for the cytochrome P450 (CYP) enzymes CYP2D6, CYPC19, and CYP1A2, the serotonin transporter (SLC6A4), and the 5-HT2A receptor (HTR2A). The combinatorial pharmacogenomic (CPGx™) GeneSight test results were provided to clinicians to support medication changes from baseline (guided arm), or they were provided at the end of each study to clinicians of unguided patients who were treated as usual (TAU). TAU subjects who at baseline were prescribed medications genetically discordant for them showed only a 12% symptom improvement, far less than the 32.5% or 28.5% improvements of the TAU subjects on yellow-category ('use with caution'; p = 0.002) or green-category medications ('use as recommended'; p = 0.02), respectively. The odds of a clinical response were increased 2.3-fold among all GeneSight-guided compared to all TAU subjects (p = 0.004), and overall, the guided group had a 53% greater improvement in depressive symptoms (p = 0.0002), a 1.7-fold relative improvement in response (p = 0.01), and a number needed to treat for one clinical response above that seen in the TAU group of 6.07. PMID:27606312

  18. Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial.

    PubMed

    Williams, Leanne M; Korgaonkar, Mayuresh S; Song, Yun C; Paton, Rebecca; Eagles, Sarah; Goldstein-Piekarski, Andrea; Grieve, Stuart M; Harris, Anthony W F; Usherwood, Tim; Etkin, Amit

    2015-09-01

    Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test-retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin-norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen's d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward 'normalization' post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to

  19. Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial

    PubMed Central

    Williams, Leanne M; Korgaonkar, Mayuresh S; Song, Yun C; Paton, Rebecca; Eagles, Sarah; Goldstein-Piekarski, Andrea; Grieve, Stuart M; Harris, Anthony W F; Usherwood, Tim; Etkin, Amit

    2015-01-01

    Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test–retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin–norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen's d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward ‘normalization' post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to

  20. Referral for psychological therapy of people with long term conditions improves adherence to antidepressants and reduces emergency department attendance: Controlled before and after study

    PubMed Central

    de Lusignan, Simon; Chan, Tom; Tejerina Arreal, Maria C.; Parry, Glenys; Dent-Brown, Kim; Kendrick, Tony

    2013-01-01

    Background Referral to psychological therapies is recommended for people with common mental health problems (CMHP) however its impact on healthcare utilisation in people with long term conditions (LTCs) is not known. Method Routinely collected primary care, psychological therapy clinic and hospital data were extracted for the registered population of 20 practices (N = 121199). These data were linked using the SAPREL (Secure and Private Record Linkage) method. We linked the 1118 people referred to psychological therapies with 6711 controls, matched for age, gender and practice. We compared utilisation of healthcare resources by people with LTCs, 6 months before and after referral, and conducted a controlled before and after study to compare health utilisation with controls. We made the assumption that collection of a greater number of repeat prescriptions for antidepressants was associated with greater adherence. Results Overall 21.8% of people with an LTC had CMHP vs. 18.8% without (p < 0.001). People with LTCs before referral were more likely to use health care resources (2-tailed t-test p < 0.001). Cases with LTCs showed referral to the psychological therapies clinic was associated with increased antidepressant medication prescribing (mean differences 0.62, p < 0.001) and less use of emergency department than controls (mean difference −0.21, p = 0.003). Conclusions Referral to improved access to psychological therapies (IAPT) services appears of value to people with LTC. It is associated with the issue of a greater number of prescriptions for anti-depressant medicines and less use of emergency services. Further studies are needed to explore bed occupancy and outpatient attendance. PMID:23639304

  1. Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice.

    PubMed

    Nguyen, Linda; Matsumoto, Rae R

    2015-12-15

    Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug. PMID:25804358

  2. Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA).

    PubMed

    Yeh, Ta-Chuan; Kao, Lien-Cheng; Tzeng, Nian-Sheng; Kuo, Terry B J; Huang, San-Yuan; Chang, Chuan-Chia; Chang, Hsin-An

    2016-01-01

    Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20-65 years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6 weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n=29 for agomelatine, n=27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone. PMID:26216863

  3. Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study

    PubMed Central

    Hughes, Shannon; Cohen, David; Jaggi, Rachel

    2014-01-01

    Objective To examine the degree of concordance in reporting serious adverse events (SAEs) from antidepressant and antipsychotic drug trials among journal articles and clinical trial summaries, and to categorise types of discrepancies. Design Cross-sectional study of summaries of all antidepressant and antipsychotic trials included in an online trial registry and their first associated stand-alone journal articles. Setting Clinicalstudyresults.org, sponsored by Pharmaceutical Research and Manufacturers of America; clinicaltrials.gov, administered by the US National Institutes of Health. Main outcome measure 3 coders extracted data on the numbers and types of SAEs. Results 244 trial summaries for six antidepressant and antipsychotic drugs were retrieved, 142 (58.2%) listing an associated article. Of 1608 SAEs in drug-treated participants according to trial summaries, 694 (43.2%) did not appear in associated articles. Nearly 60% of SAEs counted in articles and 41% in trial summaries had no description. Most cases of death (62.3%) and suicide (53.3%) were not reported in articles. Half or more of the 142 pairs were discordant in reporting the number (49.3%) or description (67.6%) of SAEs. These discrepancies resulted from journal articles’ (1) omission of complete SAE data, (2) reporting acute phase study results only and (3) more restrictive reporting criteria. Trial summaries with zero SAE were 2.35 (95% CI, 1.58 to 3.49; p<0.001) times more likely to be published with no discrepancy in their associated journal article. Since clinicalstudyresults.org was removed from the Internet in 2011, only 7.8% of retrieved trial summaries appear with results on clinicaltrials.gov. Conclusions Substantial discrepancies exist in SAE data found in journal articles and registered summaries of antidepressant and antipsychotic drug trials. Two main scientific sources accessible to clinicians and researchers are limited by incomplete, ambiguous and inconsistent reporting. Access to

  4. Early identification of non-responding locally advanced breast tumors receiving neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Van de Giessen, Martijn; Schaafsma, Boudewijn E.; Charehbili, Ayoub; Smit, Vincent T. H. B. M.; Kroep, Judith R.; Lelieveldt, Boudewijn P. F.; Liefers, Gerrit-Jan; Chan, Alan; Löwik, Clemens W. G. M.; Dijkstra, Jouke; van de Velde, Cornelis J. H.; Wasser, Martin N. J. M.; Vahrmeijer, Alexander L.

    2015-02-01

    Diffuse optical spectroscopy (DOS) may be advantageous for monitoring tumor response during chemotherapy treatment, particularly in the early treatment stages. In this paper we perform a second analysis on the data of a clinical trial with 25 breast cancer patients that received neoadjuvant chemotherapy. Patients were monitored using delayed contrast enhanced MRI and additionally with diffuse optical spectroscopy at baseline, after 1 cycle of chemotherapy, halfway therapy and before surgery. In this analysis hemoglobin content between tumor tissue and healthy tissue of the same breast is compared on all four monitoring time points. Furthermore, the predictive power of the tumor-healthy tissue difference of HbO2 for non-responder prediction is assessed. The difference in HbO2 content between tumor and healthy tissue was statistically significantly higher in responding tumors than in non-responding tumors at baseline (10.88 vs -0.57 μM, P=0.014) and after one cycle of chemotherapy (6.45 vs -1.31 μM, P=0.048). Before surgery this difference had diminished. In the data of this study, classification on the HbO2 difference between tumor and healthy tissue was able to predict tumor (non-)response at baseline and after 1 cycle with an area-under-curve of 0.95 and 0.88, respectively. While this result suggests that tumor response can be predicted before chemotherapy onset, one should be very careful with interpreting these results. A larger patient population is needed to confirm this finding.

  5. Antidepressants modulate glycine action in rat hippocampus.

    PubMed

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-12-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current. PMID:26730381

  6. Antidepressants modulate glycine action in rat hippocampus

    PubMed Central

    Chang, Hyun-Kyung; Kim, Khae Hawn; Kang, Ki-Woon; Kang, Yoo-Jin; Kim, Tae-Wook; Park, Hun-Kyung; Kim, Sung-Eun; Kim, Chang-Ju

    2015-01-01

    Antidepressants are drugs that relieve symptoms of depressive disorders. Fluoxetine, tianeptine, and milnacipran are different types of antidepressants, and they have widely been used for relieving of depression symptoms. In the present study, the effects of fluoxetine, tianeptine, and milnacipran on the glycine-induced ion current by nystatin-perforated patch clamp and on the amplitude of field potential in the hippocampal CA1 region by multichannel extracellular recording, MED64, system, were studied. In the present results, fluoxetine, tianeptine, and milnacipran reduced glycine-induced ion current in the hippocampal CA1 neurons in nystatin-perforated patch clamp method. These drugs enhanced the amplitude of the field potential in the hippocampal CA1 region in MED64 system. These results suggest that antidepressants may increase neuronal activity by enhancing field potential through inhibition on glycine-induced ion current. PMID:26730381

  7. Antidepressants and cardiovascular adverse events: A narrative review

    PubMed Central

    Nezafati, Mohammad Hassan; Vojdanparast, Mohammad; Nezafati, Pouya

    2015-01-01

    BACKGROUND Major depression or deterioration of previous mood disorders is a common adverse consequence of coronary heart disease, heart failure, and cardiac revascularization procedures. Therefore, treatment of depression is expected to result in improvement of mood condition in these patients. Despite demonstrated effects of anti-depressive treatment in heart disease patients, the use of some antidepressants have shown to be associated with some adverse cardiac and non-cardiac events. In this narrative review, the authors aimed to first assess the findings of published studies on beneficial and also harmful effects of different types of antidepressants used in patients with heart diseases. Finally, a new categorization for selecting antidepressants according to their cardiovascular effects was described. METHODS Using PubMed, Web of Science, SCOPUS, Index Copernicus, CINAHL, and Cochrane Database, we identified studies designed to evaluate the effects of depression and also using antidepressants on cardiovascular outcome. A 40 studies were finally assessed systematically. Among those eligible studies, 14 were cohort or historical cohort studies, 15 were randomized clinical trial, 4 were retrospective were case-control studies, 3 were meta-analyses and 2 animal studies, and 2 case studies. RESULTS According to the current review, we recommend to divide antidepressants into three categories based on the severity of cardiovascular adverse consequences including (1) the safest drugs including those drugs with cardio-protective effects on ventricular function, as well as cardiac conductive system including selective serotonin reuptake inhibitors, (2) neutralized drugs with no evidenced effects on cardiovascular system including serotonin-norepinephrine reuptake inhibitors, and (3) harmful drugs with adverse effects on cardiac function, hemodynamic stability, and heart rate variability including tricyclic antidepressants, serotonin antagonist and reuptake inhibitors

  8. An Open Trial of Intensive Family Based Cognitive-Behavioral Therapy in Youth with Obsessive-Compulsive Disorder Who Are Medication Partial Responders or Nonresponders

    ERIC Educational Resources Information Center

    Storch, Eric A.; Lehmkuhl, Heather D.; Ricketts, Emily; Geffken, Gary R.; Marien, Wendi; Murphy, Tanya K.

    2010-01-01

    This study reports an open-trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD). Thirty primarily Caucasian youth with OCD (range = 7-19 years; 15 girls) who were partial responders or nonresponders to two or more medication trials that were delivered either serially or…

  9. Visual Motor Integration as a Screener for Responders and Non-Responders in Preschool and Early School Years: Implications for Inclusive Assessment in Oman

    ERIC Educational Resources Information Center

    Emam, Mahmoud Mohamed; Kazem, Ali Mahdi

    2016-01-01

    Visual motor integration (VMI) is the ability of the eyes and hands to work together in smooth, efficient patterns. In Oman, there are few effective methods to assess VMI skills in children in inclusive settings. The current study investigated the performance of preschool and early school years responders and non-responders on a VMI test. The full…

  10. Review of Evidence for Use of Antidepressants in Bipolar Depression

    PubMed Central

    McInerney, Shane J.

    2014-01-01

    Objective: Depressive episodes predominate over the course of bipolar disorder and cause considerable functional impairment. Antidepressants are frequently prescribed in the treatment of bipolar depression, despite concerns about efficacy and risk of switching to mania. This review provides a critical examination of the evidence for and against the use of antidepressants in bipolar depression. Data Sources: English-language peer-reviewed literature and evidence-based guidelines published between January 1, 1980, and March 2014, were identified using PubMed, MEDLINE, PsycINFO/PsycLIT, and EMBASE. All searches contained the terms antidepressants, bipolar depression, depressive episodes in bipolar disorder, and treatment guidelines for bipolar depression. Meta-analyses, randomized controlled trials, systematic reviews, and practice guidelines were included. Bibliographies from these publications were used to identify additional articles of interest. Data Extraction: Studies involving treatment of bipolar depression with antidepressant monotherapy, adjunctive use of antidepressant with a mood stabilizer, and meta-analysis of such studies combined were reviewed. Conclusions: The body of evidence on the use of antidepressant monotherapy to treat patients with bipolar depression is contentious, but the recommendations from evidence-based guidelines do not support antidepressant monotherapy for bipolar depression. Only when mood stabilizer or atypical antipsychotic monotherapy has failed should adjunctive treatment with an antidepressant be considered. PMID:25667812

  11. Effects of Persisting Emotional Impact from Child Abuse and Norepinephrine Transporter Genetic Variation on Antidepressant Efficacy in Major Depression: A Pilot Study

    PubMed Central

    Singh, Ajeet Bhagat; Bousman, Chad A.; Ng, Chee Hong; Byron, Keith; Berk, Michael

    2015-01-01

    Objective Previous studies suggest child abuse and serotonergic polymorphism influence depression susceptibility and anti-depressant efficacy. Polymorphisms of the norepinephrine transporter (NET) may also be involved. Research in the area is possibly clouded by under reporting of abuse in researcher trials. Methods Adults (n=51) with major depressive disorder has 8 weeks treatment with escitalopram or venlafaxine. Abuse history was obtained, the ongoing emotional impact of which was measured with the 15-item impact of event scale (IES-15). The 17-item Hamilton Depression Rating Scale (HDRS) was applied serially. Two NET polymorphisms (rs2242446 and rs5569) were assayed, blinded to HDRS ratings and abuse history. Results No subjects reporting abuse with high impact in adulthood (IES-15 ≥26, n=12) remitted; whereas 77% reporting low impact (IES-15 <26; n=26) remitted (p<0.001). Subjects reporting high impact abuse (n=12) had a 50-fold (95% confidence interval=4.85–514.6) greater odds of carrying rs2242446-TT genotype, but the small sample size leaves this finding vulnerable to type I error. Conclusion The level of persisting impact of child abuse appears relevant to antidepressant efficacy, with susceptibility to such possibly being influence by NET rs2242446 polymorphism. Larger studies may be merited to expand on this pilot level finding given potential for biomarker utility. PMID:25912538

  12. Synthesis and Behavioral Studies of Chiral Cyclopropanes as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile. Part III.

    PubMed

    Onajole, Oluseye K; Vallerini, Gian Paolo; Eaton, J Brek; Lukas, Ronald J; Brunner, Dani; Caldarone, Barbara J; Kozikowski, Alan P

    2016-06-15

    We report the synthesis and biological characterization of novel derivatives of 3-[(1-methyl-2(S)-pyrrolidinyl)methoxy]-5-cyclopropylpyridine (4a-f and 5) as potent and highly selective α4β2-nicotinic acetylcholine receptor (nAChR) full or partial agonists. A systematic structure-activity study was carried out on the previously described compound 3b, particularly concerning its (2-methoxyethyl)cyclopropyl side-chain, in an effort to improve its metabolic stability while maintaining receptor selectivity. Compound 4d exhibited very similar subnanomolar binding affinity for α4β2- and α4β2*-nAChRs compared to 3b, and it showed excellent potency in activating high-sensitivity (HS) α4β2-nAChRs with an EC50 value of 8.2 nM. Testing of 4d in the SmartCube assay revealed that the compound has a combined antidepressant plus antipsychotic signature. In the forced swim test at a dose of 30 mg/kg given intraperitoneally, 4d was found to be as efficacious as sertraline, thus providing evidence of the potential use of the compound as an antidepressant. Additional promise for use of 4d in humans comes from pharmacokinetic studies in mice indicating brain penetration, and additional assays show compound stability in the presence of human microsomes and hepatocytes. Thus, 4d has a very favorable preclinical drug profile. PMID:27035276

  13. Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

    PubMed Central

    Hanson, Nicola D; Owens, Michael J; Nemeroff, Charles B

    2011-01-01

    The neurogenesis hypothesis of depression posits (1) that neurogenesis in the subgranular zone of the dentate gyrus is regulated negatively by stressful experiences and positively by treatment with antidepressant drugs and (2) that alterations in the rate of neurogenesis play a fundamental role in the pathology and treatment of major depression. This hypothesis is supported by important experimental observations, but is challenged by equally compelling contradictory reports. This review summarizes the phenomenon of adult hippocampal neurogenesis, the initial and continued evidence leading to the development of the neurogenesis hypothesis of depression, and the recent studies that have disputed and/or qualified those findings, to conclude that it can be affected by stress and antidepressants under certain conditions, but that these effects do not appear in all cases of psychological stress, depression, and antidepressant treatment. PMID:21937982

  14. Abuse and misuse of antidepressants

    PubMed Central

    Evans, Elizabeth A; Sullivan, Maria A

    2014-01-01

    Background Rates of prescription drug abuse have reached epidemic proportions. Large-scale epidemiologic surveys of this under-recognized clinical problem have not included antidepressants despite their contribution to morbidity and mortality. The purpose of this review is to look specifically at the misuse of antidepressants and how this behavior may fit into the growing crisis of nonmedical use of prescription drugs. Methods We conducted a comprehensive search on PubMed, Medline, and PsycINFO using the search terms “antidepressant”, “abuse”, “misuse”, “nonmedical use”, “dependence”, and “addiction”, as well as individual antidepressant classes (eg, “SSRI”) and individual antidepressants (eg, “fluoxetine”) in various combinations, to identify articles of antidepressant misuse and abuse. Results A small but growing literature on the misuse and abuse of antidepressants consists largely of case reports. Most cases of antidepressant abuse have occurred in individuals with comorbid substance use and mood disorders. The most commonly reported motivation for abuse is to achieve a psychostimulant-like effect. Antidepressants are abused at high doses and via a variety of routes of administration (eg, intranasal, intravenous). Negative consequences vary based upon antidepressant class and pharmacology, but these have included seizures, confusion, and psychotic-like symptoms. Conclusion The majority of individuals prescribed antidepressants do not misuse the medication. However, certain classes of antidepressants do carry abuse potential. Vulnerable patient populations include those with a history of substance abuse and those in controlled environments. Warning signs include the presence of aberrant behaviors. Physicians should include antidepressants when screening for risky prescription medication use. When antidepressant misuse is detected, a thoughtful treatment plan, including referral to an addiction specialist, should be developed and

  15. Potential Antidepressant Constituents of Nigella sativa Seeds

    PubMed Central

    Elkhayat, Ehab S.; Alorainy, Mohammad S.; El-Ashmawy, Ibrahim M.; Fat’hi, Shawkat

    2016-01-01

    Background: Nigella sativa Linn. is well known seed in the Middle East, Asia, and the Far East as a natural remedy for many ailments and as a flavoring agent proclaimed medicinal usage dating back to the ancient Egyptians, Greeks, and Romans. An authentic saying of the Prophet Muhammad (Peace Be Upon Him) about black seed is also quoted in Al-Bukhari. Objective: This study was carried out to evaluate the antidepressant effect and isolate the potential antidepressant constituents of the polar extract of N. sativa seeds. Materials and Methods: The antidepressant effect was evaluated through the immobility duration in tail suspension and forced swim tests (FSTs). Albino mice were orally treated with N. sativa polar extract and its RP-18 column chromatography fractions (50 and 100 mg/kg,). Results: The polar extract and two of its sub-fractions were significantly able to decrease the immobility time of mice when subjected to both tail suspension and FSTs, the effects are comparable to standard drug (Sertraline, 5 mg/kg). However, these treatments did not affect the number of crossings and rearing in the open field test. Phytochemical investigation of the two active fractions led to the isolation of quercetin-3-O-α-L-rhamnopyranoside 1, quercetin-7-O-β-D-gluco- pyranoside 2, tauroside E 3, and sapindoside B as the potential antidepressant constituents. SUMMARY Phytochemical and biological evaluation the antidepressant constituents in Nigella sativa using the tail suspension and forced swim methods afforded the isolation and identification of quercetin-3-O-α-L rhamnopyranoside, quercetin-7-O-β-D gluco pyranoside, tauroside E, and sapindoside B as the potential antidepressant constituents in the polar extract of N. sativa. The isolated compounds were identified through extensive NMR analysis (1D, 2D, ESI MS). Abbreviations used: TST: Tail suspension test, FST: Forced swim test, OFT: An Open field test PMID:27041854

  16. [Mirtazapine--an antidepressant].

    PubMed

    Landowski, Jerzy

    2002-01-01

    The pharmacological properties and clinical value of mirtazapine has been presented, based on a literature review. It is concluded that mirtazapine has syndromolytic anti-depressive actions towards syndromes of various clinical picture and intensity. It is particularly highly recommended in the treatment of depressive disorders with insomnia, anxiety and body-weight reduction. It is a safe drug, which can be used, in long-term supportive treatment. PMID:12647431

  17. Antidepressants during pregnancy and postpartum hemorrhage: a systematic review.

    PubMed

    Bruning, Andrea H L; Heller, Hanna M; Kieviet, Noera; Bakker, Petra C A M; de Groot, Christianne J M; Dolman, Koert M; Honig, Adriaan

    2015-06-01

    The use of antidepressants in pregnancy is increasing. Concerns have risen about the use of antidepressants during pregnancy and the risk of postpartum hemorrhage (PPH). The aim of this systematic review is to summarize evidence on the association between use of antidepressants during pregnancy and the risk of PPH. An Embase and Pubmed search was conducted. English and Dutch language studies reporting original data regarding bleeding after delivery associated with exposure to antidepressants during pregnancy were selected. Quality appraisal was conducted using the Newcastle Ottawa Scale (NOS). Out of 81 citations, 4 studies were included. Based on the NOS, 3 were considered of good quality and 1 was considered of satisfactory quality. Two studies reported an increased incidence of PPH in women who used antidepressants during pregnancy. The other two studies identified no overall increased risk of PPH among pregnant women exposed to antidepressants. The existing evidence remains inconclusive whether use of antidepressants during pregnancy is associated with an increased risk of postpartum hemorrhage. If there is such an association the absolute increased risk will be low and the clinical relevance needs to be further examined. PMID:25845914

  18. A Qualitative Analysis of the Perception of Stigma Among Latinos Receiving Antidepressants

    PubMed Central

    Interian, Alejandro; Martinez, Igda E.; Guarnaccia, Peter J.; Vega, William A.; Escobar, Javier I.

    2008-01-01

    Objective This study sought to describe the role of stigma in antidepressant adherence among Latinos. Methods The study utilized data generated from six focus groups of Latino outpatients receiving antidepressants (N=30). By using a grounded theory approach, qualitative analysis focused specifically on the role of stigma in antidepressant treatment, as well as salient Latino values. Results Perceptions of stigma were related to both the diagnosis of depression and use of antidepressant medication. Qualitative analyses showed that antidepressant use was seen as implying more severe illness, weakness or failure to cope with problems, and being under the effects of a drug. Reports of stigma were also related to social consequences. Also, the perceived negative attributes of antidepressant use were at odds with self-perceived cultural values. Conclusions Stigma was a prominent concern among Latinos receiving antidepressants, and stigma often affected adherence. Furthermore, culture is likely to play an important role in the communication of stigma and its associated complications. PMID:18048562

  19. Duration and compliance with antidepressant treatment in immigrant and native-born populations in Spain: a four year follow-up descriptive study

    PubMed Central

    2012-01-01

    Background Non-compliance with antidepressant treatment continues to be a complex problem in mental health care. In immigrant populations non-compliance is one of several barriers to adequate management of mental illness; some data suggest greater difficulties in adhering to pharmacological treatment in these groups and an increased risk of therapeutic failure. The aim of this study is to assess differences in the duration and compliance with antidepressant treatment among immigrants and natives in a Spanish health region. Methods Population-based (n=206,603), retrospective cohort study including all subjects prescribed ADT between 2007 and 2009 and recorded in the national pharmacy claims database. Compliance was considered adequate when the duration was longer than 4months and when patients withdrew more than 80% of the packs required. Results 5334 subjects (8.5% of them being immigrants) initiated ADT. Half of the immigrants abandoned treatment during the second month (median for natives=3months). Of the immigrants who continued, only 29.5% presented good compliance (compared with 38.8% in natives). The estimated risk of abandoning/ending treatment in the immigrant group compared with the native group, adjusted for age and sex, was 1.28 (95%CI 1.16-1.42). Conclusions In the region under study, immigrants of all origins present higher percentages of early discontinuation of ADT and lower median treatment durations than the native population. Although this is a complex, multifactor situation, the finding of differences between natives and immigrants in the same region suggests the need to investigate the causes in greater depth and to introduce new strategies and interventions in this population group. PMID:22469197

  20. Defeating cancer with antidepressants

    PubMed Central

    Lieb, J

    2008-01-01

    Prostaglandins are ephemeral, infinitesimal signallers self-regulating every cell in the body, including those sub-serving mood and immunity. At first, they were perceived as a master switch, but now are believed to regulate every component of cellular micro-anatomy and physiology, including those of the organelles, cytoskeleton, proteins, enzymes, nucleic acids and mitochondria. Prostaglandins are responsible, paradoxically, for cell function and dysfunction. Excessive prostaglandin synthesis depresses immune function and may induce cancer. An ideal anti-cancer agent would inhibit prostaglandins in such a manner as to shut down the pathogenesis of cancer. In this paper, I will show that antidepressants have such properties. PMID:22275973

  1. Liquid-Phase Microextraction and Gas Chromatographic-Mass Spectrometric Analysis of Antidepressants in Vitreous Humor: Study of Matrix Effect of Human and Bovine Vitreous and Saline Solution.

    PubMed

    Dos Santos, Marcelo Filonzi; Yamada, Adrian; Seulin, Saskia Carolina; Leyton, Vilma; Pasqualucci, Carlos Augusto Gonçalves; Muñoz, Daniel Romero; Yonamine, Mauricio

    2016-04-01

    In forensic bioanalytical methods, there is a general agreement that calibrators should be prepared by fortifying analytes in matrix-based blank samples (matrix-based). However, in the case of vitreous humor (VH), the collection of blank samples for the validation and for routine analysis would require the availability of many cadavers. Besides the difficulty of obtaining enough blank VH, this procedure could also represent an ethical issue. Here, a study of matrix effect was performed taking into consideration human and bovine vitreous and saline solution (SS) (NaCl 0.9%). Tricyclic antidepressants [amitriptyline (AMI), nortriptyline (NTR), imipramine (IMI) and desipramine (DES)] were used as model analytes and were extracted from samples by means of liquid-phase microextraction and detected by gas chromatography-mass spectrometry. Samples of human and bovine VH and SS were prepared in six different concentrations of antidepressants (5, 40, 80, 120, 160 and 200 ng/mL) and were analyzed. Relative matrix effect was evaluated by applying a two-tailed homoscedastic Student's t-test, comparing the results obtained with the set of data obtained with human VH and bovine VH and SS. No significant matrix effect was found for AMI and NTR in the three evaluated matrices. However, a great variability was observed for IMI and DES for all matrices. Once compatibilities among the matrices were demonstrated, the method was fully validated for AMI and NTR in SS. The method was applied to six VH samples deriving from real cases whose femoral whole blood (FWB) was analyzed by a previously published method. An average ratio (VH/FWB) of ∼0.1 was found for both compounds. PMID:26755541

  2. Future Antidepressant Targets: Neurotrophic Factors and Related Signaling Cascades

    PubMed Central

    Schmidt, Heath D.; Banasr, Mounira; Duman, Ronald S.

    2009-01-01

    Preclinical and clinical studies demonstrate that neurotrophic factors play critical roles in the etiology and treatment of depression. While the mechanisms underlying the therapeutic efficacy of antidepressants remain unknown, increasing evidence supports a role for increased trophic support in the treatment of depression. Furthermore, antidepressants block or reverse stress-induced down regulation of neurotrophic factor expression in limbic and cortical nuclei involved in the underlying pathophysiology of depression. Thus, components of neurotrophic factor-mediated signaling cascades or the signal transduction pathways that regulate neurotrophic factor expression may provide additional targets for the development of novel, more efficacious antidepressant drugs. PMID:19802372

  3. Solving the Antidepressant Efficacy Question? Effect Sizes in Major Depressive Disorder

    PubMed Central

    Vöhringer, Paul A.; Ghaemi, S. Nassir

    2011-01-01

    Background Numerous reviews and meta-analyses of the antidepressant literature in MDD, both acute and maintenance, have been published, some claiming that antidepressants are mostly ineffective, others that they are mostly effective, either in acute or maintenance treatment. Objective To review and critique last and most notable antidepressant MDD studies, and conduct our own reanalysis of the FDA database studies specifically analyzed by Kirsch and colleagues. Methods We gather effect estimates of each MDD study. In our reanalysis of Kirsch and colleagues, we correct those analyses for a statistical floor effect, so that relative (instead of absolute) effect size differences are calculated. Results Our reanalysis shows that antidepressant benefit is seen not only in severe depression, but also in moderate depression while confirming lack of benefit of antidepressants over placebo in mild depression. Relative antidepressant versus placebo benefit increased linearly from 5% in mild depression to 12% in moderate depression to 16% in severe depression. The claim that antidepressants are completely ineffective, or even harmful, in maintenance treatment studies involves unawareness of the enriched design effect, which, in that analysis, was used to ensure placebo efficacy. The same problem exists for the standard interpretation of those studies, though: they do not prove antidepressant efficacy either, since they are biased in favor of antidepressants. Conclusions In sum, we would conclude that antidepressants are effective for acute depressive episodes that are moderate to severe, but not in mild depression. One can turn the attention-getting conclusions of the review by Kirsch and associates around: Instead of concluding that antidepressants are ineffective acutely except for the most extreme depressive episodes, correction for the statistical floor effect proves that antidepressants are effective acutely except for the mildest depressive episodes. These

  4. A Comparison of Community College Responders and Nonresponders to the VEDS Student Follow-Up Survey.

    ERIC Educational Resources Information Center

    Carifio, James; And Others

    1991-01-01

    A survey of respondents and nonrespondents to the Vocational Education Data System's follow-up survey of Massachusetts community college graduates was designed to measure response bias. The survey investigated employment patterns, wages, and degree of job relatedness. Results suggest original data was biased, if at all, toward underestimation, not…

  5. Understanding Faculty Survey Nonrespondents: Their Characteristics, Organizational Citizenship Behaviors, Workplace Attitudes, and Reasons for Nonparticipation

    ERIC Educational Resources Information Center

    Mathews, Kiernan Robert

    2013-01-01

    College and university administrators frequently survey their faculty to inform decisions affecting the academic workplace. Higher education researchers, too, rely heavily on survey methodologies in their scholarly work. Survey response rates, however, have been declining steadily for decades, and when nonrespondents and respondents systematically…

  6. Interaction of tricyclic antidepressants with cholestyramine in vitro.

    PubMed

    Bailey, D N; Coffee, J J; Anderson, B; Manoguerra, A S

    1992-08-01

    The adsorption of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline onto cholestyramine was demonstrated in vitro with use of 1.2 mol/L HCl at 37 degrees C to simulate gastric fluid. Binding to cholestyramine was approximately 80% for each of the tricyclic antidepressants, and this was about the same degree of binding noted with a nonpharmaceutical, non-ionic resin widely used in the diagnostic toxicology laboratory (Amberlite XAD-2). In contrast, five other non-antidepressants (acetaminophen, chlordiazepoxide, procainamide, quinidine, and theophylline) showed only minimal binding to cholestyramine under these conditions. Activated charcoal completely bound all drugs studied. These findings suggest that cholestyramine should be used with caution in patients receiving tricyclic antidepressants. They also suggest that cholestyramine may be a potentially useful adjunctive therapy in treatment of overdose with the tricyclic antidepressants. PMID:1519310

  7. Antidepressant-related sexual dysfunction - perspectives from neuroimaging.

    PubMed

    Graf, Heiko; Walter, Martin; Metzger, Coraline D; Abler, Birgit

    2014-06-01

    Sexual dysfunction is not only a common symptom in major depression but also a frequent side-effect of antidepressant medication, mainly of the selective serotonin reuptake-inhibitors (SSRI) that are often prescribed as a first line treatment option. Despite of the increasing incidence and prescription rates, neuronal mechanisms underlying SSRI-related sexual dysfunction are poorly understood and investigations on this topic are scarce. Neuroimaging techniques, mainly functional magnetic resonance imaging (fMRI), provide a feasible approach to investigate these mechanisms since SSRI-related sexual dysfunction is most likely related to central nervous processes. This review summarizes the recent literature regarding the basic clinical findings and imaging correlates of antidepressant-related sexual dysfunction linking brain regions and networks potentially involved to phases and subcomponents of sexual processing and antidepressant action. In particular, fMRI studies on SSRI antidepressants including paroxetine and SNRIs including bupropion are highlighted. PMID:24333547

  8. Neuroimmune endocrine effects of antidepressants

    PubMed Central

    Antonioli, Marco; Rybka, Joanna; Carvalho, Livia A

    2012-01-01

    Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models. PMID:22347798

  9. [Withdrawal syndrome from antidepressive drugs. Report of 5 cases].

    PubMed

    Lejoyeux, M; Rodière-Rein, C; Adès, J

    1992-01-01

    Antidepressant withdrawal symptoms, following abrupt or gradual discontinuation of antidepressants, include general somatic distress (flu-like syndromes, gastro-intestinal disturbances, myalgias, headache, chills, weakness and rhinorrhea), anxiety, agitation, sleep disturbances, movement disorders, cardiac arrhythmias, delirium and manic reactions. Two cases of delirium, an hypomanic reaction and two general distress and movement disorders are reported. Cases 1 and 2 required admission to a general hospital. The etiology of the delirium was difficult to assess as long as the clinicians did not know that patients were taking antidepressants. Case 3 corresponds to the paradoxical activation following antidepressant interruption. Cases 4 and 5 constitutes light withdrawal syndromes. Most of cases are probably unrecognized. These cases reflect the importance in daily practice of the phenomena. It can be concluded from our study that: antidepressants must not be abruptly discontinued when a somatic disease appears. When a patient treated with a psychotropic drug develops delirium, the withdrawal of antidepressant must be suspected and the prescribing physician contacted to know what kind of psychoactive medication was prescribed. PMID:1299596

  10. Chemistry and Behavioral Studies Identify Chiral Cyclopropanes as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile

    PubMed Central

    Zhang, Hankun; Tückmantel, Werner; Eaton, J. Brek; Yuen, Po-wai; Yu, Li-Fang; Bajjuri, Krishna Mohan; Fedolak, Allison; Wang, Daguang; Ghavami, Afshin; Caldarone, Barbara; Paterson, Neil E.; Lowe, David A.; Brunner, Daniela; Lukas, Ronald J.; Kozikowski, Alan P.

    2012-01-01

    Despite their discovery in the early 20th century and intensive study over the last twenty years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing α4β2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity, while acting as partial agonists at α4β2-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening towards other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other α4β2-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression. PMID:22171543

  11. Serum metabonomics study of anti-depressive effect of Xiao-Chai-Hu-Tang on rat model of chronic unpredictable mild stress.

    PubMed

    Xiong, Zhili; Yang, Jie; Huang, Yue; Zhang, Kuo; Bo, Yunhai; Lu, Xiumei; Su, Guangyue; Ma, Jie; Yang, Jingyu; Zhao, Longshan; Wu, Chunfu

    2016-09-01

    Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment. PMID:27398633

  12. A 1H-NMR-Based Metabonomic Study on the Anti-Depressive Effect of the Total Alkaloid of Corydalis Rhizoma.

    PubMed

    Wu, Hongwei; Wang, Peng; Liu, Mengting; Tang, Liying; Fang, Jing; Zhao, Ye; Zhang, Yi; Li, Defeng; Xu, Haiyu; Yang, Hongjun

    2015-01-01

    Corydalis Rhizoma, named YuanHu in China, is the dried tuber of Corydalis yanhusuo W.T. Wang which is used in Traditional Chinese Medicine for pain relief and blood activation. Previous pharmacological studies showed that apart from analgesics, the alkaloids from YuanHu may be useful in the therapy of depression by acting on the GABA, dopamine and benzodiazepine receptors. In this study, the antidepressive effect of the total alkaloid of YuanHu (YHTA) was investigated in a chronic unpredictable mild stress (CUMS) rat model using 1H-NMR-based metabonomics. Plasma metabolic profiles were analyzed and multivariate data analysis was applied to discover the metabolic biomarkers in CUMS rats. Thirteen biomarkers of CUMS-introduced depression were identified, which are myo-inositol, glycerol, glycine, creatine, glutamine, glutamate, β-glucose, α-glucose, acetoacetate, 3-hydroxybutyrate, leucine and unsaturated lipids (L7, L9). Moreover, a metabolic network of the potential biomarkers in plasma perturbed by CUMS was detected. After YHTA treatment, clear separation between the model group and YHTA-treated group was achieved. The levels of all the abnormal metabolites mentioned above showed a tendency of restoration to normal levels. The results demonstrated the therapeutic efficacy of YHTA against depression and suggested that NMR-based metabolomics can provide a simple and easy tool for the evaluation of herbal therapeutics. PMID:26035102

  13. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.

    PubMed

    Reimherr, F W; Chouinard, G; Cohn, C K; Cole, J O; Itil, T M; LaPierre, Y D; Masco, H L; Mendels, J

    1990-12-01

    A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo. PMID:2258378

  14. Suicide and antidepressants: what current evidence indicates.

    PubMed

    Nischal, Anil; Tripathi, Adarsh; Nischal, Anuradha; Trivedi, J K

    2012-01-01

    The documented efficacy and long-term benefit of antidepressants in patients with recurrent forms of severe anxiety or depressive disorders support their use in those individuals with these disorders, who experience suicidal thoughts or behavior. In general, it is assumed that antidepressants are beneficial for all symptoms of depression, including suicidality. However, some evidence suggests that Selective Serotonin Reuptake Inhibitors [SSRIs] may cause worsening of suicidal ideas in vulnerable patients. Systematic reviews and pooled analysis of experimental, observational, and epidemiological studies have investigated the use of SSRIs and their association with suicidality. Taking account of the methodological limitations of these studies, the current evidence fails to provide a clear relationship between their use and risk of suicidality in adults. However, in children and adolescents, there appears to be a bit of increased risk of suicidal ideations and attempts, but not of completed suicides. This risk can be anticipated and managed clinically. Clinicians are, therefore, advised to maintain a close follow-up during the initial treatment periods and remain vigilant of this risk. This advisory, however, should not deter clinicians from the use of effective dosages of antidepressants for a sufficient period of time, in every age group of patients, when clinically needed, and if found suitable otherwise. PMID:22654381

  15. Suicide and Antidepressants: What Current Evidence Indicates

    PubMed Central

    Nischal, Anil; Tripathi, Adarsh; Nischal, Anuradha; Trivedi, J. K.

    2012-01-01

    The documented efficacy and long-term benefit of antidepressants in patients with recurrent forms of severe anxiety or depressive disorders support their use in those individuals with these disorders, who experience suicidal thoughts or behavior. In general, it is assumed that antidepressants are beneficial for all symptoms of depression, including suicidality. However, some evidence suggests that Selective Serotonin Reuptake Inhibitors [SSRIs] may cause worsening of suicidal ideas in vulnerable patients. Systematic reviews and pooled analysis of experimental, observational, and epidemiological studies have investigated the use of SSRIs and their association with suicidality. Taking account of the methodological limitations of these studies, the current evidence fails to provide a clear relationship between their use and risk of suicidality in adults. However, in children and adolescents, there appears to be a bit of increased risk of suicidal ideations and attempts, but not of completed suicides. This risk can be anticipated and managed clinically. Clinicians are, therefore, advised to maintain a close follow-up during the initial treatment periods and remain vigilant of this risk. This advisory, however, should not deter clinicians from the use of effective dosages of antidepressants for a sufficient period of time, in every age group of patients, when clinically needed, and if found suitable otherwise. PMID:22654381

  16. Milnacipran versus other antidepressive agents for depression

    PubMed Central

    Nakagawa, Atsuo; Watanabe, Norio; Omori, Ichiro M; Barbui, Corrado; Cipriani, Andrea; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

    2014-01-01

    Background Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care. Objectives To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression. Search methods The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were handsearched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. Selection criteria Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected. Data collection and analysis Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials. Main results A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis. Despite the size of this sample, the pooled 95% confidence intervals were

  17. Economic Effects of Anti-Depressant Usage on Elective Lumbar Fusion Surgery

    PubMed Central

    Sayadipour, Amirali; Kepler, Chrisopher K.; Mago, Rajnish; Certa, Kenneth M.; Rasouli, Mohammad R.; Vaccaro, Alexander R.; Albert, Todd J.; Anderson, David G.

    2016-01-01

    Background: It has been suggested, although not proven, that presence of concomitant psychiatric disorders may increase the inpatient costs for patients undergoing elective surgery. This study was designed to test the hypothesis that elective lumbar fusion surgery is more costly in patients with under treatment for depression. Methods: This is a retrospective case-control study of 142 patients who underwent elective lumbar fusion. Of those 142 patients, 41 patients were chronically using an antidepressant medication that considered as a “study group”, and 101 patients were not taking an antidepressant medication that considered as a “control group”. Data was collected for this cohort regarding antidepressant usage patient demographics, length of stay (LOS), age-adjusted Charlson comorbidity index scores and cost. Costs were compared between those with a concomitant antidepressant usage and those without antidepressant usage using multivariate analysis. Results: Patients using antidepressants and those with no history of antidepressant usage were similar in terms of gender, age and number of operative levels. The LOS demonstrated a non-significant trend towards longer stays in those using anti-depressants. Total charges, payments, variable costs and fixed costs were all higher in the antidepressant group but none of the differences reached statistical significance. Using Total Charges as the dependent variable, gender and having psychiatric comorbidities were retained independent variables. Use of an antidepressant was independently predictive of a 36% increase in Total Charges. Antidepressant usage as an independent variable also conferred a 22% increase in cost and predictive of a 19% increase in Fixed Cost. Male gender was predictive of a 30% increase in Total Charges. Conclusion: This study suggests use of antidepressant in patients who undergo elective spine fusion compared with control group is associated with increasing total cost and length of

  18. The Role of Metformin Response in Lipid Metabolism in Patients with Recent-Onset Type 2 Diabetes: HbA1c Level as a Criterion for Designating Patients as Responders or Nonresponders to Metformin

    PubMed Central

    Kashi, Zahra; Mahrooz, Abdolkarim; Kianmehr, Anvarsadat; Alizadeh, Ahad

    2016-01-01

    Background In this study, we investigated whether response to metformin, the most frequently drug for diabetes treatment, influences the therapeutic effects of antilipidemic medication in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Methods A total of 150 patients with T2DM were classified into two groups following 3 months of metformin therapy (1000 mg twice daily): responders (patients showing ≥1% reduction in HbA1c from baseline) and nonresponders (patients showing <1% reduction in HbA1c from baseline). The patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg and gemfibrozil 300 mg daily. Principal Findings HbA1c and fasting glucose levels were significantly different between baseline and 3 months among responders receiving atorvastatin; however, these differences were not statistically significant in nonresponders. Atherogenic ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic index of plasma; p = 0.004) decreased significantly in responders receiving atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin showed a significant increase in HDL-C levels but nonresponders receiving atorvastatin did not (p = 0.007). The multivariate model identified a significant association between metformin response (as the independent variable) and TG, TC, HDL-C and LDL-C (dependent variables; Wilk's λ = 0.927, p = 0.036). Conclusions Metformin response affects therapeutic outcomes of atorvastatin on atherogenic lipid markers in patients newly diagnosed with T2DM. Metformin has a greater impact on BMI in responders of metformin compared to nonresponders. Adoption of better therapeutic strategies for reducing atherogenic lipid markers may be necessary for metformin nonresponders. PMID:26978661

  19. Self-inhibiting action of nortriptylin's antidepressive effect at high plasma levels: a randomized double-blind study controlled by plasma concentrations in patients with endogenous depression.

    PubMed

    Kragh-Sorensen, P; Hansen, C E; Baastrup, P C; Hvidberg, E F

    1976-02-01

    Below the toxic plasma level of nortriptyline (NT) an upper therapeutic limit has been postulated in patients with endogenous depression. If so the clinical significance is obvious and a double-blind, randomized study was performed in order to solve this problem. Two groups of patients were controlled at different plasma levels (less than 150 ng/ml and less than 180 ng/ml). The degree of depression was rated weekly. Only about one third (n equals 24) of the patients originally included, were carried through the full protocol, the most prominent reason for drop out beeing spontaneous remission during an initial placebo period. After 4 weeks of NT treatment the majority in the high level group was still depressed, but the difference barely significant (P equals 5.5%). However, a randomized reduction of the plasma level among the patients at the high level resulted in a significant correlation to remission. Evaluation of the total material after 6 weeks of NT treatment demonstrated a strong correlation of high plasma level to poor antidepressive effect of NT. No correlation could be obtained between side-effects, which were few, and plasma level. The non-proteinbound fraction in plasma was found to 7% (SD 1.83) by simultaneous determinations of NT in plasma and CSF in 13 patients. The variation in the proteinbinding was not likely to invalidate the over all results based on total NT determination. A therapeutic plasma range of 50-150 ng/ml is recommended. PMID:766041

  20. Mirtazapine versus other antidepressive agents for depression

    PubMed Central

    Watanabe, Norio; Omori, Ichiro M; Nakagawa, Atsuo; Cipriani, Andrea; Barbui, Corrado; Churchill, Rachel; Furukawa, Toshi A

    2014-01-01

    Background Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice. Objectives The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis review group’s specialised register (CCDANCTR), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to April 2011), EMBASE, (1980 to July 2011) MEDLINE (1950 to July 2011) and PsycINFO (1974 to July 2011). Reference lists of the reports of relevant studies were checked and experts in the field contacted. The review was not limited to English-language articles. Selection criteria Randomised controlled trials (RCTs) allocating participants with major depression to mirtazapine versus any other antidepressive agent. Data collection and analysis Two authors independently checked eligibility and extracted data on an intention-to-treat basis. The primary outcome was response to treatment. The secondary outcomes included dropouts and individual adverse events. Meta-analyses were conducted using the random-effects model. Main results A total of 29 RCTs (n = 4974), mostly following up the participants for six weeks in outpatient clinics and inadequately reporting the risk of bias, were included. In comparison with tricyclic antidepressants (10 trials, n = 1553) there was no robust evidence to detect a difference between mirtazapine and tricyclics in terms of response at two weeks (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.64 to 1.13) or at the end of acute-phase treatment (at 6 to 12 weeks) (OR 0.89, 95% CI 0.72 to 1.10). In comparison with selective serotonin reuptake inhibitors (SSRIs) (12 trials, n = 2626) mirtazapine was significantly more

  1. Factors associated with antidepressant use in residents with and without dementia in Australian aged care facilities

    PubMed Central

    Hiltunen, Henna; Tan, Edwin C. K.; Ilomäki, Jenni; Hilmer, Sarah N.; Visvanathan, Renuka; Emery, Tina; Robson, Leonie; Jones, Mary J.; Hartikainen, Sirpa; Bell, J. Simon

    2016-01-01

    Objective: Depressive symptoms are highly prevalent in residential aged care facilities (RACFs). The prevalence of antidepressant use is increasing but the effectiveness of antidepressants in people with dementia is uncertain. The objective of the study was to investigate factors associated with antidepressant use in residents with and without dementia. Methods: This was a prospective cross-sectional study of 383 residents in six Australian RACFs. Data on health status, medications and demographics were collected by trained study nurses from April to August 2014. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with antidepressant use. Analyses were stratified by dementia and depression. Results: Overall, 183 (47.8%) residents used antidepressants. The prevalence of antidepressant use was similar among residents with and without dementia. Clinician-observed pain was inversely associated with antidepressant use in the main analysis (AOR = 0.56, 95% CI = 0.32–0.99) and in subanalyses for residents with documented depression (AOR = 0.51, 95% CI = 0.27–0.96). In residents with dementia, moderate quality of life was associated with a lower odds of antidepressant use compared with poor quality of life (AOR = 0.35, 95% C I= 0.13–0.95). In residents without dementia, analgesic use was associated with antidepressant use (AOR = 2.34, 95% CI = 1.07–5.18). Conclusions: The prevalence of antidepressant use was similar in residents with and without dementia. Clinician-observed pain was inversely associated with antidepressant use but there was no association between self-reported pain and antidepressant use. PMID:27298718

  2. Sertraline versus other antidepressive agents for depression

    PubMed Central

    Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

    2014-01-01

    Background The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. Objectives To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either

  3. Venlafaxine: more dangerous than most "selective" serotonergic antidepressants.

    PubMed

    2016-04-01

    Venlafaxine is a serotonergic and noradrenergic antidepressant. It shares the same serotonergic adverse effects as the "selective" serotonin reuptake inhibitor (SSRI) antidepressants while in addition provoking noradrenergic adverse effects, in particular cardiovascular disorders, yet offers no demonstrated advantages over SSRIs in terms of efficacy. Several cohort studies using data from a UK database have shown that venlafaxine overdoses are more frequently fatal than SSRI overdoses. Several meta-analyses of more than 70 published and unpublished randomised clinical trials, including about 7000 patients in total, have shown that treatment discontinuation due to adverse effects is more common with venlafaxine than with SSRI antidepressants. Venlafaxine can provoke dose-dependent blood pressure elevation, sometimes requiring treatment discontinuation. Exposure to venlafaxine during the second and third trimesters of pregnancy increases the risk of pre-eclampsia and eclampsia. A cohort study in about 50 elderly patients and analysis of several hundred reported suicide attempts by venlafaxine overdose demonstrated a risk of QT interval prolongation, which can lead to torsades de pointes, an unusual and potentially fatal type of ventricular tachycardia. Large British and Danish cohort studies found no increased risk of sudden cardiac death with venlafaxine compared with other antidepressants. However, since only 3.5% and 7% of the patients were using venlafaxine, the statistical power of these studies was relatively low. In practice, the data available as of mid-2015 from clinical trials and epidemiological studies confirm the harms foreseeable from venlafaxine's pharmacological properties: a higher risk of cardiovascular adverse effects and of fatal overdoses than with most SSRI antidepressants. Since venlafaxine and SSRI antidepressants have similar and limited efficacy, venlafaxine is best avoided. An SSRI anti-depressant is a more reasonable option, with the

  4. Times to Discontinue Antidepressants Over 6 Months in Patients with Major Depressive Disorder

    PubMed Central

    Jung, Woo-Young; Jang, Sae-Heon; Jae, Young-Myo; Kong, Bo-Geum; Kim, Ho-Chan; Choe, Byeong-Moo; Kim, Jeong-Gee; Kim, Choong-Rak

    2016-01-01

    Objective The aim of the present study was to investigate differences in discontinuation time among antidepressants and total antidepressant discontinuation rate of patients with depression over a 6 month period in a naturalistic treatment setting. Methods We reviewed the medical records of 900 patients with major depressive disorder who were initially prescribed only one kind of antidepressant. The prescribed antidepressants and the reasons for discontinuation were surveyed at baseline and every 4 weeks during the 24 week study. We investigated the discontinuation rate and the mean time to discontinuation among six antidepressants groups. Results Mean and median overall discontinuation times were 13.8 and 12 weeks, respectively. Sertraline and escitalopram had longer discontinuation times than that of fluoxetine, and patients who used sertraline discontinued use significantly later than those taking mirtazapine. No differences in discontinuation rate were observed after 24 weeks among these antidepressants. About 73% of patients discontinued antidepressant treatment after 24 weeks. Conclusion Sertraline and escitalopram tended to have longer mean times to discontinuation, although no difference in discontinuation rate was detected between antidepressants after 24 weeks. About three-quarters of patients discontinued antidepressant maintenance therapy after 24 weeks. PMID:27482246

  5. A role of Yueju in fast-onset antidepressant action on major depressive disorder and serum BDNF expression: a randomly double-blind, fluoxetine-adjunct, placebo-controlled, pilot clinical study

    PubMed Central

    Wu, Ruyan; Zhu, Dandan; Xia, Youchun; Wang, Haosen; Tao, Weiwei; Xue, Wenda; Xia, Baomei; Ren, Li; Zhou, Xin; Li, Guochun; Chen, Gang

    2015-01-01

    Introduction Conventional antidepressants, including fluoxetine, have a major disadvantage in delayed onset of efficacy. Yueju, an herbal medicine used to treat mood disorders was recently found to exhibit rapid antidepressant effects. The present study was conducted to evaluate the role of Yueju in rapidly acting on major depressive disorder (MDD). Methods Participants were MDD patients with scores of 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20 and without history of antidepressant use. They randomly received daily oral doses of Yueju (23 g/day) plus fluoxetine (20 mg/day) (experimental group) or placebo plus fluoxetine (control group) for 7 days. HDRS-24 was used as the primary outcome measurement at baseline, and on days 1, 3, 5, and 7. Concentrations of serum brain-derived neurotrophic factor (BDNF) were assessed at baseline and on days 1 and 7. Results In all, 18 participants met the criteria for data analysis. Compared to baseline level, only experimental group showed significant decrease of HDRS-24 score from day 3 to day 7 (P<0.05). Experimental group also showed significant improvement compared with control group from day 3 to day 7 (P<0.05). No correlation between treatment outcomes with serum BDNF levels was observed. However, experimental group showed significant correlation for serum BDNF level on day 1 with day 7 (r=0.721, P=0.028), whereas the control group did not. Conclusion Yueju likely contributes to fast-onset antidepressant effects on MDD. Further investigation is necessary to firmly establish the ancient formula as a safe, efficacious, and rapidly acting alternative medicine for MDD treatment. PMID:26273204

  6. Semen abnormalities with SSRI antidepressants.

    PubMed

    2015-01-01

    Despite decades of widespread use, the adverse effect profile of "selective" serotonin reuptake inhibitor (SSRI) antidepressants has still not been fully elucidated. Studies in male animals have shown delayed sexual development and reduced fertility. Three prospective cohort studies conducted in over one hundred patients exposed to an SSRI for periods ranging from 5 weeks to 24 months found altered semen param-eters after as little as 3 months of exposure: reduced sperm concentration, reduced sperm motility, a higher percentage of abnormal spermatozoa, and increased levels of sperm DNA fragmentation. One clinical trial showed growth retardation in children considered depressed who were exposed to SSRls. SSRls may have endocrine disrupting properties. Dapoxetine is a short-acting serotonin reuptake inhibitor that is chemically related to fluoxetine and marketed in the European Union for men complaining of premature ejaculation. But the corresponding European summary of product characteristics does not mention any effects on fertility. In practice, based on the data available as of mid-2014, the effects of SSRI exposure on male fertility are unclear. However, it is a risk that should be taken into account and pointed out to male patients who would like to father a child or who are experiencing fertility problems. PMID:25729824

  7. Depression: How to Safely Take Antidepressants

    MedlinePlus

    ... take, including over-the-counter medicines and herbal health products (such as St. John's wort). Ask your doctor and pharmacist if any of your regular medicines can cause problems when combined with an antidepressant. What is antidepressant ...

  8. Antidepressants Not Just for Depression Any More

    MedlinePlus

    ... urinary problems and bulimia. Depression expert Dr. Peter Kramer said antidepressants have a wide range of potential ... these are not necessarily best called antidepressants," said Kramer, a clinical professor emeritus of psychiatry and human ...

  9. Starting antidepressant use: a qualitative synthesis of UK and Australian data

    PubMed Central

    Anderson, Claire; Kirkpatrick, Susan; Ridge, Damien; Kokanovic, Renata; Tanner, Claire

    2015-01-01

    Objective To explore people's experiences of starting antidepressant treatment. Design Qualitative interpretive approach combining thematic analysis with constant comparison. Relevant coding reports from the original studies (generated using NVivo) relating to initial experiences of antidepressants were explored in further detail, focusing on the ways in which participants discussed their experiences of taking or being prescribed an antidepressant for the first time. Participants 108 men and women aged 22–84 who had taken antidepressants for depression. Setting Respondents recruited throughout the UK during 2003–2004 and 2008 and 2012–2013 and in Australia during 2010–2011. Results People expressed a wide range of feelings about initiating antidepressant use. People's attitudes towards starting antidepressant use were shaped by stereotypes and stigmas related to perceived drug dependency and potentially extreme side effects. Anxieties were expressed about starting use, and about how long the antidepressant might begin to take effect, how much it might help or hinder them, and about what to expect in the initial weeks. People worried about the possibility of experiencing adverse effects and implications for their senses of self. Where people felt they had not been given sufficient time during their consultation information or support to take the medicines, the uncertainty could be particularly unsettling and impact on their ongoing views on and use of antidepressants as a viable treatment option. Conclusions Our paper is the first to explore in-depth patient existential concerns about start of antidepressant use using multicountry data. People need additional support when they make decisions about starting antidepressants. Health professionals can use our findings to better understand and explore with patients’ their concerns before their patients start antidepressants. These insights are key to supporting patients, many of whom feel intimidated by the

  10. Human cysticercosis: antigens, antibodies and non-responders.

    PubMed Central

    Flisser, A; Woodhouse, E; Larralde, C

    1980-01-01

    Immunoelectrophoresis of sera from patients with brain cysticercosis against a crude antigenic extract from Cysticercus cellulosae indicates that nearly 50% of the patients do not make sufficient antibodies to ostensively precipitate. The other 50% of the patients who do make precipitating antibodies show a very heterogeneous response in the number of antigens they recognize as well as in the type of antigen--as classified by their electrophoretic mobilities. The most favoured, called antigen B, is recognized by 84% of positive sera and corresponds to one or a limited number of antigens isoelectric at pH 8.6. Indirect immunofluorescence with monospecific anti-human immunoglobulins, performed upon the immunoelectrophoretic preparations, reveal that all cysticercus antigens induced the synthesis of antibodies in the immunoglobulin classes in the order G greater than M greater than E greater than A greater than D. Finally, antigen H (an anodic component) seems to favour IgE relative to its ability to induce IgG. Thus, although in natural infection a good proportion of cysticercotic patients do not seem to mount an energetic antibody response against the parasite, giving rise to some speculations about immunosuppression, the fact that 50% do synthesize antibodies allows for some optimistic expectations from vaccination of humans--in view of the good results of vaccination in experimental animals mediated by IgG antibodies. A likely prospect for a human vaccine would be antigen B because it is the most frequently detected by humans, although its immunizing and toxic properties remain to be properly studied. Images FIG. 1 FIG. 3 FIG. 6 PMID:7389197

  11. Antidepressants and testicular cancer: cause versus association.

    PubMed

    Andrade, Chittaranjan

    2014-03-01

    A data mining study that examined associations between 105 drugs and 55 cancer sites found significant associations between 2 selective serotonin reuptake inhibitors (fluoxetine and paroxetine) and testicular cancer. The study suggested several reasons why these associations merited further investigation. A later study tested specific relationships between 12 antidepressant drugs and testicular cancer and subtypes thereof; whereas significant relationships were again found, these disappeared after adjusting for confounding variables. These 2 studies are educative because they illustrate how false-positive results can easily arise in exploratory research and how confounding may be responsible for statistically significant relationships in study designs that are not randomized controlled trials. PMID:24717391

  12. Non-Responders to Intravenous Immunoglobulin and Coronary Artery Dilatation in Kawasaki Disease: Predictive Parameters in Korean Children

    PubMed Central

    Kim, Bo Young; Kim, Dongwan; Kim, Yong Hyun; Ryoo, Eell; Sun, Yong Han; Jeon, In-sang; Jung, Mi-Jin; Cho, Hye Kyung; Tchah, Hann; Choi, Deok Young

    2016-01-01

    Background and Objectives In Kawasaki disease (KD), high dose intravenous immunoglobulin (IVIG) significantly lowers the coronary complications. However, some patients either do not respond to initial therapy or develop coronary complications. We aimed to identify the predictive factors for unresponsiveness to initial IVIG therapy and coronary artery dilatation (CAD; defined by Z-score≥2.5) in the acute phase and convalescent phase. Subjects and Methods A retrospective review was conducted of 703 patients with KD, admitted to Gachon University Gil Medical Center between January 2005 and June 2013. The patients were divided into two groups—IVIG responders vs. non-responders—based on the IVIG treatments, and presence of fever after treatment. Further, these groups were divided into two subgroups based on their CAD. Results Among the 703 patients with KD, the rate of non-responders to initial IVIG was 16.8%. Serum total bilirubin, platelet count, and neutrophil proportion were independent predictive parameters of unresponsiveness (p<0.05). CAD was found in 234 patients (33.3%) in the acute phase, and in 32 patients (4.6%) in the convalescent phase. Male gender, fever duration, serum C-reactive protein, and white blood cell count were related to CAD (p<0.05). CAD was detected more frequently in non-responders than in the responders (47.5% vs. 31.5%, p=0.001). Kobayashi, Egami, and Sano scoring systems applied to our study population reflected low sensitivities (28.0-33.9%). Conclusion Several independent parameters were related to unresponsiveness to the initial IVIG or CAD. These parameters might be helpful in establishing more focused and careful monitoring of high-risk KD patients in Korea. PMID:27482264

  13. Long-term antidepressant use: patient perspectives of benefits and adverse effects

    PubMed Central

    Cartwright, Claire; Gibson, Kerry; Read, John; Cowan, Ondria; Dehar, Tamsin

    2016-01-01

    Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment. This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue. PMID:27528803

  14. [Prospective evaluation of antidepressant discontinuation].

    PubMed

    Mourad, I; Lejoyeux, M; Adès, J

    1998-01-01

    The authors prospectively assessed symptoms induced by the interruption of antidepressants in 16 patients (11 women and 5 men), aged from 33 to 85 years (mean = 52.4 +/- 16.4), treated with antidepressants since at least two weeks. All patients were free of alcohol abuse or dependence disorder and of other dependence to psychoactive substances. None of them presented medical illness. Diagnosis were made by separate evaluations by two authors and confirmed with a semistructered assessment instrument: the Schedule for Affective Disorders and Schizophrenia (Lifetime Version). All patients were submitted to a brutal discontinuation of their antidepressant agent. Patients were assessed twice, before the interruption of the antidepressant, and 72 hours later. Effects of antidepressant interruption were assessed by several means. Modification of anxiety and depression were evaluated using the Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale. Symptoms of withdrawal were assessed with Cassano and al.'s scale SESSH including an evaluation of anxiety, agitation, irritability, anergy, difficulty on concentrating, depersonalization, sleep and appetite disorders, muscle pains, nausea, tremor, sweating, altered taste, hyperosmia, paresthesias, photophobia, motor incoordination, dizziness, hyperacousia pain, delirium. Fourteen of the 16 patients (87.5%) presented modifications of their somatic or psychic state 3 days after the interruption of the antidepressant treatment. Most frequent symptoms were: increase in anxiety (31%), increase in irritability (25%), sleep disorders (19%), decrease of anergia and fatigue (19%). Mean scores of anxiety and depression were not significantly modified by the withdrawal. Following TCAs interruption (7 patients) most frequent symptoms were sleep disorders; increase in anxiety, nausea. Among patients withdrawn from SSRIs (6 patients), most frequent symptoms were increase in anxiety, increase in irritability

  15. Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

    PubMed

    Yu, Jing-Jie; Pei, Liu-Bao; Zhang, Yong; Wen, Zi-Yu; Yang, Jian-Li

    2015-08-01

    Major depressive disorder is a devastating mental illness leading to a lifetime prevalence of higher than 16% on individuals. The treatment delay and inevitable adverse effects are major limitations of current depression interventions. Emerging evidence indicates that curcumin produced significant antidepressant properties in depression in both rodents and humans without adverse effects. Therefore, it is necessary to further clarify the antidepressant actions of curcumin and the underlying mechanism in depressed patients. A total of 108 male adults aged between 31 and 59 years were systematically recruited in Tianjin Anding Hospital. Subjects were administered the Chinese version of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale that measures different scores of depressive symptoms. The subjects were asked to take 2 capsules containing either 1000 mg of curcumin or placebo soybean powder daily for 6 weeks on the basis of their current antidepressant medications. The plasma levels of interleukin 1β, tumor necrosis factor α, brain-derived neurotrophic factor, and salivary cortisol were measured by enzyme-linked immunosorbent assay before and after curcumin or placebo treatment during the 6-week procedure. Chronic supplementation with curcumin produced significant antidepressant behavioral response in depressed patients by reduction of 17-item Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale scores. Furthermore, curcumin decreases inflammatory cytokines interleukin 1β and tumor necrosis factor α level, increases plasma brain-derived neurotrophic factor levels, and decreases salivary cortisol concentrations compared with placebo group. These findings indicate the potential benefits of further implications of supplementary administration of curcumin to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder. PMID:26066335

  16. Breast cancer recurrence in relation to antidepressant use

    PubMed Central

    Chubak, Jessica; Bowles, Erin J.A.; Yu, Onchee; Buist, Diana S.M.; Fujii, Monica; Boudreau, Denise M.

    2016-01-01

    Purpose Women with breast cancer frequently use antidepressants; however, questions about the effect of these medications on breast cancer recurrence remain. Methods We identified 4216 women ≥18 years with an incident stage I or II breast cancer diagnosed between 1990–2008 in a mixed model healthcare delivery system linked to a cancer registry. Recurrences were ascertained from chart review. Medication exposures were extracted from electronic pharmacy records. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) to assess the association between antidepressant use and breast cancer recurrence and mortality. We also conducted analyses restricted to tamoxifen users. Results Antidepressants overall, tricyclic antidepressants, and selective serotonin reuptake inhibitors were not associated with risk of breast cancer recurrence or mortality. Women taking paroxetine only (adjusted HR: 1.66; 95% CI: 1.02, 2.71) and trazadone only (adjusted HR: 1.76; 95% CI: 1.06, 2.92), but not fluoxetine only (adjusted HR: 0.92; 95% CI: 0.55, 1.53), had higher recurrence risks than antidepressant non-users. There was some suggestion of an increased recurrence risk with concurrent paroxetine and tamoxifen use compared to users of tamoxifen only (adjusted HR: 1.49; 95% CI: 0.79, 2.83). Conclusions In general, antidepressants did not appear increase risk of breast cancer recurrence; though there were some suggested increases in risk that warrant further investigation in other datasets. Our results combined systematically and quantitatively with results from other studies may be useful for patients and providers making decisions about antidepressant use after breast cancer diagnosis. PMID:26518198

  17. Treatment response in relation to subthreshold bipolarity in patients with major depressive disorder receiving antidepressant monotherapy: a post hoc data analysis (KOMDD study)

    PubMed Central

    Park, Young-Min; Lee, Bun-Hee

    2016-01-01

    Background The aim of this observational study was to determine whether subthreshold bipolarity affects treatment response and remission in patients with major depressive disorder receiving antidepressant (AD) monotherapy over a 6-month follow-up period. Methods Seventy-eight patients with major depressive disorder were stratified into two subgroups according to the presence of subthreshold bipolarity, identified using the Korean version of the Mood Disorder Questionnaire (K-MDQ), which classifies patients as positive for a screening of bipolarity based on the cutoff for the total K-MDQ score (ie, 7 points). They received AD monotherapy such as escitalopram, sertraline, paroxetine, or tianeptine for 6 months. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale, and Beck Scale for Suicide Ideation were applied at baseline, 1 week, 3 weeks, 2 months, 3 months, and 6 months. Results The mean HAMD, BDI, and Beck Scale for Suicide Ideation scores were higher in the bipolarity group than in the nonbipolarity group at 3 weeks. The mean BDI score was also higher in the bipolarity group than in the nonbipolarity group at 6 months. Evaluation of the ratio of improvement for each scale revealed different patterns of percentage changes between the two groups over the 6-month follow-up period. Furthermore, the response and remission rates (as assessed using BDI and HAMD scores) were higher in the nonbipolarity group than in the bipolarity group, with the exception of HAMD scores at the 3-week follow-up time point. Conclusion The findings of this study showed that depressed patients with bipolarity had a worse response to AD monotherapy than did those without bipolarity. PMID:27274258

  18. Depressive symptoms, antidepressant medication use and new onset of diabetes in participants of the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study

    PubMed Central

    Marrero, David G.; Ma, Yong; de Groot, Mary; Horton, Edward S.; Price, David W.; Barrett-Connor, Elizabeth; Carnethon, Mercedes R.; Knowler, William C.

    2015-01-01

    Objective To assess in participants in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study (DPP/DPPOS) whether diagnosis of diabetes predicted: elevated depressive symptoms (DS) or antidepressant medicine (ADM) use after diagnosis; diabetes status or duration had significant effect on DS or ADM use; and associations between A1C, fasting plasma glucose (FPG), normalization of FPG and DS or ADM use post diagnosis. Methods DPP participants in 3 treatment arms [intensive lifestyle (ILS), metformin (MET), placebo (PLC)] were assessed semiannually or annually for diabetes, glucose control, ADM use, and DS. DS was measured using Beck Depression Inventory (BDI) questionnaire. Among the total 3234 enrolled participants, 1285 developed diabetes whose levels of depression were measured before and after their diabetes diagnosis. Results Neither DS nor ADM use increased significantly following diabetes diagnosis. After diabetes diagnosis, higher FPG was associated with greater ADM use in the ILS arm independent of potential confounders; a 10 mg/dl higher in FPG is associated with 8.8% more odds of ADM use. Higher FPG, and higher A1C were associated with higher BDI scores in all three arms. On average, a participant with 10 mg/dl higher rise in FPG had a 0.07 increase in BDI score. Similarly, 1% higher A1c was associated with a 0.21 point increase in BDI score. On contrary, normalization of FPG was associated with lower BDI scores. In participants with FPG that had normalized, there was a decrease of 0.30 points in the BDI score compared to those whose FPG had not normalized. Conclusions Contrary to clinical attributions, the diagnosis of diabetes did not show an immediate impact on BDI scores or ADM use. However, higher glucose levels after diagnosis were associated with small but significant higher BDI score and more ADM use. PMID:25775165

  19. The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment.

    PubMed

    Saveanu, Radu; Etkin, Amit; Duchemin, Anne-Marie; Goldstein-Piekarski, Andrea; Gyurak, Anett; Debattista, Charles; Schatzberg, Alan F; Sood, Satish; Day, Claire V A; Palmer, Donna M; Rekshan, William R; Gordon, Evian; Rush, A John; Williams, Leanne M

    2015-02-01

    We aimed to characterize a large international cohort of outpatients with MDD within a practical trial design, in order to identify clinically useful predictors of outcomes with three common antidepressant medications in acute-phase treatment of major depressive disorder (MDD). The international Study to Predict Optimized Treatment in Depression has presently enrolled 1008 treatment-seeking outpatients (18-65 years old) at 17 sites (five countries). At pre-treatment, we characterized participants by symptoms, clinical history, functional status and comorbidity. Participants were randomized to receive escitalopram, sertraline or venlafaxine-extended release and managed by their physician following usual treatment practices. Symptoms, function, quality of life, and side-effect outcomes were assessed 8 weeks later. The relationship of anxiety to response and remission was assessed by comorbid Axis I diagnosis, presence/absence of anxiety symptoms, and dimensionally by anxiety symptom severity. The sample had moderate-to-severe symptoms, but substantial comorbidity and functional impairment. Of completers at week 8, 62.2% responded and 45.4% reached remission on the 17-item Hamilton Rating Scale for Depression; 53.3% and 37.6%, respectively on the 16-item Quick Inventory of Depressive Symptoms. Functional improvements were seen across all domains. Most participants had side effects that occurred with a frequency of 25% or less and were reported as being in the "none" to minimal/mild range for intensity and burden. Outcomes did not differ across medication groups. More severe anxiety symptoms at pre-treatment were associated with lower remission rates across all medications, independent of depressive severity, diagnostic comorbidity or side effects. Across medications, we found consistent and similar improvements in symptoms and function, and a dimensional prognostic effect of comorbid anxiety symptoms. These equivalent outcomes across treatments lay the foundation for

  20. The effects of tricyclic antidepressants on breast cancer risk.

    PubMed

    Sharpe, C R; Collet, J-P; Belzile, E; Hanley, J A; Boivin, J-F

    2002-01-01

    To test the hypothesis that tricyclic antidepressant use increases invasive female breast cancer incidence, we carried out a case-control study within the population of female beneficiaries of the Saskatchewan Prescription Drug Plan aged 35 years from 1981-995 with no history of cancer since 1970. This agency has provided full or partial coverage for outpatient prescriptions to Saskatchewan residents since 1975. We accrued 5882 histologically proven cases and 23,517 controls, randomly selected from the source population and individually matched on age and sampling time. Heavy exposure to any tricyclic antidepressants was associated with an elevated rate ratio for breast cancer 11-15 years later (2.02, 95% confidence interval: 1.34-3.04). Post hoc analyses based on the results of genotoxicity studies carried out using Drosophila melanogaster suggested that the increased risk could be attributed to the use of the six genotoxic tricyclic antidepressants, and not to the use of the four nongenotoxic tricyclic antidepressants. However, our results may have been confounded by the effects of other determinants of breast cancer associated with tricyclic antidepressant use. PMID:11857018

  1. The effects of tricyclic antidepressants on breast cancer risk

    PubMed Central

    Sharpe, C R; Collet, J-P; Belzile, E; Hanley, J A; Boivin, J-F

    2002-01-01

    To test the hypothesis that tricyclic antidepressant use increases invasive female breast cancer incidence, we carried out a case–control study within the population of female beneficiaries of the Saskatchewan Prescription Drug Plan aged ⩾35 years from 1981–1995 with no history of cancer since 1970. This agency has provided full or partial coverage for outpatient prescriptions to Saskatchewan residents since 1975. We accrued 5882 histologically proven cases and 23 517 controls, randomly selected from the source population and individually matched on age and sampling time. Heavy exposure to any tricyclic antidepressants was associated with an elevated rate ratio for breast cancer 11–15 years later (2.02, 95% confidence interval: 1.34–3.04). Post hoc analyses based on the results of genotoxicity studies carried out using Drosophila melanogaster suggested that the increased risk could be attributed to the use of the six genotoxic tricyclic antidepressants, and not to the use of the four nongenotoxic tricyclic antidepressants. However, our results may have been confounded by the effects of other determinants of breast cancer associated with tricyclic antidepressant use. British Journal of Cancer (2002) 86, 92–97. DOI: 10.1038/sj/bjc/6600013 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11857018

  2. Glutamate system as target for development of novel antidepressants.

    PubMed

    Catena-Dell'Osso, Mario; Fagiolini, Andrea; Rotella, Francesco; Baroni, Stefano; Marazziti, Donatella

    2013-08-01

    Depression is a common psychiatric condition characterized by affective, cognitive, psychomotor, and neurovegetative symptoms that interfere with a person's ability to work, study, deal with interpersonal relationships, and enjoy once-pleasurable activities. After the serendipitous discovery of the first antidepressants, for years the only pharmacodynamic mechanisms explored in the search of novel antidepressants were those related to the 3 main monoamines: serotonin, norepinephrine, and dopamine. New-generation monoaminergic antidepressants, such as selective-serotonin and dual-acting serotonin/norepinephrine reuptake inhibitors, improved treatment and quality of life of depressed patients. Nevertheless, there are still important clinical limitations: the long latency of onset of the antidepressant action; side effects, which can lead to early discontinuation; low rate of response; and high rate of relapse/recurrence. Therefore, in the last several years, the focus of research has moved from monoamines toward other molecular mechanisms, including glutamatergic (Glu) neurotransmission. This review provides a comprehensive overview of the current knowledge on the Glu system and on its relationships with mood disorders. Up to now, N-methyl-D-aspartate (NMDA) receptor antagonists, in particular ketamine, provided the most promising results in preclinical studies and produced a consistent and rapid, although transient, antidepressant effect with a good tolerability profile in humans. Although data are encouraging, more double-blind, randomized, placebo-controlled trials are needed to clarify the real potentiality of ketamine, and of the other Glu modulators, in the treatment of unipolar and bipolar depression. PMID:23369807

  3. Antidepressant adherence after psychiatric hospitalization

    PubMed Central

    Zivin, Kara; Ganoczy, Dara; Pfeiffer, Paul N.; Miller, Erin M.; Valenstein, Marcia

    2010-01-01

    Objective Depressed patients discharged from psychiatric hospitalizations face increased risks for adverse outcomes including suicide, yet antidepressant adherence rates during this high-risk period are unknown. Using Veterans Affairs (VA) data, we assessed antidepressant adherence and predictors of poor adherence among depressed veterans following psychiatric hospitalization. Method We identified VA patients nationwide with depressive disorders who had a psychiatric hospitalization between April 1, 1999 and September 30, 2003, received antidepressant medication, and had an outpatient appointment following discharge. We calculated medication possession ratios (MPRs), a measure of medication adherence, within three and six months following discharge. We assessed patient factors associated with having lower levels of adherence (MPRs <0.8) after discharge. Results 20,931 and 23,182 patients met criteria for three and six month MPRs. The mean three month MPR was 0.79 (s.d.=0.37). The mean six month MPR was 0.66 (s.d.=0.40). Patients with poorer adherence were male, younger, non-white, and had a substance abuse disorder, but were less likely to have PTSD or other anxiety disorders. Conclusion Poor antidepressant adherence is common among depressed patients after psychiatric hospitalization. Efforts to improve adherence at this time may be critical in improving the outcomes of these high-risk patients. PMID:19609666

  4. [Switching and combining strategies of antidepressant medications].

    PubMed

    Charpeaud, Thomas; Moliere, Fanny; Bubrovszky, Maxime; Haesebaert, Frédéric; Allaïli, Najib; Bation, Rémy; Nieto, Isabel; Richieri, Raphaëlle; Saba, Ghassen; Bellivier, Frank; Bennabi, Djamila; Holtzmann, Jérôme; Camus, Vincent; Courtet, Philippe; Courvoisier, Pierre; d'Amato, Thierry; Doumy, Olivier; Garnier, Marion; Bougerol, Thierry; Lançon, Christophe; Haffen, Emmanuel; Leboyer, Marion; Llorca, Pierre-Michel; Vaiva, Guillaume; El-Hage, Wissam; Aouizerate, Bruno

    2016-03-01

    Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects. PMID:26995511

  5. National Estimates of Antidepressant Medication Use among U.S. Children, 1997-2002

    ERIC Educational Resources Information Center

    Vitiello, Benedetto; Zuvekas, Samuel H.; Norquist, Grayson S.

    2006-01-01

    Objective: A threefold increase in the use of antidepressants has been reported among children (18 years old and younger) between 1987 (0.3%) and 1996 (1.0%). The aim of this study was to determine whether pediatric use of antidepressants continued to rise at a national level during the period 1997-2002. Method: The Medical Expenditure Panel…

  6. Antidepressants and Youth Suicide in New York City, 1999-2002

    ERIC Educational Resources Information Center

    Leon, Andrew C.; Marzuk, Peter M.; Tardiff, Kenneth; Bucciarelli, Angela; Piper, Tinka Markham; Galea, Sandro

    2006-01-01

    Objective: To determine the proportion of youth suicides in New York City from 1999 to 2002 in which antidepressants were detected at autopsy. Method: This is a medical examiner surveillance study of suicides in New York City among those younger than 18 years of age. The outcome measure is serum toxicology for antidepressants. Results: From 1999…

  7. [Critical evaluation of the use of antidepressives in childhood].

    PubMed

    Conde López, V J; Ballesteros Alcalde, M C; Franco Martín, M A; Geijo Uribe, M S

    1997-01-01

    In the introduction the authors study some technical, methodological, ethical, administrative and marketing problems about the evaluation and investigation in child and adolescence psychopharmacology. They make a revision and critical evaluation about. As a whole the clinic use of antidepressive drugs in childhood psychiatry. Then, some open and controlled trial about tricyclic antidepressives are evaluated. After this, the authors present the most important advances about the open and controlled clinic trials with several antidepressives: tricyclic, tetracyclic, ISSR and MAO-Inhibitors and other drugs (placebo response, psychotherapy, imipramine, nortryptiline, amitriptyline, fluoxetine, MAO-Inhibitors, lithium, mianserin, maprotyline, etc.). Beside, placebo effect, response prediction factors, biologic markers, diagnostic criteria, evaluation methods and technics, drugs associations, clinic types of child depression, etc, are studied. In the last, the authors present some clinical conclusions about this subject. PMID:9245188

  8. Antidepressant Activity of Methanolic Extract of Amaranthus Spinosus

    PubMed Central

    Ashok Kumar, B.S; Lakshman, K; Velmurugan, C; Sridhar, S.M; Gopisetty, Saran

    2014-01-01

    Introduction Depressive disorder is a prevalent psychiatric disorder, which affects 21% of the world population. The presently using drugs can impose a variety of side-effects including cardiac toxicity, hypopiesia, sexual dysfunction, body weight gain, and sleep disorder. During the last decade, there is a growing interest in the therapeutic effects of natural products on mental disorders. Amaranthus spinosus was investigation for antidepressant activity. Methods Antidepressant activity of methanolic extract of Amaranthus spinosus (MEAS) was investigated by using Forced swimming test (FST) and Tail suspension test (TST) models. Escitalopram and Imipramine were used as reference standards. Results It has been observed from our study that both the MEAS at higher concentration showed significant (p<0.01) reduction in immobility in tail suspension and forced swim model of depression comparable to Escitalopram and Imipramine. Discussion However further study is needed to understand mechanism of action and to identify active component responsible for antidepressant like activity. PMID:25436078

  9. Depression, Antidepressants and Bone Health in Older Adults: A Systematic Review

    PubMed Central

    Gebara, Marie Anne; Shea, Marcie L.O.; Lipsey, Kim L; Teitelbaum, Steven L.; Civitelli, Roberto; Müller, Daniel J.; Reynolds, Charles F.; Mulsant, Benoit H.; Lenze, Eric J.

    2014-01-01

    Objectives Some studies have reportedan association between depression or serotonin reuptake inhibitor (SRI) antidepressant use and osteoporosis. This association raises concern about the widespread use of antidepressants in older adults and suggests the need to reevaluate this practice. This review examines the association of both depression and antidepressant use with bone health in older adults and the implications for treatment. Design A systematic review of studies of the association between depression or antidepressants and bone health in older adults. Setting All studies that measured depression or antidepressant exposure and bone mineral density (BMD). Participants Adults aged 60 and above. Measurements Age, site of BMD measurement by dual-energy x-ray absorptiometry (DXA), measure of depression or depressive symptoms, association between BMD changes and depression or antidepressant use. Results Nineteen observational studies met the final inclusion criteria; no experimental studies were found. Several cross-sectional and longitudinal studies found that depression or depressive symptoms were associated with decreased BMD. Few studies and only two longitudinal studies addressed the association between SRI antidepressant use and a decrease in BMD and they had conflicting results. Conclusion Depression and depressive symptoms are associated with decreased bone mass and accelerated bone loss in older adults; putative mechanisms underlying this relationship are discussed. There is insufficient evidence that SRI antidepressants adversely affect bone health.Thus, a change in current recommendations for the use of antidepressants in older adults is not justified at the present time. Given the high public health significance of this question, more studies are required to determine whether (and in whom) antidepressants may be deleterious for bone health. PMID:25039259

  10. Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

    PubMed

    Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

    2014-10-01

    We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014. PMID:25174836

  11. Controversies about the use of antidepressants in pregnancy.

    PubMed

    Robinson, Gail Erlick

    2015-03-01

    There is controversy about the use of antidepressant medication during pregnancy. Decisions about their use are affected by understanding the risks of these medications causing pregnancy loss, congenital malformations, neonatal adaptation syndrome, persistent pulmonary hypertension of the newborn, autism spectrum disorder, or long-term neurocognitive deficits. Although some research has raised concerns about antidepressants causing harm to the fetus and neonate, other studies have disputed these findings or noted that any risks found do not exceed the risk of congenital problems found in 1% to 3% of neonates in the general population. Untreated depression during pregnancy can also cause harm from poor diet, substance abuse, suicidal behavior, or prematurity. Decisions about the use of antidepressants during pregnancy must be based on a risk-benefit analysis based on the best evidence of the risks of treating or not treating maternal depression. PMID:25714252

  12. Trimipramine: a challenge to current concepts on antidepressives.

    PubMed

    Berger, M; Gastpar, M

    1996-01-01

    Although it is chemically a classical tricyclic antidepressant agent, trimipramine shows atypical pharmacological properties. Its well-documented antidepressant action cannot be explained by noradrenaline or serotonin reuptake inhibition or by a down-regulation of beta-adrenoceptors. Furthermore, its receptor affinity profile resembles more that of clozapine, a neuroleptic drug, than that of tricyclic antidepressants. Trimipramine does not reduce, but rather increases, rapid eye movement sleep. It stimulates nocturnal prolactin secretion and inhibits nocturnal cortisol secretion and may act at the level of the hypothalamus on corticotropin-releasing hormone secretion. Trimipramine is of particular value in depressed patients with insomnia, and it has been shown to be effective in the therapy of primary insomnia. As the pharmacological profile indicates, and an open clinical study has shown, trimipramine might also be active as an antipsychotic. The drug is both a tool for increasing our understanding of depression and a potential therapy for several psychiatric disorders. PMID:8863001

  13. Parasomnias and Antidepressant Therapy: A Review of the Literature

    PubMed Central

    Kierlin, Lara; Littner, Michael R.

    2011-01-01

    There exists a varying level of evidence linking the use of antidepressant medication to the parasomnias, ranging from larger, more comprehensive studies in the area of REM sleep behavior disorder to primarily case reports in the NREM parasomnias. As such, practice guidelines are lacking regarding specific direction to the clinician who may be faced with a patient who has developed a parasomnia that appears to be temporally related to use of an antidepressant. In general, knowledge of the mechanisms of action of the medications, particularly with regard to the impact on sleep architecture, can provide some guidance. There is a potential for selective serotonin reuptake inhibitors, tricyclic antidepressants, and serotonin–norepinephrine reuptake inhibitors to suppress REM, as well as the anticholinergic properties of the individual drugs to further disturb normal sleep architecture. PMID:22180745

  14. Early life stress impacts dorsolateral prefrontal cortex functional connectivity in healthy adults: informing future studies of antidepressant treatments

    PubMed Central

    Philip, Noah S.; Valentine, Thomas R.; Sweet, Lawrence H.; Tyrka, Audrey R.; Price, Lawrence H.; Carpenter, Linda L.

    2014-01-01

    Exposure to early life stress (ELS) is strongly associated with poor treatment outcomes, particularly for trauma-associated disorders such as depression. Little research to date, however, has examined the potential effects of ELS on outcomes with newer treatments, such as repetitive transcranial magnetic stimulation (rTMS). This study evaluated whether ELS exposure impacts resting state functional connectivity associated with brain regions targeted by rTMS. Twenty-seven medication-free adults without psychiatric or medical illness (14 with a history of at least moderate ELS) were scanned using a 3T magnetic resonance imaging (MRI) scanner during two 4-minute rest periods. The primary targets of rTMS, the left and right dorsolateral prefrontal cortex (DLPFC), were utilized as seed regions in connectivity analyses. Relative to controls, when seeding the left DLPFC, ELS subjects demonstrated significantly increased local connectivity with the left middle frontal gyrus and negative connectivity with the left precuneus. ELS status was also associated with negative connectivity from the right DLPFC to the left precuneus and left inferior parietal lobule. These findings demonstrate greater dissociation between the executive and default mode networks in individuals with a history of ELS, and these results may inform neuroimaging assessments in future rTMS studies of ELS-related conditions. PMID:24513500

  15. Multimodal antidepressant vortioxetine increases frontal cortical oscillations unlike escitalopram and duloxetine – a quantitative EEG study in rats

    PubMed Central

    Leiser, S C; Pehrson, A L; Robichaud, P J; Sanchez, C

    2014-01-01

    Background and Purpose EEG studies show that 5-HT is involved in regulation of sleep–wake state and modulates cortical oscillations. Vortioxetine is a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, 5-HT1B partial agonist, 5-HT1A agonist, and 5-HT transporter inhibitor. Preclinical (animal) and clinical studies with vortioxetine show positive impact on cognitive metrics involving cortical function. Here we assess vortioxetine's effect on cortical neuronal oscillations in actively awake rats. Experimental Approach Telemetric EEG recordings were obtained with the following treatments (mg·kg−1, s.c.): vehicle, vortioxetine (0.1, 1.0, 3.0, 10), 5-HT1A agonist flesinoxan (2.5), 5-HT3 antagonist ondansetron (0.30), 5-HT7 antagonist SB-269970-A (10), escitalopram (2.0), duloxetine (10) and vortioxetine plus flesinoxan. Target occupancies were determined by ex vivo autoradiography. Key Results Vortioxetine dose-dependently increased wakefulness. Flesinoxan, duloxetine, ondansetron, but not escitalopram or SB-269970-A increased wakefulness. Quantitative spectral analyses showed vortioxetine alone and with flesinoxan increased θ (4–8 Hz), α (8–12 Hz) and γ (30–50 Hz) power. Duloxetine had no effect on θ and γ, but decreased α power, while escitalopram produced no changes. Ondansetron and SB-269970 (≈31–35% occupancy) increased θ power. Flesinoxan (≈41% occupancy) increased θ and γ power. Conclusions and Implications Vortioxetine increased wakefulness and increased frontal cortical activity, most likely because of its 5-HT7 and 5-HT3 antagonism and 5-HT1A agonism. Vortioxetine differs from escitalopram and duloxetine by increasing cortical θ, α and γ oscillations. These preclinical findings suggest a role of vortioxetine in modulating cortical circuits known to be recruited during cognitive behaviours and warrant further investigation as to their clinical impact. PMID:24846338

  16. Preventing relapse in recurrent depression using mindfulness-based cognitive therapy, antidepressant medication or the combination: trial design and protocol of the MOMENT study

    PubMed Central

    2012-01-01

    Background Depression is a common psychiatric disorder characterized by a high rate of relapse and recurrence. The most commonly used strategy to prevent relapse/recurrence is maintenance treatment with antidepressant medication (mADM). Recently, it has been shown that Mindfulness-Based Cognitive Therapy (MBCT) is at least as effective as mADM in reducing the relapse/recurrence risk. However, it is not yet known whether combination treatment of MBCT and mADM is more effective than either of these treatments alone. Given the fact that most patients have a preference for either mADM or for MBCT, the aim of the present study is to answer the following questions. First, what is the effectiveness of MBCT in addition to mADM? Second, how large is the risk of relapse/recurrence in patients withdrawing from mADM after participating in MBCT, compared to those who continue to use mADM after MBCT? Methods/design Two parallel-group, multi-center randomized controlled trials are conducted. Adult patients with a history of depression (3 or more episodes), currently either in full or partial remission and currently treated with mADM (6 months or longer) are recruited. In the first trial, we compare mADM on its own with mADM plus MBCT. In the second trial, we compare MBCT on its own, including tapering of mADM, with mADM plus MBCT. Follow-up assessments are administered at 3-month intervals for 15 months. Primary outcome is relapse/recurrence. Secondary outcomes are time to, duration and severity of relapse/recurrence, quality of life, personality, several process variables, and incremental cost-effectiveness ratio. Discussion Taking into account patient preferences, this study will provide information about a) the clinical and cost-effectiveness of mADM only compared with mADM plus MBCT, in patients with a preference for mADM, and b) the clinical and cost-effectiveness of withdrawing from mADM after MBCT, compared with mADM plus MBCT, in patients with a preference for MBCT

  17. Isolation and identification of the photodegradation products of the photosensitizing antidepressant drug clomipramine. Phototoxicity studies on erythrocytes.

    PubMed

    Canudas, N; Contreras, C

    2002-06-01

    The isolation and identification of the photodegradation products of clomipramine (CIP) in phosphate buffered saline (PBS pH 7.4 and 6.0) solution and methanol under aerobic conditions were studied. Six compounds were identified and four of them were isolated and characterized by spectroscopic methods. A radical mechanism with the participation of the solvent is proposed for the photodegradation of CIP which undergoes homolytic cleavage of the carbon-chlorine bond and also photooxidation of the amine group. CIP was able to induce photohemolysis when it was irradiated in PBS pH 7.4 and in PBS pH 6.0 containing a suspension of human red blood cells (RBCs). The photohemolysis experiments in the presence of additives DABCO and GSH showed nearly total inhibition of drug-induced photohemolysis. The efficient inhibition of photohemolysis by the radical scavenger GSH compared with the inhibition show by DABCO suggests a moderate effect by singlet oxygen. Clomipramine-N-oxide was the unique photoproduct able to induce hemolysis and photohemolysis when it was incubated and irradiated with RBCs for 1 h. A mechanism involving singlet oxygen, radicals and photoproducts is suggested for the reported phototoxicity. PMID:12116878

  18. Cysteamine-related agents could be potential antidepressants through increasing central BDNF levels.

    PubMed

    Tsai, Shih-Jen

    2006-01-01

    Major depressive disorder (MDD) is a common mental disease, but with an unknown etiology. Antidepressants are the main biological treatment for MDD. However, current antidepressive agents have a slow onset of effect and a substantial proportion of MDD patients do not clinically improve, despite maximal medication. Thus, the exploration for new antidepressants with novel strategies may help to develop faster and more effective antidepressant agents. Studies in the recent decades have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and activating the BDNF-signaling pathway may play an important role in their therapeutic mechanism. Cysteamine is a natural product of cells and constitutes the terminal region of the CoA molecule. Recent work has found that cysteamine and a related agent, cystamine, have neuroprotective effects in Huntington's disease (HD) mice, through enhancing central BDNF levels. Furthermore, cystamine or cysteamine injection could increase serum BDNF levels in wild-type mice as well as HD mice. Since activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, cystamine or its derivatives could have potential antidepressant therapeutic effects. Among these agents, pantethine may be one of the most promising agents. It is a naturally occurring compound which can be administered orally with negligible side effects, and is metabolized to cysteamine. Further evaluation of the therapeutic and toxic effects of these cysteamine-related antidepressant agents in MDD animal models is needed before any clinical application. PMID:16797865

  19. Tick-borne encephalitis (TBE) and hepatitis B nonresponders feature different immunologic mechanisms in response to TBE and influenza vaccination with involvement of regulatory T and B cells and IL-10.

    PubMed

    Garner-Spitzer, Erika; Wagner, Angelika; Paulke-Korinek, Maria; Kollaritsch, Herwig; Heinz, Franz X; Redlberger-Fritz, Monika; Stiasny, Karin; Fischer, Gottfried F; Kundi, Michael; Wiedermann, Ursula

    2013-09-01

    Low responsiveness/nonresponsiveness is characterized by an insufficient immune response upon primary and/or booster vaccination and affects 1-10% of vaccinees. In the current study, we aimed to investigate whether nonresponsiveness is an Ag/vaccine-specific phenomenon and to clarify underlying immunological mechanisms. Nonresponders to tick-borne encephalitis (TBE) or hepatitis B Ag with a history of previous TBE vaccinations were booster vaccinated with TBE and influenza vaccine and compared with TBE high responders in terms of humoral and cellular immune response. Postboosters in TBE high responder existing TBE titers increased, and solid humoral responses to influenza vaccine were induced. In TBE nonresponders, low to undetectable prevaccination TBE titers remained low, whereas sufficient influenza Abs were induced. In both TBE groups, a positive correlation of humoral and cellular immune response was seen as high/low TBE titers were associated with sufficient/lack of Ag-specific T cell proliferation. Furthermore, responses to influenza were robust in terms of Abs and cytokine production. In contrast, in hepatitis B nonresponders, sufficient humoral responses to TBE and influenza Ags were induced despite lacking specific IL-2 and IFN-γ production. Importantly, these patients showed high IL-10 baseline levels in vitro. HLA-DR subtypes associated with hepatitis B nonresponsiveness were overrepresented in this group, and high IL-10 levels were linked to these subtypes. Whereas TBE and hepatitis B nonresponders had increased IL-10-producing FOXP3(+) T regulatory cells upon vaccination, only in hepatitis B nonresponders, showing elevated prevaccination IL-10 levels, a prominent population of B regulatory cells was detected. We conclude that immunological pathways of nonresponsiveness follow different patterns depending both on vaccine Ag and genetic predisposition of the vaccinee. PMID:23872054

  20. EMSAM (deprenyl patch): how a promising antidepressant was underutilized.

    PubMed

    Asnis, Gregory M; Henderson, Margaret A

    2014-01-01

    The EMSAM patch is a unique monoamine oxidase inhibitor (MAOI) being the only antidepressant utilizing a transdermal delivery system. This was welcomed by clinicians who hoped that EMSAM would be better tolerated than oral MAOIs and non-MAOI antidepressants, as well as being effective for treatment in a wide spectrum of depressed patients including atypical depression, bipolar depression, and refractory depression. Unfortunately, the clinical use of EMSAM has been underutilized and its potential usefulness overlooked. This article suggests that fear of possible side effects, particularly the "cheese reaction" and serotonin syndrome, are some of the main contributors to underutilization by clinicians. These risks have been significantly exaggerated with the 6 mg/day dose not even requiring a special diet. Other contributing factors leading to underutilization are reviewed such as: the lack of studies addressing many important clinical questions; inadequate data analyses; not evaluating the effect of EMSAM on comorbid psychiatric conditions, particularly anxiety disorders; lack of antidepressant comparators versus EMSAM; no dose-response relationship examined; various depressive subtypes and conditions are unexplored, eg, bipolar depression and refractory depression; poor insurance coverage for an expensive medication; as well as minimal marketing efforts and postmarketing studies. On the other hand, many potential advantages of EMSAM are not highlighted enough in the literature and by pharmaceutical companies which might have increased clinical interest and utilization of the antidepressant. For example, the advantages of EMSAM include: avoidance of swallowing issues, as can be seen with oral antidepressants; minimal side effects, probably due to a favorable pharmacokinetic profile; minimal evidence of suicidal behavior, probably relating to the transdermal route of administration; low rates of inducing hypomanic/manic episodes; as well as significant efficacy in

  1. EMSAM (deprenyl patch): how a promising antidepressant was underutilized

    PubMed Central

    Asnis, Gregory M; Henderson, Margaret A

    2014-01-01

    The EMSAM patch is a unique monoamine oxidase inhibitor (MAOI) being the only antidepressant utilizing a transdermal delivery system. This was welcomed by clinicians who hoped that EMSAM would be better tolerated than oral MAOIs and non-MAOI antidepressants, as well as being effective for treatment in a wide spectrum of depressed patients including atypical depression, bipolar depression, and refractory depression. Unfortunately, the clinical use of EMSAM has been underutilized and its potential usefulness overlooked. This article suggests that fear of possible side effects, particularly the “cheese reaction” and serotonin syndrome, are some of the main contributors to underutilization by clinicians. These risks have been significantly exaggerated with the 6 mg/day dose not even requiring a special diet. Other contributing factors leading to underutilization are reviewed such as: the lack of studies addressing many important clinical questions; inadequate data analyses; not evaluating the effect of EMSAM on comorbid psychiatric conditions, particularly anxiety disorders; lack of antidepressant comparators versus EMSAM; no dose–response relationship examined; various depressive subtypes and conditions are unexplored, eg, bipolar depression and refractory depression; poor insurance coverage for an expensive medication; as well as minimal marketing efforts and postmarketing studies. On the other hand, many potential advantages of EMSAM are not highlighted enough in the literature and by pharmaceutical companies which might have increased clinical interest and utilization of the antidepressant. For example, the advantages of EMSAM include: avoidance of swallowing issues, as can be seen with oral antidepressants; minimal side effects, probably due to a favorable pharmacokinetic profile; minimal evidence of suicidal behavior, probably relating to the transdermal route of administration; low rates of inducing hypomanic/manic episodes; as well as significant efficacy

  2. Reconsidering GHB: orphan drug or new model antidepressant?

    PubMed

    Bosch, Oliver G; Quednow, Boris B; Seifritz, Erich; Wetter, Thomas C

    2012-05-01

    For six decades, the principal mode of action of antidepressant drugs is the inhibition of monoamine re-uptake from the synaptic cleft. Tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs) and the new generation of dual antidepressants all exert their antidepressant effects by this mechanism. In the early days of the monoaminergic era, other efforts have been made to ameliorate the symptoms of depression by pharmacological means. The gamma-aminobutyric acid (GABA) system was and possibly still is one of the main alternative drug targets. Gammahydroxybutyrate (GHB) was developed as an orally active GABA analogue. It was tested in animal models of depression and human studies. The effects on sleep, agitation, anhedonia and depression were promising. However, the rise of benzodiazepines and tricyclic antidepressants brought GHB out of the scope of possible treatment alternatives. GHB is a GABA(B) and GHB receptor agonist with a unique spectrum of behavioural, neuroendocrine and sleep effects, and improves daytime sleepiness in various disorders such as narcolepsy, Parkinson's disease and fibromyalgia. Although it was banned from the US market at the end of the 1990s because of its abuse and overdose potential, it later was approved for the treatment of narcolepsy. New research methods and an extended view on other neurotransmitter systems as possible treatment targets of antidepressant treatment brought GHB back to the scene. This article discusses the unique neurobiological effects of GHB, its misuse potential and possible role as a model substance for the development of novel pharmacological treatment strategies in depressive disorders. PMID:21926421

  3. Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat.

    PubMed

    Antkiewicz-Michaluk, Lucyna; Wąsik, Agnieszka; Możdżeń, Edyta; Romańska, Irena; Michaluk, Jerzy

    2014-07-01

    Animal models are widely used to study antidepressant-like effect in rodents. However, it should be mentioned that pharmacological models do not always take into account the complexity of the disease process. In the present paper, we demonstrated that repeated but not acute treatment with a low dose of reserpine (0.2 mg/kg i.p.) led to a pharmacological model of depression which was based on its inhibitory effect on the vesicular monoamine transporter 2, and monoamines depleting action in the brain. In fact, we observed that chronic treatment with a low dose of reserpine induced a distinct depressive-like behavior in the forced swim test (FST), and additionally, it produced a significant decrease in the level of dopamine, noradrenaline, and serotonin in the brain structures. 1,2,3,4-Tetrahydroisoquinoline (TIQ) and its close methyl derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) are exo/endogenous amines present naturally in the mammalian brain which demonstrated a significant antidepressant-like effect in the FST and the reserpine model of depression in the rat. Both compounds, TIQ and 1MeTIQ, administered chronically in a dose of 25 mg/kg (i.p.) together with reserpine completely antagonized reserpine-produced depression as assessed by the immobility time and swimming time. Biochemical data were in agreement with behavioral experiments and demonstrated that chronic treatment with a low dose of reserpine in contrast to acute administration produced a significant depression of monoamines in the brain structures and impaired their metabolism. These neurochemical effects obtained after repeated reserpine (0.2 mg/kg i.p.) in the brain structures were completely antagonized by joint TIQ or 1MeTIQ (25 mg/kg i.p.) administration with chronic reserpine. A possible molecular mechanism of action of TIQ and 1MeTIQ responsible for their antidepressant action is discussed. On the basis of the presented behavioral and biochemical studies, we suggest that both

  4. Non-responders to cardiac resynchronization therapy: the magnitude of the problem and the issues.

    PubMed

    Auricchio, Angelo; Prinzen, Frits W

    2011-01-01

    A variable proportion of cardiac resynchronization therapy (CRT) patients do not benefit from treatment (termed `non-responders'). The problem of non-response to CRT might become increasingly important, because it is anticipated that larger groups of heart failure patients are indicated to the therapy. This article will discuss the definition of response to CRT, the parameters related to response to CRT, and finally whether response to CRT might be predicted. The effort to improve patient selection in order to maximize human and financial resource utilization has fallen short so far. It is, however, conceivable that rather than the identification of a `universally' applicable cut-off value, risk strata-in which inclusion of method for determination of left ventricular volumes, etiology, QRS duration and morphology, etc-might better serve the goal of defining non-responders. Potentially simple clinical scores might help in refining outcome and by doing so, allow to more precisely measure response to CRT in daily practice in the individual patient at the time of CRT implantation. Although sophisticated cardiac imaging modalities have been intensively utilized for improving patient outcome, it seems that many mechanical dyssynchrony measures suffer from technical limitations and from difficult interpretation of the complex signals, which lack reproducibility outside highly specialized laboratories. PMID:21325727

  5. Leptin: a potential novel antidepressant.

    PubMed

    Lu, Xin-Yun; Kim, Chung Sub; Frazer, Alan; Zhang, Wei

    2006-01-31

    Leptin, a hormone secreted from adipose tissue, was originally discovered to regulate body weight. The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes. Here, we show that rats exposed to chronic unpredictable stress and chronic social defeat exhibit low leptin levels in plasma. Systemic leptin treatment reversed the hedonic-like deficit induced by chronic unpredictable stress and improved behavioral despair dose-dependently in the forced swim test (FST), a model widely used for screening potential antidepressant efficacy. The behavioral effects of leptin in the FST were accompanied by increased neuronal activation in limbic structures, particularly in the hippocampus. Intrahippocampal infusion of leptin produced a similar antidepressant-like effect in the FST as its systemic administration. By contrast, infusion of leptin into the hypothalamus decreased body weight but had no effect on FST behavior. These findings suggest that: (i) impaired leptin production and secretion may contribute to chronic stress-induced depression-like phenotypes, (ii) the hippocampus is a brain site mediating leptin's antidepressant-like activity, and (iii) elevating leptin signaling in brain may represent a novel approach for the treatment of depressive disorders. PMID:16423896

  6. Leptin: A potential novel antidepressant

    PubMed Central

    Lu, Xin-Yun; Kim, Chung Sub; Frazer, Alan; Zhang, Wei

    2006-01-01

    Leptin, a hormone secreted from adipose tissue, was originally discovered to regulate body weight. The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes. Here, we show that rats exposed to chronic unpredictable stress and chronic social defeat exhibit low leptin levels in plasma. Systemic leptin treatment reversed the hedonic-like deficit induced by chronic unpredictable stress and improved behavioral despair dose-dependently in the forced swim test (FST), a model widely used for screening potential antidepressant efficacy. The behavioral effects of leptin in the FST were accompanied by increased neuronal activation in limbic structures, particularly in the hippocampus. Intrahippocampal infusion of leptin produced a similar antidepressant-like effect in the FST as its systemic administration. By contrast, infusion of leptin into the hypothalamus decreased body weight but had no effect on FST behavior. These findings suggest that: (i) impaired leptin production and secretion may contribute to chronic stress-induced depression-like phenotypes, (ii) the hippocampus is a brain site mediating leptin's antidepressant-like activity, and (iii) elevating leptin signaling in brain may represent a novel approach for the treatment of depressive disorders. PMID:16423896

  7. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    PubMed

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  8. Placebo-Activated Neural Systems are Linked to Antidepressant Responses

    PubMed Central

    Peciña, Marta; Bohnert, Amy S. B.; Sikora, Magdalena; Avery, Erich T.; Langenecker, Scott A.; Mickey, Brian J.; Zubieta, Jon-Kar

    2016-01-01

    Importance High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. Objective Here we examined neurochemical mechanisms underlying the formation of placebo effects in patients with Major Depressive Disorder (MDD). Participants Thirty-five medication-free MDD patients. Design and Intervention We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either “active” or “inactive” fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the μ-opioid receptor (MOR)-selective radiotracer [11C]carfentanil after each 1-week “inactive” and “active” oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Setting A University Health System. Main Outcomes and Measures Changes in depressive symptoms in response to “active” placebo and antidepressant. Baseline and activation measures of MOR binding. Results Higher baseline MOR binding in the nucleus accumbens (NAc) was associated with better response to antidepressant treatment (r=0.48; p=0.02). Reductions in depressive symptoms after 1-week of “active” placebo treatment, compared to the “inactive”, were associated with increased placebo-induced μ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the

  9. Identification and Treatment of Antidepressant Tachyphylaxis

    PubMed Central

    2014-01-01

    Antidepressant tachyphylaxis describes a condition in which a depressed patient loses a previously effective antidepressant treatment response despite staying on the same drug and dosage for maintenance treatment. It has been suggested that antidepressant tachyphylaxis is a form of relapse related to evolving drug tolerance, but it is also clear that there are other possible reasons for the loss of treatment response unrelated to tolerance, such as medication nonadherence. It has been reported that depressed patients with “true” antidepressant tachyphylaxis may be less responsive to new treatment interventions. Therefore, it is important to identify these patients as part of a comprehensive treatment planning process. PMID:24800130

  10. Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

    PubMed Central

    Andrews, Paul W.; Thomson, J. Anderson; Amstadter, Ananda; Neale, Michael C.

    2012-01-01

    Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of

  11. Repeated ketamine administration redeems the time lag for citalopram's antidepressant-like effects.

    PubMed

    Zhang, G-F; Liu, W-X; Qiu, L-L; Guo, J; Wang, X-M; Sun, H-L; Yang, J-J; Zhou, Z-Q

    2015-06-01

    Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects. PMID:25795441

  12. Antidepressant treatment for depression: total charges and therapy duration*

    PubMed

    Dobrez, Deborah G.; Melfi, Catherine A.; Croghan, Thomas W.; Kniesner, Thomas J.; Obenchain, Robert L.

    2000-12-01

    BACKGROUND: The economic costs of depression are significant, both the direct medical costs of care and the indirect costs of lost productivity. Empirical studies of antidepressant cost-effectiveness suggest that the use of selective serotonin reuptake inhibitors (SSRIs) may be no more costly than tricyclic antidepressants (TCAs), will improve tolerability, and is associated with longer therapy duration. However the success of depression care usually involves multiple factors, including source of care, type of care, and patient characteristics, in addition to drug choice. The cost-effective mix of antidepressant therapy components is unclear. AIMS OF THE STUDY: Our study evaluates cost and antidepressant-continuity outcomes for depressed patients receiving antidepressant therapy. Specifically, we determined the impact of provider choice for initial care, concurrent psychotherapy, and choice of SSRI versus TCA-based pharmacotherapies on the joint outcome of low treatment cost and continuous antidepressant therapy. METHODS: A database of private health insurance claims identifies 2678 patients who received both a diagnosis of depression and a prescription for an antidepressant during 1990-1994. Patients each fall into one of four groups according to whether their health care charges are high versus low (using the median value as the break point) and by whether their antidepressant usage pattern is continuous versus having discontinued pharmacotherapy early (filling fewer than six prescriptions). A bivariate probit model controlling for patient characteristics, co-morbidities, type of depression and concurrent treatment is the primary multivariate statistical vehicle for the cost-effective treatment situation. RESULTS: SSRIs substantially reduce the incidence of patients discontinuing pharmacotherapy while leaving charges largely unchanged. The relative effectiveness of SSRIs in depression treatment is independent of the patient's personal characteristics and

  13. The Efficacies and Toxicities of Antidepressant Drugs in Clinics, Building the Relationship between Chemo-Genetics and Socio-Environments.

    PubMed

    Lu, Da-Yong; Lu, Ting-Ren; Zhu, Peng-Peng; Che, Jin-Yu

    2015-01-01

    Antidepressants generally relief human depressive symptoms and help depressed people. Nevertheless, some undesired clinical events, such as suicide have been emerging more recently. In order to improve and promote antidepressant utilizations in clinics, new researches are focusing on reevaluation of the relationship between efficacy and toxicities of antidepressants in China and US. These researches speed up quickly. Many creative ideas and discoveries have been made, including predictions of the efficacies and toxicities of antidepressants under the same evaluating systems (pharmacogenetics and bioinformatics), genome-wide associate study (GWAS) of the relationship between individual genetic factors and therapeutic outcomes of different types of antidepressants and socio-environmental factors. Hopefully, therapeutic efficacies and outcomes by different types of antidepressant treatments for patients can be improved in clinical trials in the near future. PMID:25924829

  14. Suicidality and antidepressants in the elderly

    PubMed Central

    2008-01-01

    Suicide has reached epidemic proportions in the elderly, particularly in non-Hispanic white men. Unfortunately, the risk is underappreciated in this population. Known risk correlates for suicide in this population fall into three interrelated categories. Sociologic factors include such considerations as living alone and having few social interactions. Physical health factors include having more medical comorbidity and being a current smoker. The mental health risk factors include the presence of mood and anxiety disorders with a focus on the greater severity of symptoms, especially hypersomnia, hopelessness, and a history of suicide attempts. Suicide is a spectrum comprising ideation, intent, and plan. Clinical depression is never a normal part of aging and warrants aggressive treatment. Recent warnings linking antidepressants and suicide may have special relevance in the elderly. Based on preliminary studies with antipsychotic drugs, a subgroup of patients who experience akathisia may be particularly vulnerable to suicide. Upon initiation of antidepressants, it is recommended that adults be seen in follow-up three times within the first 12 weeks of treatment; if medically indicated, the first contact should be during the first week. PMID:18982077

  15. The unfulfilled promise of the antidepressant medications.

    PubMed

    Davey, Christopher G; Chanen, Andrew M

    2016-05-16

    Australia has one of the highest rates of antidepressant use in the world; it has more than doubled since 2000, despite evidence showing that the effectiveness of these medications is lower than previously thought. An increasing placebo response rate is a key reason for falling effectiveness, with the gap between response to medications and placebo narrowing. Psychotherapies are effective treatments, but recent evidence from high-quality studies suggests that their effectiveness is also modest. Combined treatment with medication and psychotherapy provides greater effectiveness than either alone. The number of patients receiving psychotherapy had been declining, although this trend is probably reversing with the Medicare Better Access to Mental Health Care initiative. Antidepressant medications still have an important role in the treatment of moderate to severe depression; they should be provided as part of an overall treatment plan that includes psychotherapy and lifestyle strategies to improve diet and increase exercise. When medications are prescribed, they should be used in a way that maximises their chance of effectiveness. PMID:27169968

  16. Structure-activity relationships and molecular studies of novel arylpiperazinylalkyl purine-2,4-diones and purine-2,4,8-triones with antidepressant and anxiolytic-like activity.

    PubMed

    Zagórska, Agnieszka; Kołaczkowski, Marcin; Bucki, Adam; Siwek, Agata; Kazek, Grzegorz; Satała, Grzegorz; Bojarski, Andrzej J; Partyka, Anna; Wesołowska, Anna; Pawłowski, Maciej

    2015-06-01

    A novel series of arylpiperazinylalkyl purine-2,4-diones (4-27) and purine-2,4,8-triones (31-38) was synthesized and tested to evaluated their affinity for the serotoninergic (5-HT1A, 5-HT6, 5-HT7) and dopaminergic (D2) receptors. Compounds with purine-2,4-dione nucleus generally had affinity values higher than the corresponding purine-2,4,8-trione compounds. A spectrum of receptor activities was observed for compounds with a substituent at the 7-position of the imidazo[2,1-f]purine-2,4-dione system and some potent 5-HT1A (18, 25), 5-HT7 (14) and mixed 5-HT1A/5-HT7 (8, 9) receptor ligands with additional affinity for dopamine D2 receptors (15) has been identified. Moreover, docking studies proved that a substituent at the 7-position of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione could be essential for receptor affinity and selectivity, especially towards 5-HT1A and 5-HT7. The results of the preliminary pharmacological in vivo studies of selected derivatives of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione, including 9 as a potential anxiolytic, 8 and 15 as potential antidepressants, and 18 and 25 as potential antidepressant and anxiolytic agents. PMID:25965777

  17. p11 and its role in depression and therapeutic responses to antidepressants

    PubMed Central

    Svenningsson, Per; Kim, Yong; Warner-Schmidt, Jennifer; Oh, Yong-Seok; Greengard, Paul

    2014-01-01

    Studies of the multifunctional protein p11 (also known as S100A10) are shedding light on the molecular and cellular mechanisms underlying depression. Here we review data implicating p11 in both the amplification of serotonergic signaling and the regulation of gene transcription. We summarize studies demonstrating that the levels of p11 are regulated in depression and by antidepressant regimens and, conversely, that p11 regulates depression-like behaviors and/or responses to antidepressants. Current and future studies of p11 may provide a molecular and cellular framework for the development of novel antidepressant therapies. PMID:24002251

  18. Antidepressants as analgesics: an overview of central and peripheral mechanisms of action.

    PubMed Central

    Sawynok, J; Esser, M J; Reid, A R

    2001-01-01

    Antidepressants, given systemically, are widely used for the treatment of various chronic and neuropathic pain conditions in humans. In animal studies, antidepressants exhibit analgesic properties in nociceptive, inflammatory and neuropathic test systems, with outcomes depending on the specific agent, the particular test, the route of administration and the treatment method used. Although early studies focused on central (i.e., supraspinal, spinal) actions, more recent studies have demonstrated a local peripheral analgesic effect of antidepressants. These peripheral actions raise the possibility that topical formulations of antidepressants may be a useful alternative drug delivery system for analgesia. Antidepressants exhibit a number of pharmacological actions: they block reuptake of noradrenaline and 5-hydroxytryptamine, have direct and indirect actions on opioid receptors, inhibit histamine, cholinergic, 5-hydroxytryptamine and N-methyl-D-aspartate receptors, inhibit ion channel activity, and block adenosine uptake. The involvement of these mechanisms in both central and peripheral analgesia produced by antidepressants is considered. Data illustrating the preclinical peripheral analgesic actions of antidepressants are presented, as are some aspects of the mechanisms by which these actions occur. PMID:11212590

  19. Antidepressants relevant to oral and maxillofacial surgical practice

    PubMed Central

    Lambrecht, J. Thomas; Greuter, Christian; Surber, Christian

    2013-01-01

    Background: Depression is commonly associated with a high-carbohydrate diet, lack of interest in proper oral hygiene and xerostomia connected to the use of antidepressants. Patients often consult their dentists as a result of changes affecting the hard dental substance and the soft-tissues. Aim: The aim of this study was to identify adverse drug interactions between the antidepressants and medications commonly administered in dentistry in order to give practicing dentists an overview of the scientific literature. Objective: The objective is to identify the adverse drug interactions between antidepressants and medication commonly administered in dentistry. Study Design: The literature search was performed using PubMed, Cochrane and the specific search items. The review (1984-2009) focused on medicines used in dental practice (vasoconstrictors, non-opioid analgesics, non-steroidal anti-inflammatory drugs, antibiotics, antifungals and benzodiazepines). Results: There are various drug interactions between antidepressants and medicines used in dentistry. When two or more drugs are co-administered, a drug interaction must always be anticipated though many of the interactions are potential problems, but do not seem to be real clinical issues. Conclusion: The probability of a drug interaction can be minimized by careful history-taking, skillful dose adjustment and safe administration of the therapeutic agent. PMID:24205476

  20. Long-term treatment with the combination of amantadine and ribavirin in hepatitis C nonresponders. A case series.

    PubMed

    Riley, Thomas R; Taheri, Mohammad R

    2007-12-01

    In this report, we describe five cases of chronic hepatitis C that have been treated with the combination of amantadine and ribavirin for an average of 44 months, emphasizing one case where the patient showed improvement in liver biopsy after treatment, worsening on removal, then a repeated improvement with re-initiation. The five patients in this report belong to a pool of sixty patients from a 6 month pilot study using amantadine and ribavirin where treatment was subsequently continued. The mean ALT was 82.8+/-32 U/L pre-treatment and 33.8+/-17.3 U/L post-treatment (p=0.02). The mean Knodell score was 7+/-1 pre-treatment and 3.6+/-1.5 post-treatment (p=0.13). The mean viral load was 584,155+/-248,027 lU/ml pre-treatment and 225,878+/-190,143 IU/ml post-treatment (p=0.05). In this case series we provide provocative data on the long-term use of ribavirin and amantadine in the HCV non-responder. PMID:17401686

  1. Antibody response to revaccination among adult non-responders to primary Hepatitis B vaccination in China

    PubMed Central

    Zhang, Li; Liu, Jiaye; Lu, Jingjing; Yan, Bingyu; Song, Lizhi; Li, Li; Cui, Fuqiang; Zhang, Guomin; Wang, Fuzhen; Liang, Xiaofeng; Xu, Aiqiang

    2015-01-01

    About 10% adult failed to develop antibody response after primary hepatitis B vaccination, and revaccination may be an option to improve immune response, but the antibody responses to revaccination in adult non-responders have not been fully examined. Adult non-responders to primary 3-dose hepatitis B vaccination were randomly divided into 2 groups and revaccinated with 20 μg hepatitis B vaccine (HepB) derived from Saccharomyces Cerevisiae (HepB-SC) or 20 μg HepB derived from Chinese hamster ovary cells (HepB-CHO), respectively, at 0-, 1-, 6- month. Seroconversion rate and titer of antibody against hepatitis B surface antigen (anti-HBs) was measured one month after the 1st and 3rd revaccination dose. Anti-HBs seroconversion rates significantly increased from 54.98% [95% confidence interval (CI) 48.60%–61.24%] after the 1st revaccination dose to 89.24% (95% CI: 84.74%–92.79%) after the 3rd revaccination dose (P < 0.001), and the geometric mean titer (GMT) of anti-HBs increased from 12.18mIU/ml (95%CI: 7.81–18.98 mIU/ml) to 208.31 mIU/ml (95% CI: 148.87–291.47 mIU/ml) (P = 0.008).Compared with those with anti-HBs titer <2 mIU/ml after primary vaccination, those with antibody titer ≥2 mIU/ml after primary vaccination had higher seroconversion rate after the 1st dose revaccination (38.36% vs. 78.10%, P < 0.001) and after the 3rd dose of revaccination (84.25% vs. 96.19%, P = 0.003), and had higher antibody titer after the 1st dose of revaccination (3.32mIU/ml vs. 74.21mIU/ml, P < 0.0001) and after the 3rd dose of revaccination (145.73mIU/ml vs. 342.34mIU/ml, P = 0.01). Anti-HBs titer was significantly higher in those revaccinated with HepB-CHO than those revaccinated with HepB-SC after the 3rd dose (131.46 mIU/ml vs. 313.38mIU/ml, P = 0.01). Revaccination on adult HepB non-responders increased the immune response to HepB and may confer further protection against hepatitis B virus infection. If possible, revaccination might be an option to HepB non-responders

  2. Modulation of muscarinic system with serotonin-norepinephrine reuptake inhibitor antidepressant attenuates depression in mice

    PubMed Central

    Singh, Paramdeep; Singh, Thakur Gurjeet

    2015-01-01

    Objective: Several studies suggest that muscarinic receptor antagonist scopolamine is a rapidly acting antidepressant for the treatment-resistant depression. Therefore, this study was carried out to investigate the possibility of synergistic potential of scopolamine with antidepressants for the treatment of depression without memory impairment in mice. Materials and Methods: Antidepressants such as citalopram, duloxetine, fluvoxamine, and venlafaxine at their median effective dose that is 12.5, 42.8, 17.5, 15.7 mg/kg p.o., respectively, were evaluated in combination with scopolamine 0.2 mg/kg intraperitoneally for the synergistic potential for ameliorating depression in Swiss albino mice. A battery of tests including forced swim test (FST) and tail suspension test (TST) were performed in all the groups comprising vehicle control, scopolamine, antidepressants per se, and the combinations of antidepressants with scopolamine. This was followed by the locomotor activity and memory tests. Results: Behavioral studies indicated that only antidepressant venlafaxine with scopolamine resulted in 95.5% and 93.6% reduction in immobility time compared to the vehicle control in FST and TST, respectively. This is significant (P < 0.0001) synergistic hyper-additive antidepressive-like effect compared to scopolamine per se and venlafaxine per se treatment effects in antidepressant paradigms. All the data were evaluated using the one-way analysis of variance followed by individual comparisons using Tukey's post-hoc test. Control open field studies demonstrated no significant increase in general locomotion after co-administration of the compounds. Step down avoidance paradigm confirmed that scopolamine at the selected dose has no cognition deficit in any mice. Conclusions: The dose of scopolamine selected for synergistic potential has no detrimental effect on memory. The present results suggest the concoction of scopolamine with venlafaxine for enhanced synergistic antidepressive

  3. New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial).

    PubMed

    Peymani, Payam; Yeganeh, Behzad; Sabour, Siamak; Geramizadeh, Bita; Fattahi, Mohammad Reza; Keyvani, Hossein; Azarpira, Negar; Coombs, Kevin M; Ghavami, Saied; Lankarani, Kamran B

    2016-06-01

    Hepatitis C virus (HCV) infection induces autophagy, but the virus assimilates the autophagic response into its own life cycle. Chloroquine (CQ) is an autophagy inhibitor that is clinically used to treat malaria. The aims of this pilot clinical trial were to evaluate the therapeutic potential and short-term safety of CQ in patients with chronic HCV genotype 1, who were unresponsive to a combination of pegylated interferon alpha and ribavirin. Ten non-responders to previous antiviral treatment(s) were randomized to receive either CQ (150 mg daily for 8 weeks) or placebo, and were followed for 4 weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week 4 (initial response), week 8 (end-of-treatment response), and at the end of 12 weeks. A significant decrease in HCV RNA after the treatments (week 8) was observed in all patients in the CQ group (P = 0.04). However, HCV RNA levels increased within 4 weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalized during treatment in the CQ group. However, this response was also lost after treatment cessation. This study provides preliminary evidence that CQ is possibly a safe treatment option for HCV non-responders. PMID:26998724

  4. Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and β-thalassemia major.

    PubMed

    Bao, Weili; Zhong, Hui; Li, Xiaojuan; Lee, Margaret T; Schwartz, Joseph; Sheth, Sujit; Yazdanbakhsh, Karina

    2011-12-01

    Red blood cell alloimmunization is a major complication of transfusion therapy. Host immune markers that can predict antibody responders remain poorly described. As regulatory T cells (Tregs) play a role in alloimmunization in mouse models, we analyzed the Treg compartment of a cohort of chronically transfused patients with sickle cell disease (SCD, n = 22) and β-thalassemia major (n = 8) with and without alloantibodies. We found reduced Treg activity in alloantibody responders compared with nonresponders as seen in mice. Higher circulating anti-inflammatory IL-10 levels and lower IFN-γ levels were detected in non-alloimmunized SCD patients. Stimulated sorted CD4+ cells from half of the alloimmunized patients had increased frequency of IL-4 expression compared with nonresponders, indicating a skewed T helper (Th) 2 humoral immune response in a subgroup of antibody responders. All patients had increased Th17 responses, suggesting an underlying inflammatory state. Although small, our study indicates an altered immunoregulatory state in alloantibody responders which may help future identification of potential molecular risk factors for alloimmunization. PMID:21953592

  5. The discovery of antidepressant drugs by computer-analyzed human cerebral bio-electrical potentials (CEEG).

    PubMed

    Itil, T M

    1983-01-01

    Antidepressant properties of six compounds were predicted based on their computer-analyzed human electroencephalographical (CEEG) profiles. The clinical investigations with mianserin (GB-94) confirmed the CEEG prediction. This compound has now been marketed as the first antidepressant of which the clinical effects were discovered solely by the quantitative pharmaco-EEG method. As predicted by the CEEG, clinical antidepressant properties of GC-46, mesterolone, and estradiol valerate were observed in preliminary investigations. No extensive studies with definite statistical results were yet carried out with these compounds. No systematic large studies could be conducted with cyclozocine and cyproterone acetate because of the intolerable side effects with these compounds. The optical isomers of mianserin, GF-59 and GF-60, both predicted as antidepressant by the computer EEG data base, have not yet been tested in depressive patients. None of these compounds possess the "typical" pharmacological and/or biochemical profiles of marketed antidepressants. Thus, the discovery of the established antidepressant properties of mianserin (GB-94) by computer analyzed EEG method challenges the well-known biochemical hypotheses of depression and the "classical" development of antidepressant drugs. PMID:6142498

  6. Relevant issues in the monitoring and the toxicology of antidepressants.

    PubMed

    Wille, Sarah M R; Cooreman, Sarah G; Neels, Hugo M; Lambert, Willy E E

    2008-01-01

    This review provides specific information concerning the interpretation and usefulness of antidepressant drug monitoring. Fifteen antidepressants (ADs) were selected based on their importance in the 7 major markets (Japan, USA, France, United Kingdom, Italy, Spain, Germany) according to the Cognos Plus Study #11. Literature data were reviewed concerning monitoring of the tricyclic ADs amitriptyline, clomipramine, imipramine, and new generation antidepressants such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, mianserin, mirtazapine, bupropion, and milnacipran. In addition, St.-John's Wort was added as this natural antidepressant is very popular in Europe. The objectives of therapeutic drug monitoring (TDM) for old and new generation ADs differs, as older ADs have narrow therapeutic windows with higher risks of severe drug interactions, while the new ADs have a wide therapeutic range, but an unclear plasma concentration-effect relationship. Therefore, the purpose of TDM for new-generation ADs leads more to the monitoring of patient compliance and special patient groups such as the elderly, patients with liver and kidney impairment, patients with poor metabolism by CYP 450 and comedication with inhibitors and inducers of those enzymes. PMID:18293180

  7. Drug interactions with vortioxetine, a new multimodal antidepressant.

    PubMed

    Spina, Edoardo; Santoro, Vincenza

    2015-01-01

    This article summarized the available knowledge on clinically relevant drug interactions of vortioxetine, a new antidepressant with a “multimodal” serotonergic mechanism of action, recently approved for the treatment of major depressive disorder. Although information is still limited and mainly based on studies performed in healthy volunteers, vortioxetine appears to have a favorable drug interaction profile. Concerning the potential for pharmacokinetic drug interactions, vortioxetine has little to no effect on various cytochrome P450 (CYP) isoforms and therefore is not expected to markedly affect plasma concentrations of other medications metabolized by these enzymes. This is a major advantage when compared to other antidepressants which are known to inhibit the activity of one or more CYP isoforms. On the other hand, dosage adjustments may be required when vortioxetine is coadministered with strong CYP2D6 inhibitors or broad-spectrum CYP inducers. Vortioxetine carries a relatively low risk for pharmacodynamic drug interactions, at least as compared to first-generation antidepressants. Like other antidepressants enhancing serotonergic activity, vortioxetine is associated with a potential risk of serotonin syndrome when used in combination with other serotonergic agents. Based on all available clinical data, vortioxetine has no increased risk of serotonin syndrome when used without other serotoninergic agents and at therapeutic doses. PMID:26489070

  8. The effects of antenatal depression and antidepressant treatment on placental gene expression

    PubMed Central

    Olivier, Jocelien D. A.; Åkerud, Helena; Skalkidou, Alkistis; Kaihola, Helena; Sundström-Poromaa, Inger

    2015-01-01

    The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy. Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample. In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well. PMID:25628539

  9. The biological effects of antidepressants on the molluscs and crustaceans: a review.

    PubMed

    Fong, Peter P; Ford, Alex T

    2014-06-01

    Antidepressants are among the most commonly detected human pharmaceuticals in the aquatic environment. Since their mode of action is by modulating the neurotransmitters serotonin, dopamine, and norepinephrine, aquatic invertebrates who possess transporters and receptors sensitive to activation by these pharmaceuticals are potentially affected by them. We review the various types of antidepressants, their occurrence and concentrations in aquatic environments, and the actions of neurohormones modulated by antidepressants in molluscs and crustaceans. Recent studies on the effects of antidepressants on these two important groups show that molluscan reproductive and locomotory systems are affected by antidepressants at environmentally relevant concentrations. In particular, antidepressants affect spawning and larval release in bivalves and disrupt locomotion and reduce fecundity in snails. In crustaceans, antidepressants affect freshwater amphipod activity patterns, marine amphipod photo- and geotactic behavior, crayfish aggression, and daphnid reproduction and development. We note with interest the occurrence of non-monotonic dose responses curves in many studies on effects of antidepressants on aquatic animals, often with effects at low concentrations, but not at higher concentrations, and we suggest future experiments consider testing a broader range of concentrations. Furthermore, we consider invertebrate immune responses, genomic and transcriptomic sequencing of invertebrate genes, and the ever-present and overwhelming question of how contaminant mixtures could affect the action of neurohormones as topics for future study. In addressing the question, if antidepressants affect aquatic invertebrates at concentrations currently found in the environment, there is strong evidence to suggest the answer is yes. Furthermore, the examples highlighted in this review provide compelling evidence that the effects could be quite multifaceted across a variety of biological

  10. Antidepressants Impact Connexin 43 Channel Functions in Astrocytes

    PubMed Central

    Jeanson, Tiffany; Pondaven, Audrey; Ezan, Pascal; Mouthon, Franck; Charvériat, Mathieu; Giaume, Christian

    2016-01-01

    Glial cells, and in particular astrocytes, are crucial to maintain neuronal microenvironment by regulating energy metabolism, neurotransmitter uptake, gliotransmission, and synaptic development. Moreover, a typical feature of astrocytes is their high expression level of connexins, a family of membrane proteins that form gap junction channels allowing intercellular exchanges and hemichannels that provide release and uptake pathways for neuroactive molecules. Interestingly, several studies have revealed unexpected changes in astrocytes from depressive patients and rodent models of depressive-like behavior. Moreover, changes in the expression level of the astroglial connexin 43 (Cx43) have been reported in a depressive context. On the other hand, antidepressive drugs have also been shown to impact the expression of this connexin in astrocytes. However, so far there is little information concerning the functional consequence of these changes, i.e., the status of gap junctional communication and hemichannel activity in astrocytes exposed to antidepressants. In the present work we focused our attention on the action of seven antidepressants from four different therapeutic classes and tested their effects on Cx43 expression and on the two connexin-based channels functions studied in cultured astrocytes. We here report that when used at non-toxic and clinically relevant concentrations they have no effects on Cx43 expression but differential effects on Cx43 gap junction channels. Moreover, all tested antidepressants inhibit Cx43 hemichannel with different efficiency depending on their therapeutic classe. By studying the impact of antidepressants on the functional status of astroglial connexin channels, contributing to dynamic neuroglial interactions, our observations should help to better understand the mechanism by which these drugs provide their effect in the brain. PMID:26778961

  11. Antidepressant Use in Pregnancy and the Risk of Cardiac Defects

    PubMed Central

    Huybrechts, Krista F.; Palmsten, Kristin; Avorn, Jerry; Cohen, Lee S.; Holmes, Lewis B.; Franklin, Jessica M.; Mogun, Helen; Levin, Raisa; Kowal, Mary; Setoguchi, Soko; Hernandez-Diaz, Sonia

    2014-01-01

    Background There is controversy regarding whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants in pregnancy is associated with increased risks for congenital cardiac defects. In particular, concerns exist about a possible association between paroxetine and right ventricular outflow tract obstruction (RVOTO), and between sertraline and ventricular septal defects (VSD). Methods We performed a cohort study nested in the 2000–2007 nationwide Medicaid Analytic eXtract. The study included 949,504 pregnant women enrolled in Medicaid from three months before conception through one month post delivery, and their live-born infants. We compared the risk of major cardiac defects in women with antidepressant medication use during the first trimester versus no use, restricting the cohort to women with depression and using propensity score adjustment to control for depression severity and other potential confounders. Results 64,389 women (6.8%) used antidepressants during the first trimester. Overall, 6,403 infants not exposed to antidepressants were born with a cardiac defect (72.3 per 10,000), compared with 580 infants exposed (90.1 per 10,000). Associations between antidepressant use and cardiac defects were attenuated with increasing levels of adjustment for confounding. For SSRIs, relative risks for any cardiac defect were 1.25 (95%CI, 1.13–1.38) unadjusted, 1.12 (1.00–1.26) depression-restricted, and 1.06 (0.93–1.22) depression-restricted and fully-adjusted. We found no significant associations between the use of paroxetine and RVOTO (1.07, 0.59–1.93), or the use of sertraline and VSD (1.04, 0.76–1.41). Conclusions Results of this large population-based cohort study suggest no substantial increased risk of cardiac malformations attributable to SSRIs. PMID:24941178

  12. Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine.

    PubMed Central

    Banerjee, S; Hellier, J; Romeo, R; Dewey, M; Knapp, M; Ballard, C; Baldwin, R; Bentham, P; Fox, C; Holmes, C; Katona, C; Lawton, C; Lindesay, J; Livingston, G; McCrae, N; Moniz-Cook, E; Murray, J; Nurock, S; Orrell, M; O'Brien, J; Poppe, M; Thomas, A; Walwyn, R; Wilson, K; Burns, A

    2013-01-01

    (44/108, 41%; p = 0.017); 39-week mortality equal, five deaths in each group. CONCLUSIONS: This is a trial with negative findings but important clinical implications. The data suggest that the antidepressants tested, given with normal care, are not clinically effective (compared with placebo) for clinically significant depression in AD. This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD. From the data generated we formulated the following recommendations for future work. (1) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia. (2) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm. (3) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life, but also the time they spend care-giving. (4) There is a need for research into alternative biological and psychological therapies for depression in dementia. These could include evaluations of new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g. cholinesterase inhibitors). (5) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services. (6) Further work is needed to investigate the cost modelling results in this rich data set, investigating carer burden and possible moderators to the treatment effects. (7) There is scope for reanalysis of the primary outcome in terms of carer and participant CSDD results. PMID:23438937

  13. Antidepressant pharmacotherapy: economic outcomes in a health maintenance organization.

    PubMed

    Sclar, D A; Robison, L M; Skaer, T L; Legg, R F; Nemec, N L; Galin, R S; Hughes, T E; Buesching, D P

    1994-01-01

    Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin re-uptake inhibitors (SSRIs). The present study was designed to contrast direct health service expenditures for the treatment of depression among patients enrolled in a health maintenance organization (HMO) and prescribed either the SSRI fluoxetine or one of three tricyclic antidepressants (TCAs) (amitriptyline, nortriptyline, or desipramine). Information regarding health service utilization was derived from the computer archive of a network-model HMO system serving 400,000 beneficiaries. A total of 701 HMO beneficiaries were found to satisfy the study selection criteria. Multivariate regression analysis was used to discern the incremental influence of selected demographic, clinical, financial, and provider characteristics on 1 year post-period expenditures (PPE) for health care. Analysis-of-variance procedures with Duncan's multiple-range test, or chi-square analyses, revealed no significant difference across antidepressant pharmacotherapy for age, sex, 6-month prior-period expenditures for physician visits, psychiatric visits, laboratory tests, hospitalizations, or psychiatric hospital services related to the treatment of depression, or number of prescribed therapeutic agents for disease state processes other than depression. Receipt of fluoxetine was associated with a significantly (P < or = 0.05) higher rate of initial prescribing by psychiatrists, an increase in the number of prescriptions for antidepressant pharmacotherapy obtained (30-day supplies), and a reduction in the number of monthly intervals during which time antidepressant pharmacotherapy was not procured. Receipt of fluoxetine as antidepressant pharmacotherapy was associated with a significantly (P < or = 0.05) higher mean medication possession ratio (MPR) relative to amitriptyline, nortriptyline, or desipramine. Multivariate findings for patient-level data reflecting a definitive

  14. Antidepressants in the Treatment of Functional Dyspepsia: A Systematic Review and Meta-Analysis

    PubMed Central

    Lu, Yaoyao; Chen, Meng; Huang, Zhiyin; Tang, Chengwei

    2016-01-01

    Background Antidepressants have been empirically used in the treatment of functional dyspepsia (FD). However, results from recent clinical trials investigating their efficacy are conflicting. The aim of this study is to evaluate the efficacy of antidepressants in the management of FD in adults. Methods Databases of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and BIOSIS Previews were searched for all randomized controlled trials (RCT) investigating efficacy of antidepressants in the management of FD in adult patients. Data of overall symptom unimproved and adverse events were compared between the antidepressants and placebo group. Results The search strategy identified 432 citations. Of those, eight RCTs met the inclusion criteria and were included in the meta-analysis. The pooled relative risk (RR) of symptom unimproved with tricyclic antidepressants (TCAs) versus placebo was 0.76 (95% CI: 0.62 to 0.94, P = 0.01; I2 = 0%, P = 0.39). By contrast, selective serotonin reuptake inhibitors (SSRIs) did not show a benefit over placebo (RR = 1.00, 95% CI: 0.86 to 1.17, P = 0.95; I2 = 0%, P = 0.82). Adverse events were significantly more frequent among patients receiving antidepressants than those receiving placebos (RR = 1.64, 95% CI: 1.14 to 2.35, P = 0.007). Conclusion TCAs but not SSRIs, are effective in the treatment of FD, but antidepressants were also associated with more adverse events compared with placebo. PMID:27310135

  15. REM sleep homeostasis in the absence of REM sleep: Effects of antidepressants.

    PubMed

    McCarthy, Andrew; Wafford, Keith; Shanks, Elaine; Ligocki, Marcin; Edgar, Dale M; Dijk, Derk-Jan

    2016-09-01

    Most antidepressants suppress rapid eye movement (REM) sleep, which is thought to be important to brain function, yet the resulting REM sleep restriction is well tolerated. This study investigated the impact of antidepressants with different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA), on the regulation of REM sleep in rats. REM sleep was first demonstrated to be homeostatically regulated using 5, 8 and 10 h of REM-sleep specific restriction through EEG-triggered arousals, with an average of 91 ± 10% of lost REM sleep recovered following a 26-29 -hour recovery period. Acute treatment with the antidepressants paroxetine, citalopram and imipramine inhibited REM sleep by 84 ± 8, 84 ± 8 and 69 ± 9% respectively relative to vehicle control. The pharmacologically-induced REM sleep deficits by paroxetine and citalopram were not fully recovered, whereas, after imipramine the REM sleep deficit was fully compensated. Given the marked difference between REM sleep recovery following the administration of paroxetine, citalopram, imipramine and REM sleep restriction, the homeostatic response was further examined by pairing REM sleep specific restriction with the three antidepressants. Surprisingly, the physiologically-induced REM sleep deficits incurred prior to suppression of REM sleep by all antidepressants was consistently recovered. The data indicate that REM sleep homeostasis remains operative following subsequent treatment with antidepressants and is unaffected by additional pharmacological inhibition of REM sleep. PMID:27150557

  16. Prescription pattern of antidepressants in five tertiary care psychiatric centres of India

    PubMed Central

    Tripathi, Adarsh; Avasthi, Ajit; Desousa, Avinash; Bhagabati, Dipesh; Shah, Nilesh; Kallivayalil, Roy Abraham; Grover, Sandeep; Trivedi, J.K.; Shinfuku, Naotaka

    2016-01-01

    Background & objectives: Limited data are available on prescription patterns of the antidepressants from India. We studied antidepressants’ prescription pattern from five geographically distant tertiary psychiatric care centers of the India. Method: In this cross-sectional study, all patients who attended outpatients department or were admitted in the psychiatry wards at Lucknow, Chandigarh, Tiruvalla, Mumbai and Guwahati on a fixed day, who were using or had been prescribed antidepressant medications, were included. The data were collected on a unified research protocol. Results: A total of 312 patients were included. Mean age was 39±14.28 yr and 149 (47.76%) were females, 277 (87.5%) were outpatients. Among the patients receiving antidepressants, 150 (48.1%) were of diagnoses other than depression. Diabetes mellitus 18 (5.78%) was the most common co-morbid medical illness. A total of 194 (62.2%) patients were using selective serotonin reuptake inhibitors (SSRIs) with escitalopram 114 (36.53%) being the most common antidepressant used. Overall, 272 (87.18%) patients were using newer antidepressants. Thirty (9.62%) were prescribed more than one antidepressant; 159 (50.96%) patients were prescribed hypnotic or sedative medications with clonazepam being the most common (n=116; 37.18%). Interpretation & conclusions: About half of the patients with diagnoses other than depression were prescribed antidepressants. SSRIs were the most common group and escitalopram was the most common medication used. Concomitant use of two antidepressants was infrequent. Hypnotic and sedatives were frequently prescribed along with antidepressants. PMID:27377509

  17. Association between antidepressants and falls in Parkinson's disease.

    PubMed

    Martinez-Ramirez, Daniel; Giugni, Juan C; Almeida, Leonardo; Walz, Roger; Ahmed, Bilal; Chai, Fiona A; Rundle-Gonzalez, Valerie; Bona, Alberto R; Monari, Erin; Wagle Shukla, Aparna; Hess, Christopher W; Hass, Chris J; Okun, Michael S

    2016-01-01

    Parkinson's disease (PD) patients have an increased risk of falls resulting in important social and economical consequences. Risk factors for falls include the use of psychotropic drugs, which are used for the treatment of PD neuropsychiatric symptoms. We aimed to determine the association between psychotropic drug use and falls in a PD cohort. A cross-sectional study from the NPF QII study UF site was conducted. Subjects reported presence and frequency of falls in the prior year. Frequency was scored from 0 (no falls) to 4 (falling daily). Antidepressants, antipsychotics, cognitive enhancers/stimulants, and benzodiazepines were considered psychotropics. Forty percent of the 647 subjects included had a fall in the previous year. Fallers were found to have clinical signs of a more advanced disease. After adjusting for confounding variables, the regression analysis showed that use of antidepressants alone (adjusted OR 2.2, CI 95 % 1.3-3.8, p = 0.04), benzodiazepines alone (adjusted OR 2.0, CI 95 % 1.1-3.5, p = 0.02), and the combination of antidepressants with benzodiazepines (adjusted OR 4.1, CI 95 % 2.0-8.3, p < 0.0001) were independently associated with the presence of falls. When comparing to those not on psychotropics, subjects on antidepressants alone had a significantly higher mean frequency of falls score (1.07 vs. 0.44, p < 0.0001). The use of antidepressants was independently associated with falls in our PD cohort after considering for confounding variables such as age and measures of disease progression. Other factors related to disease progression should be considered before claiming the use of psychotropic drugs as causative. PMID:26514836

  18. Invivo antioxidant status: a putative target of antidepressant action.

    PubMed

    Zafir, Ayesha; Ara, Anjum; Banu, Naheed

    2009-03-17

    Oxidative stress is a critical route of damage in various psychological stress-induced disorders, such as depression. Antidepressants are widely prescribed to treat these conditions; however, few animal studies have investigated the effect of these drugs on endogenous antioxidant status in the brain. The present study employed a 21-day chronic regimen of random exposure to restraint stress to induce oxidative stress in brain, and behavioural aberrations, in rodents. The forced swimming (FST) and sucrose preference tests were used to identify depression-like phenotypes, and reversal in these indices indicated the effectiveness of treatment with fluoxetine (FLU; 20 mg/kg/day, p.o.; selective serotonin reuptake inhibitor), imipramine (IMI; 10 mg/kg/day, p.o.; tricyclic antidepressant) and venlafaxine (VEN; 10 mg/kg/day, p.o.; dual serotonin/norepinephrine reuptake inhibitor) following restraint stress. The antioxidant status was investigated in the brain of these animals. The results evidenced a significant recovery in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione (GSH) levels by antidepressant treatments following a restraint stress-induced decline of these parameters. The severely accumulated lipid peroxidation product malondialdehyde (MDA) and protein carbonyl contents in stressed animals were significantly normalized by antidepressant treatments. The altered oxidative status is implicated in various aspects of cellular function affecting the brain. Thus, it is possible that augmentation of in vivo antioxidant defenses could serve as a convergence point for multiple classes of antidepressants as an important mechanism underlying the neuroprotective pharmacological effects of these drugs observed clinically in the treatment of various stress disorders. Consequently, pharmacological modulation of stress-induced oxidative damage as a possible stress-management approach should

  19. Duality of Antidepressants and Neuroprotectants.

    PubMed

    Tizabi, Yousef

    2016-07-01

    The co-morbidity of neuropsychiatric disorders, particularly major depressive disorder (MDD) with neurodegenerative diseases, in particular Parkinson's disease (PD) is now well recognized. Indeed, it is suggested that depressive disorders, especially in late life, may be an indication of latent neurodegeneration. Thus, it is not unreasonable to expect that deterrents of MDD may also deter the onset and/or progression of the neurodegenerative diseases including PD. In this review, examples of neuroprotective efficacy of established as well as prospective antidepressants are provided. Conversely, mood-regulating effects of some neuroprotective drugs are also presented. Thus, in addition to currently used antidepressants, ketamine, nicotine, curcumin, and resveratrol are discussed for their dual efficacy. In addition, potential neurobiological substrates for their actions are presented. It is concluded that pharmacological developments of mood-regulating or neuroprotective drugs can have cross benefit in co-morbid conditions of neuropsychiatric and neurodegenerative disorders and that inflammatory and neurotrophic factors play important roles in both conditions. PMID:26613895

  20. [Antidepressives and traffic safety].

    PubMed

    Herberg, K W

    1994-09-01

    The influence of paroxetine (1x20 mg/day) on safety-relevant performance was compared with the effects of doxepin (2x50 mg/day) and placebo. The medication covered a 3-week period. On day 20 of treatment, ethanol was additionally administered (0.05% BAC). The study group comprised 60 healthy male and female volunteers in the age range 37-60 years, who were assigned to the three structurally identical medication groups under randomized, double-blind conditions. The functional capacity of primary interest was investigated in seven tests to record visual orientation, forced concentration, simple reaction time, choice reaction time, reaction under stress, vigilance, and motor co-ordination. Test sessions took place before the treatment and five times during the medication phase. Paroxetine proved comparable to placebo in all cases, while in comparison with the two reference substances doxepin revealed loss of vigilance and motor coordination, as well as of concentration and the simple (acoustic) reaction time. PMID:7959523

  1. Factors Related to Outcome in a School-Based Intensive Mental Health Program: An Examination of Nonresponders

    ERIC Educational Resources Information Center

    Jacobs, Anne K.; Roberts, Michael C.; Vernberg, Eric M.; Nyre, Joseph E.; Randall, Camille J.; Puddy, Richard W.

    2008-01-01

    We examined factors related to treatment responders (n = 35) and nonresponders (n = 16) in a group of 51 children admitted to the Intensive Mental Health Program (IMHP). Children's response to treatment was coded based on their functioning at intake and discharge using total CAFAS scores. Demographic variables, length of treatment, number of…

  2. Risk of Suicidal Behavior With Antidepressants in Bipolar and Unipolar Disorders

    PubMed Central

    Leon, Andrew C; Fiedorowicz, Jess G.; Solomonon, David A.; Li, Chunshan; Coryell, William H.; Endicott, Jean; Fawcett, Jan; Keller, Martin B.

    2014-01-01

    Objective To examine the risk ofsuicidal behavior (suicide attempts and deaths) associated with antidepressants in participants with bipolar I, bipolar n, and unipolar major depressive disorders. Design A 27-year longitudinal (1981-2008) observational study ofmood disorders (Research Diagnostic Criteria diagnoses based on Schedule Dr Afi:ctive Disorders and Schizophrenia and review ofmedical records) was used to evaluate antidepressants and risk Dr suicidal behavior. Mixed-efi:cts logistic regression models examined propensity Dr antidepressant exposure. Mixed-efi:cts swvival models that were matched on the propensity score examined exposure status as a risk factor for time until suicidal behavior. Setting Five US academic medical centers. Results Analyses of206 participants with bipolar I disorder revealed 2,010 exposure intervals (980 exposed to antidepressants; 1,030 unexposed); 139 participants with bipolar II disorder had 1 ,407 exposure intervals (694 exposed; 713 unexposed); and 361 participants with unipolar depressive disorder had 2, 745 exposure intervals (1,328 exposed; 1,417 unexposed). Propensity score analyses confinned that more severely ill participants were more likely to initiate antidepressant treatment. In mixed-elects swvival analyses, those with bipolar I disorder had a significant reduction in risk of suicidal behavior by 54% (HR = 0.46; 95% CI, 0.31-0.69; t = -3.74; P < .001) during periods of antidepressant exposure compared to propensity-matched unexposed intervals. Similarly, the risk was reduced by 35% (HR = 0.65; 95% CI, 0.43-0.99; t = −2.01; P = .045) in bipolar II disorder. By contrast, there was no evidence of an increased or decreased risk with antidepressant exposure in unipolar disorder. Condusions Based on obsetVational data adjusted Dr propensity to receive antidepressants, antidepressants may protect patients with bipolar disorders but not unipolar depressive disorder from suicidal behavior. PMID:25093469

  3. Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.

    PubMed

    Bottonari, Kathryn A; Tripathi, Shanti P; Fortney, John C; Curran, Geoff; Rimland, David; Rodriguez-Barradas, Maria; Gifford, Allen L; Pyne, Jeffrey M

    2012-05-01

    Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n=146), an antiretroviral (n=192), or both (n=113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence" or "90% or greater adherence." After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n=146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n=112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n=113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (β=1.62, p=0.17), however, antidepressant adherence

  4. Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers

    MedlinePlus

    ... in Pediatric Antidepressant Treatment: A Meta-analysis of Randomized Controlled Trials. JAMA . 2007;297:1683-1696. Treatment ... depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial . Journal of the American Medical Association , ...

  5. Clinically significant drug interactions with newer antidepressants.

    PubMed

    Spina, Edoardo; Trifirò, Gianluca; Caraci, Filippo

    2012-01-01

    After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone. In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at

  6. Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

    PubMed Central

    Bourke, Chase H.; Stowe, Zachary N.

    2014-01-01

    Pharmacological treatment of any maternal illness during pregnancy warrants consideration of the consequences of the illness and/or medication for both the mother and unborn child. In the case of major depressive disorder, which affects up to 10–20% of pregnant women, the deleterious effects of untreated depression on the offspring can be profound and long lasting. Progress has been made in our understanding of the mechanism(s) of action of antidepressants, fetal exposure to these medications, and serotonin’s role in development. New technologies and careful study designs have enabled the accurate sampling of maternal serum, breast milk, umbilical cord serum, and infant serum psychotropic medication concentrations to characterize the magnitude of placental transfer and exposure through human breast milk. Despite this progress, the extant clinical literature is largely composed of case series, population-based patient registry data that are reliant on nonobjective means and retrospective recall to determine both medication and maternal depression exposure, and limited inclusion of suitable control groups for maternal depression. Conclusions drawn from such studies often fail to incorporate embryology/neurotransmitter ontogeny, appropriate gestational windows, or a critical discussion of statistically versus clinically significant. Similarly, preclinical studies have predominantly relied on dosing models, leading to exposures that may not be clinically relevant. The elucidation of a defined teratological effect or mechanism, if any, has yet to be conclusively demonstrated. The extant literature indicates that, in many cases, the benefits of antidepressant use during pregnancy for a depressed pregnant woman may outweigh potential risks. PMID:24567054

  7. Relabeling the Medications We Call Antidepressants

    PubMed Central

    Antonuccio, David; Healy, David

    2012-01-01

    This paper raises the question about whether the data on the medications we call antidepressants justify the label of antidepressant. The authors argue that a true antidepressant should be clearly superior to placebo, should offer a risk/benefit balance that exceeds that of alternative treatments, should not increase suicidality, should not increase anxiety and agitation, should not interfere with sexual functioning, and should not increase depression chronicity. Unfortunately, these medications appear to fall short on all of these dimensions. Many of the “side effects” of these medications have larger effect sizes than the antidepressant effect size. To call these medications antidepressants may make sense from a marketing standpoint but may be misleading from a scientific perspective. Consumers deserve a label that more accurately reflects the data on the largest effects and helps them understand the range of effects from these medications. In other words, it may make just as much sense to call these medications antiaphrodisiacs as antidepressants because the negative effects on libido and sexual functioning are so common. It can be argued that a misleading label may interfere with our commitment to informed consent. Therefore, it may be time to stop calling these medications antidepressants. PMID:24278764

  8. Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder

    PubMed Central

    McCarter, Stuart J.; St. Louis, Erik K.; Sandness, David J.; Arndt, Katlyn A.; Erickson, Maia K.; Tabatabai, Grace M.; Boeve, Bradley F.; Silber, Michael H.

    2015-01-01

    Study Objectives: REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. Design: We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. Setting: Tertiary-care sleep center. Participants: Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. Interventions: N/A. Measurements and Results: RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P < 0.01). RSWA distribution and type also differed between antidepressant-treated patients having higher values in anterior tibialis, and PD-RBD with higher submentalis and tonic RSWA. Psychiatric RBD had significantly younger age at onset than traditional RBD patients (P < 0.01). Conclusions: Antidepressant treatment was associated with elevated REM sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration

  9. Influence of depression and antidepressants on weight.

    PubMed

    Gottfries, C G

    1981-01-01

    Depression is often combined with loss of appetite and weight. Treatment with some psychotropic drugs, especially many of the tricyclic antidepressives, causes weight gain. Zimelidine, an antidepressive drug with selective inhibitory effect on the reuptake of 5-hydroxytryptamine (5-HT) causes no weight gain in treated patients. As even weight loss is seen it can be discussed whether the drug has an inhibitory effect on feeding behaviour. This would be theoretical interest as animal experiments show that 5-HT may be an anorectic transmitter. It is also of practical importance as then the embarrassing side effect of weight gain might be avoided in antidepressive treatment. PMID:6939316

  10. Hepatitis C virus load and expression of a unique subset of cellular genes in circulating lymphoid cells differentiate non-responders from responders to pegylated interferon alpha-ribavirin treatment.

    PubMed

    Pham, Tram N Q; Lin, Dolly M H; Mulrooney-Cousins, Patricia M; Churchill, Norma D; Kowala-Piaskowska, Arleta; Mozer-Lisewska, Iwona; Machaj, Anna; Pazgan-Simon, Monika; Zalewska, Malgorzata; Simon, Krzysztof; King, Dawn; Reddy, S Bharati; Michalak, Tomasz I

    2013-03-01

    Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies. PMID:23280583

  11. Citalopram versus other anti-depressive agents for depression

    PubMed Central

    Cipriani, Andrea; Purgato, Marianna; Furukawa, Toshi A; Trespidi, Carlotta; Imperadore, Giuseppe; Signoretti, Alessandra; Churchill, Rachel; Watanabe, Norio; Barbui, Corrado

    2014-01-01

    Background Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode. Systematic reviews have already highlighted some differences in efficacy between second-generation antidepressants. Citalopram, one of the first selective serotonin reuptake inhibitors (SSRI) introduced in the market, is one of these antidepressant drugs that clinicians use for routine depression care. Objectives To assess the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with tricyclics, heterocyclics, other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression. Search methods We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to February 2012. No language restriction was applied. We contacted pharmaceutical companies and experts in this field for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to citalopram versus any other antidepressants. Data collection and analysis Two reviewers independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), patient acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results Thirty-seven trials compared citalopram with other antidepressants (such as tricyclics, heterocyclics, SSRIs and other antidepressants, either conventional ones, such as mirtazapine, venlafaxine and reboxetine, or non-conventional, like hypericum). Citalopram was shown to be significantly less effective than escitalopram in achieving acute response (odds

  12. Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers.

    PubMed

    Milrod, Barbara; Altemus, Margaret; Gross, Charles; Busch, Fredric; Silver, Gabrielle; Christos, Paul; Stieber, Joshua; Schneier, Franklin

    2016-04-01

    Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to

  13. Electrochemical Synthesis and Kinetic Evaluation of Electrooxidation of Acetaminophen in the Presence of Antidepressant Drugs

    PubMed Central

    Nematollahi, Davood; Feyzi Barnaji, Bahareh; Amani, Ameneh

    2015-01-01

    With the aim of obtaining information about drug-drug interaction (DDI) between acetaminophen and some of antidepressant drugs (fluoxetine, sertraline and nortriptyline), in the present work we studied the electrochemical oxidation of acetaminophen (paracetamol) in the presence of these drugs by means of cyclic voltammetry and Controlled-potential coulometry. The reaction between N-acetyl-p-benzoquinone-imine (NAPQI) produced from electrooxidation of acetaminophen and antidepressant drugs (see scheme 1) cause to reduce the concentration of NAPQI and decreases the effective concentration of antidepressants. The cyclic voltammetric data were analyzed by digital simulation to measure the homogeneous parameters for the suggesting electrode mechanism. The calculated observed homogeneous rate constants (kobs) for the reaction of electrochemically generated N-acetyl-para benzoquinn-imine with antidepressant drugs was found to vary in the order kobsnortriptyline > kobssertraline > kobsfluxetine at biological pH. PMID:26664378

  14. Anti-anxiety and anti-depressant activities of Sarasvata choorna in experimental animals

    PubMed Central

    Gupta, Kshama; Ashok, B. K.; Ravishankar, B.; Thakar, A. B.

    2011-01-01

    The present study was undertaken to evaluate the anxiolytic and anti-depressant activity of Sarasvata choorna. The anxiolytic activity was evaluated in elevated plus maze (EPM) and the anti-depressant activity was evaluated in forced swimming test (FST). The efficacy of Sarasvata choorna was compared with the standard anti-anxiety (diazepam 2 mg/kg) and anti-depressant (imipramine – 5 mg/kg) drugs. It was observed that Sarasvata choorna at the dose of 390 mg/kg is as effective as standard drugs used in anti-anxiety and anti-depressant activities in mice by increasing time spent in open arm and entries to open arm in EPM model and increasing immobility time in FST model respectively. Hence it can be concluded that Sarasvata choorna may be used as a potent therapeutic agent in treating anxiety and depressive disorders. PMID:22661860

  15. Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine

    PubMed Central

    Walayat, Saqib; Ahmed, Zohair; Martin, Daniel; Puli, Srinivas; Cashman, Michael; Dhillon, Sonu

    2015-01-01

    Hepatitis B virus (HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed non-responders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated. PMID:26523203

  16. Constraints of nonresponding flows based on cross layers in the networks

    NASA Astrophysics Data System (ADS)

    Zhou, Zhi-Chao; Xiao, Yang; Wang, Dong

    2016-02-01

    In the active queue management (AQM) scheme, core routers cannot manage and constrain user datagram protocol (UDP) data flows by the sliding window control mechanism in the transport layer due to the nonresponsive nature of such traffic flows. However, the UDP traffics occupy a large part of the network service nowadays which brings a great challenge to the stability of the more and more complex networks. To solve the uncontrollable problem, this paper proposes a cross layers random early detection (CLRED) scheme, which can control the nonresponding UDP-like flows rate effectively when congestion occurs in the access point (AP). The CLRED makes use of the MAC frame acknowledgement (ACK) transmitting congestion information to the sources nodes and utilizes the back-off windows of the MAC layer throttling data rate. Consequently, the UDP-like flows data rate can be restrained timely by the sources nodes in order to alleviate congestion in the complex networks. The proposed CLRED can constrain the nonresponsive flows availably and make the communication expedite, so that the network can sustain stable. The simulation results of network simulator-2 (NS2) verify the proposed CLRED scheme.

  17. Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects

    PubMed Central

    Jutkiewicz, Emily M.; Torregrossa, Mary M.; Sobczyk-Kojiro, Katarzyna; Mosberg, Henry I.; Folk, John E.; Rice, Kenner C.; Watson, Stanley J.; Woods, James H.

    2007-01-01

    Nonpeptidic delta-opioid receptor agonists produce antidepressant-like effects in rodents, and compounds that inhibit the breakdown of endogenous opioid peptides have antidepressant-like effects in animal models. In this study, the behavioral effects of the enkephalinase inhibitor, RB101 (N-[(R, S)-2-benzyl-3-[(S)(2-amino-4-methyl-thio)-butyldithio]-1-oxopropyl]-l-phenylalanine benzyl ester), were examined. Specifically, the effects of RB101 on convulsive activity, locomotor activity, and antidepressant-like effects in the forced swim test were studied in Sprague–Dawley rats, and the opioid receptor types mediating these effects were examined by antagonist studies. In addition, the effects of RB101 on brain-derived neurotrophic factor (BDNF) mRNA expression were evaluated in relation to its antidepressant effects. RB101 produced delta-opioid receptor-mediated antidepressant effects (32 mg/kg i.v. and 100 mg/kg i.p.) and increased locomotor activity (32 mg/kg i.v.) in rats. RB101 did not produce convulsions or seizures and did not alter BDNF mRNA expression. In conclusion, RB101 has the potential to produce antidepressant effects without convulsions. PMID:16442521

  18. Duloxetine versus other anti-depressive agents for depression

    PubMed Central

    Cipriani, Andrea; Koesters, Markus; Furukawa, Toshi A; Nosè, Michela; Purgato, Marianna; Omori, Ichiro M; Trespidi, Carlotta; Barbui, Corrado

    2014-01-01

    Background Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. Objectives To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. Main results A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies

  19. Instant and Persistent Antidepressant Response of Gardenia Yellow Pigment Is Associated with Acute Protein Synthesis and Delayed Upregulation of BDNF Expression in the Hippocampus.

    PubMed

    Wu, Ruyan; Tao, Weiwei; Zhang, Hailou; Xue, Wenda; Zou, Zhilu; Wu, Haoxin; Cai, Baochang; Doron, Ravid; Chen, Gang

    2016-08-17

    Gardenia yellow pigment (GYP) is a collection of compounds with shared structure of crocin, which confers antidepressant activity. GYP is remarkably enriched in Gardenia jasminoides Ellis, implicated in rapid antidepressant effects that are exerted through enhanced neuroplasticity. This study aims to investigate the rapid antidepressant-like activity of GYP and its underlying mechanism. After the optimal dose was determined, antidepressant responses in tail suspension test or forced swim test were monitored at 30 min, 1 day, 3 days, and 7 days post a single GYP administration. Rapid antidepressant potential was tested using learned helplessness paradigm. The expression of proteins involved in hippocampal neuroplasticity was determined. The effect of blockade of protein synthesis on GYP's antidepressant response was examined. Antidepressant response was detected at 30 min, and lasted for at least 3 days post a single administration of GYP. A single administration of GYP also reversed the deficits in learned helplessness test. Thirty minutes post GYP administration, ERK signaling was activated, and its downstream effector phosphorylated eukaryotic elongation factor 2 was inhibited, contributing to increased protein translation. Expression of synaptic proteins GluR1 and synapsin 1 was upregulated. Blockade of protein synthesis with anisomycin blunted the immediate antidepressant response of GYP. CREB signaling and BDNF expression were upregulated at 24 h, but not at 30 min. In conclusion, GYP-induced immediate antidepressant response was dependent on synthesis of proteins, including synaptic proteins. This was followed by enhanced expression of CREB and BDNF, which likely mediated the persistent antidepressant responses. PMID:27203575

  20. Antidepressant therapy in the chronic fatigue syndrome.

    PubMed Central

    Lynch, S; Seth, R; Montgomery, S

    1991-01-01

    The chronic fatigue syndrome is a condition receiving increasing recognition. Symptoms of depression are not infrequent and may be persistent and severe enough to warrant treatment. The controversy over the use of antidepressant therapy in this condition may present a dilemma for the general practitioner considering possible treatments. This paper draws on the literature and on the authors' own observations of patients with the chronic fatigue syndrome to suggest guidelines for the use of antidepressant therapy. PMID:1822108

  1. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    USGS Publications Warehouse

    Schultz, M.M.; Painter, M.M.; Bartell, S.E.; Logue, A.; Furlong, E.T.; Werner, S.L.; Schoenfuss, H.L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305. ng/L and 1104. ng/L) and SER (5.2. ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28. ng/L induced vitellogenin in male fish-a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies. ?? 2011 Elsevier B.V.

  2. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    USGS Publications Warehouse

    Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

  3. Predictors of Start of Different Antidepressants in Patient Charts among Patients with Depression

    PubMed Central

    Kim, Hyungjin Myra; Zivin, Kara; Choe, Hae Mi; Stano, Clare M.; Ganoczy, Dara; Walters, Heather; Valenstein, Marcia

    2016-01-01

    Background In usual psychiatric care, antidepressant treatments are selected based on physician and patient preferences rather than being randomly allocated, resulting in spurious associations between these treatments and outcome studies. Objectives To identify factors recorded in electronic medical chart progress notes predictive of antidepressant selection among patients who had received a depression diagnosis. Methods This retrospective study sample consisted of 556 randomly selected Veterans Health Administration (VHA) patients diagnosed with depression from April 1, 1999 to September 30, 2004, stratified by the antidepressant agent, geographic region, gender, and year of depression cohort entry. Predictors were obtained from administrative data, and additional variables were abstracted from electronic medical chart notes in the year prior to the start of the antidepressant in five categories: clinical symptoms and diagnoses, substance use, life stressors, behavioral/ideation measures (e.g., suicide attempts), and treatments received. Multinomial logistic regression analysis was used to assess the predictors associated with different antidepressant prescribing, and adjusted relative risk ratios (RRR) are reported. Results Of the administrative data-based variables, gender, age, illicit drug abuse or dependence, and number of psychiatric medications in prior year were significantly associated with antidepressant selection. After adjusting for administrative data-based variables, sleep problems (RRR = 2.47) or marital issues (RRR = 2.64) identified in the charts were significantly associated with prescribing mirtazapine rather than sertraline; however, no other chart-based variables showed a significant association or an association with a large magnitude. Conclusion Some chart data-based variables were predictive of antidepressant selection, but we neither found many nor found them highly predictive of antidepressant selection in patients treated for depression

  4. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows.

    PubMed

    Schultz, Melissa M; Painter, Meghan M; Bartell, Stephen E; Logue, Amanda; Furlong, Edward T; Werner, Stephen L; Schoenfuss, Heiko L

    2011-07-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish--a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies. PMID:21536011

  5. Attitudes and beliefs of patients with chronic depression toward antidepressants and depression

    PubMed Central

    Jacob, Sabrina Anne; Ab Rahman, Ab Fatah; Hassali, Mohamed Azmi Ahmad

    2015-01-01

    Background Many patients have erroneous views with regard to depression and its management, and it was noted that these attitudes and beliefs significantly affected their adherence rates. Objectives The primary aim of this study was to determine the attitudes and beliefs of patients with depression toward depression and antidepressants. A secondary aim was to assess the influence of ethnicity on patients’ attitudes and beliefs. Patients and methods The study involved patients with chronic depression being followed up at an outpatient clinic at a government-run hospital in Malaysia. Patients’ attitudes and beliefs were assessed using the Antidepressant Compliance Questionnaire. Results A total of 104 patients of Malay, Chinese, and Indian ethnic groups met the selection criteria. Chinese patients had significantly negative attitudes and beliefs toward depression and antidepressants compared to Malays and Indians (b=-8.96, t103=-3.22; P<0.05). Component analysis revealed that 59% of patients believed that antidepressants can cause a person to have less control over their thoughts and feelings, while 67% believed that antidepressants could alter one’s personality; 60% believed it was okay to take fewer tablets on days when they felt better, while 66% believed that antidepressants helped solve their emotional problems and helped them worry less. Conclusion Patients had an overall positive view as to the benefits of antidepressants, but the majority had incorrect views as to the acceptable dosing of antidepressants and had concerns about the safety of the medication. Assessing patients’ attitudes and beliefs, as well as the impact of their respective cultures, can be used in tailoring psychoeducation sessions accordingly. PMID:26064052

  6. Issues encountered in recent attempts to develop novel antidepressant agents.

    PubMed

    Schatzberg, Alan F

    2015-05-01

    The development of new antidepressants has had mixed results over the past decade, with several notable failures. This paper reviews a number of major initiatives in the development of new antidepressant agents. Traditional strategies to build on agents that have monoaminergic effects at the synapse (e.g., vilazodone and ketamine) have been complemented with efforts that have emphasized devices and brain circuits (e.g., deep brain stimulation and transcranial magnetic stimulation) or chemical agents that modulate neuroendocrine systems (e.g., glucocorticoid antagonists, mixed melatonin agonists/serotonin type-2 receptor antagonists). Interestingly, chemical agents, such as onabotulinumtoxin A, may affect brain circuits as well. We present data from recent studies in drug and device development--reviewing progress made, stumbling blocks encountered, and issues that need to be addressed in future studies. PMID:25762133

  7. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    PubMed Central

    Xue, Wenda; Zhou, Xin; Yi, Nan; Jiang, Lihua; Tao, Weiwei; Wu, Runjie; Wang, Dan; Jiang, Jingjing; Ge, Xiaoyin; Wang, Yuyue; Wu, Haoxin; Chen, Gang

    2013-01-01

    The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2), leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression. PMID:23710213

  8. Novel sigma (σ) receptor agonists produce antidepressant-like effects in mice

    PubMed Central

    Wang, Jiajia; Mack, Aisha L.; Coop, Andrew; Matsumoto, Rae R.

    2014-01-01

    Many antidepressant drugs interact with σ receptors and accumulating evidence suggests that these proteins mediate antidepressant-like effects in animals and humans. σ Receptors are localized in brain regions affected in depression, further strengthening the hypothesis that they represent logical drug development targets. In this study, two novel σ receptor agonists (UMB23, UMB82) were evaluated for antidepressant-like activity in mice. First, radioligand binding studies confirmed that the novel compounds had preferential affinity for σ receptors. Second, the forced swim test, a well established animal model for screening potential antidepressant drugs, showed that both compounds dose-dependently reduced immobility time. The σ receptor antagonist BD1047 attenuated the antidepressant-like effects of UMB23 and UMB82. Third, locomotor activity suggested that the effects of UMB23 and UMB82 in the forced swim test were not due to non-specific motor activating effects. Together, the data provide further evidence that σ receptor agonists represent a possible new class of antidepressant medication. PMID:17376658

  9. Caffeine enhances the antidepressant-like activity of common antidepressant drugs in the forced swim test in mice.

    PubMed

    Szopa, Aleksandra; Poleszak, Ewa; Wyska, Elżbieta; Serefko, Anna; Wośko, Sylwia; Wlaź, Aleksandra; Pieróg, Mateusz; Wróbel, Andrzej; Wlaź, Piotr

    2016-02-01

    Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through adenosine receptors. Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. The main goal of the present study was to evaluate the influence of caffeine on animals' behavior in forced swim test (FST) as well as the effect of caffeine (5 mg/kg) on the activity of six typical antidepressants, such as imipramine (15 mg/kg), desipramine (10 mg/kg), fluoxetine (5 mg/kg), paroxetine (0.5 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of caffeine on the levels of antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that caffeine at a dose of 10, 20, and 50 mg/kg exhibited antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals. Caffeine at a dose of 5 mg/kg potentiated the activity of all antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between caffeine and desipramine, fluoxetine, escitalopram, and reboxetine were exclusively of pharmacodynamic character, because caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of caffeine and paroxetine, an increase in the antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the antidepressant drug concentrations in brain was observed in the case of imipramine administered together with caffeine. Therefore, it can be assumed that the interactions caffeine-paroxetine and caffeine-imipramine occur at least in

  10. An electronic health record driven algorithm to identify incident antidepressant medication users

    PubMed Central

    Bobo, William V; Pathak, Jyotishman; Kremers, Hilal Maradit; Yawn, Barbara P; Brue, Scott M; Stoppel, Cynthia J; Croarkin, Paul E; St Sauver, Jennifer; Frye, Mark A; Rocca, Walter A

    2014-01-01

    Objective We validated an algorithm designed to identify new or prevalent users of antidepressant medications via population-based drug prescription records. Patients and methods We obtained population-based drug prescription records for the entire Olmsted County, Minnesota, population from 2011 to 2012 (N=149 629) using the existing electronic medical records linkage infrastructure of the Rochester Epidemiology Project (REP). We selected electronically a random sample of 200 new antidepressant users stratified by age and sex. The algorithm required the exclusion of antidepressant use in the 6 months preceding the date of the first qualifying antidepressant prescription (index date). Medical records were manually reviewed and adjudicated to calculate the positive predictive value (PPV). We also manually reviewed the records of a random sample of 200 antihistamine users who did not meet the case definition of new antidepressant user to estimate the negative predictive value (NPV). Results 161 of the 198 subjects electronically identified as new antidepressant users were confirmed by manual record review (PPV 81.3%). Restricting the definition of new users to subjects who were prescribed typical starting doses of each agent for treating major depression in non-geriatric adults resulted in an increase in the PPV (90.9%). Extending the time windows with no antidepressant use preceding the index date resulted in only modest increases in PPV. The manual abstraction of medical records of 200 antihistamine users yielded an NPV of 98.5%. Conclusions Our study confirms that REP prescription records can be used to identify prevalent and incident users of antidepressants in the Olmsted County, Minnesota, population. PMID:24780720

  11. Patterns and Predictors of Antidepressant Use in Ambulatory Cancer Patients with Common Solid Tumors

    PubMed Central

    Fisch, Michael J.; Zhao, Fengmin; Manola, Judith; Miller, Andrew H.; Pirl, William F.; Wagner, Lynne I.

    2014-01-01

    Purpose Depressive symptoms and antidepressant use are prevalent among cancer patients. We sought to identify determinants of prescribing commonly used antidepressants. Patients and Methods This multi-institutional study enrolled 3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or lung. Five case-finding methods were used to identify patients with depressive symptoms. Logistic models were used to examine factors that impact antidepressant use. Results Approximately 47% of patients were defined as having depressive symptoms. Clinicians rated being sad/depressed as one of the top three priority problems for 10.5% of patients. Antidepressants were prescribed in 19% of all patients; 25% with depressive symptoms and 14% non-depressed patients. After adjusting for other covariates, these variable categories were significantly associated with greater use of antidepressants: depressive symptoms, family history of depression, concurrent medication use, cancer treatment status, and certain other clinical and demographic variables. The strongest individual predictors were concurrent use of more than 10 medications (odds ratio [OR] = 3.3), a family history of depression (OR = 2.2), sedative use (OR=2.1), non-Hispanic white race (OR = 2.0), and anxiolytics use (OR = 2.0). Conclusions Depressive symptoms are found in nearly half of outpatients with cancer, and one-fourth of patients with depressive symptoms are taking an antidepressant. Patients receiving antidepressants are more often those taking multiple medications, those with a depression diathesis, and those with more extensive cancer treatment. Patients who were younger, white and female were also more likely to be taking antidepressants. PMID:24930693

  12. The CYP4502D6 *4 and *6 alleles are the molecular genetic markers for drug response: implications in colchicine non-responder FMF patients.

    PubMed

    Yalcıntepe, Sinem; Ozdemır, Ozturk; Sılan, Coskun; Ozen, Filiz; Uludag, Ahmet; Candan, Ferhan; Sılan, Fatma

    2016-06-01

    The cytochrome P450 2D6 (CYP2D6) is a cytochrome P450 enzyme involved in the oxidative biotransformation of the xenobiotics, carcinogens and various clinically important drugs. Patients are evaluated in three sub-groups of extensive (EM), intermediate (IM) and poor metabolizer (PM) phenotypes due to their drug-metabolising ability for the target CYP2D6 gene. Colchicine non-responsive FMF patients were prospectively genotyped for the major CYP2D6 alleles in the current study. Major CYP2D6 alleles of *1, *3, *4, *5, and *6 were genotyped for 30 responsive and 60 non-responsive FMF patients by multiplex PCR-based reverse-hybridization StripAssay and real-time PCR methods. DNA banks isolated from blood-EDTA were retrospectively used in the current patients and results were compared statistically. Increased CYP2D6 *4 and *6 allele frequencies were highly detected in the colchicine non-responsive FMF patients when compared to the responsive group. Results showed the frequencies of major CYP2D6 *1(wild), *3(2637A > delA), *4(G1934A), *5(total gene deletion) and *6(1707T del) alleles in 0.550, 0.042, 0.158, 0.025 and 0.225 for non-responder and 0.880 and 0.120 (CYP2D6*1 and *4) for the responder groups, respectively. Despite small sample size, this study suggests that there is an association between CYP2D6*4 and CYP2D6*6 alleles and drug intoxicants in colchicine non-responder FMF patients. PMID:25645282

  13. The Antidepressant-like Effects of Estrogen-mediated Ghrelin

    PubMed Central

    Wang, Pu; Liu, Changhong; Liu, Lei; Zhang, Xingyi; Ren, Bingzhong; Li, Bingjin

    2015-01-01

    Ghrelin, one of the brain-gut peptides, stimulates food-intake. Recently, ghrelin has also shown to play an important role in depression treatment. However, the mechanism of ghrelin’s antidepressant-like actions is unknown. On the other hand, sex differences in depression, and the fluctuation of estrogens secretion have been proved to play a key role in depression. It has been reported that women have higher level of ghrelin expression, and ghrelin can stimulate estrogen secretion while estrogen acts as a positive feedback mechanism to up-regulate ghrelin level. Ghrelin may be a potential regulator of reproductive function, and estrogen may have additional effect in ghrelin’s antidepressantlike actions. In this review, we summarize antidepressant-like effects of ghrelin and estrogen in basic and clinical studies, and provide new insight on ghrelin’s effect in depression. PMID:26412072

  14. Negotiating the neurochemical self: anti-depressant consumption in women's recovery from depression.

    PubMed

    Fullagar, Simone

    2009-07-01

    Anti-depressant treatment can be viewed as an exercise of biopower that is articulated through policies and practices aimed at the reduction of depression, population healthcare costs and effects on labour force productivity. Drawing upon a feminist governmentality perspective, this article examines the discourses that shaped women's experiences of anti-depressant medication in an Australian qualitative study on recovery from depression. The majority of women had been prescribed anti-depressants to treat a chemical imbalance in the brain, manage symptoms and restore normal functioning. One-third of participants identified anti-depressants as helpful in their recovery, while two-thirds were either highly ambivalent about, or critical of, medication as a solution to depression. Thirty-one women who identified the ;positive' benefits of anti-depressants actively constituted themselves as biomedical consumers seeking to redress a chemical imbalance. The problem of depression, the emergence of molecular science and the push for pharmacological solutions are contributing to the discursive formation of new subject positions - such as the neurochemically deficient self. Three themes were identified in relation to medication use, namely restoring normality, signifying recovery success and control/uncertainty. Anti-depressant medication offered women a normalized pathway to successful recovery that stood in stark contrast to the biologically deficient and morally failing self. These women's stories importantly reveal the gender relations and paradoxes arising from biopolitical technologies that shape selfhood for women in advanced liberal societies. PMID:19491233

  15. "My dirty little habit": Patient constructions of antidepressant use and the 'crisis' of legitimacy.

    PubMed

    Ridge, Damien; Kokanovic, Renata; Broom, Alex; Kirkpatrick, Susan; Anderson, Claire; Tanner, Claire

    2015-12-01

    Discontents surrounding depression are many, and include concerns about a creeping appropriation of everyday kinds of misery; divergent opinions on the diagnostic category(ies); and debates about causes and appropriate treatments. The somewhat mixed fortunes of antidepressants - including concerns about their efficacy, overuse and impacts on personhood - have contributed to a moral ambivalence around antidepressant use for people with mental health issues. Given this, we set out to critically examine how antidepressant users engage in the moral underpinnings of their use, especially how they ascribe legitimacy (or otherwise) to this usage. Using a modified constant comparative approach, we analyzed 107 narrative interviews (32 in UKa, 36 in UKb, 39 in Australia) collected in three research studies of experiences of depression in the UK (2003-4 UKa, and 2012 UKb) and in Australia (2010-11). We contend that with the precariousness of the legitimacy of the pharmaceutical treatment of depression, participants embark on their own legitimization work, often alone and while distressed. We posit that here, individuals with depression may be particularly susceptible to moral uncertainty about their illness and pharmaceutical interventions, including concerns about shameful antidepressant use and deviance (e.g. conceiving medication as pseudo-illicit). We conclude that while people's experiences of antidepressants (including successful treatments) involve challenges to illegitimacy narratives, it is difficult for participants to escape the influence of underlying moral concerns, and the legitimacy quandary powerfully shapes antidepressant use. PMID:26498732

  16. A review of the management of antidepressant discontinuation symptoms

    PubMed Central

    Wilson, Emma; Lader, Malcolm

    2015-01-01

    Strong evidence supports the existence of a discontinuation syndrome following the withdrawal of antidepressant medication, particularly second-generation antidepressants. The syndrome is a common phenomenon and guidance as to best avoid the symptoms is essential for both practitioners and patients. The current study reviewed the available literature on the best methods of discontinuation for antidepressants in order to avoid or prevent the occurrence of any unpleasant side effects associated with antidepressant withdrawal. Accordingly, an electronic search of the PubMed/MedLine database and Google Scholar was conducted to find relevant literature published within the last 10 years. From this, 18 related articles were identified; five clinical studies, one case series, one consensus panel’s recommendations and 11 literature reviews. Of the articles reviewed there is a general consensus as to tapering the drug slowly over a period of weeks or months. Also, in those patients who experience severe symptoms the drug should be reinstated and discontinued more gradually. The discontinuation syndrome does not occur as frequently or severely with longer-acting agents such as fluoxetine and therefore it is recommended that switching to this drug prior to withdrawal may be advisable. The articles reviewed also emphasize the need for patient education and reassurance throughout the discontinuation process. One in particular adds that cognitive behavioural therapy may be a useful tool in easing the patients’ distress. However, this review highlights the lack of controlled data to support the available guidelines. Furthermore, the guidance which is available is somewhat conflicting. Research approaches should address this issue as well as develop appropriate methods of withdrawal for specific drugs. PMID:26834969

  17. Effects of antidepressants on P2X7 receptors.

    PubMed

    Wang, Wei; Xiang, Zheng-Hua; Jiang, Chun-Lei; Liu, Wei-Zhi; Shang, Zhi-Lei

    2016-08-30

    Antidepressants including paroxetine, fluoxetine and desipramine are commonly used for treating depression. P2×7 receptors are member of the P2X family. Recent studies indicate that these receptors may constitute a novel potential target for the treatment of depression. In the present study, we examined the action of these antidepressants on cloned rat P2×7 receptors that were stably expressed in human embryonic kidney (HEK) 293 cells by using the whole-cell patch-clamp technique, and found that paroxetine at a dose of 10µM could significantly reduce the inward currents evoked by the P2×7 receptors agonist BzATP by pre-incubation for 6-12 but not by acute application (10µM) or pre-incubation for 2-6h at a dose of 1µM, 3µM or 10µM paroxetine. Neither fluoxetine nor desipramine had significant effects on currents evoked by BzATP either applied acutely or by pre-incubation at various concentrations. These results suggest that the sensitivity of rat P2×7 receptors to antidepressants is different, which may represent an unknown mechanism by which these drugs exert their therapeutic effects and side effects. PMID:27318632

  18. Antidepressants, anxiolytics, and hypnotics in pregnancy and lactation

    PubMed Central

    Ram, Daya; Gandotra, S.

    2015-01-01

    Aims: Untreated perinatal depression and anxiety disorders are known to have significant negative impact on both maternal and fetal health. Dilemmas still remain regarding the use and safety of psychotropics in pregnant and lactating women suffering from perinatal depression and anxiety disorders. The aim of the current paper was to review the existing evidence base on the exposure and consequences of antidepressants, anxiolytics, and hypnotics in women during pregnancy and lactation and to make recommendations for clinical decision making in management of these cases. Materials and Methods: We undertook a bibliographic search of Medline/PubMed (1972 through 2014), Science Direct (1972 through 2014), Archives of Indian Journal of Psychiatry databases was done. References of retrieved articles, reference books, and dedicated websites were also checked. Results and Conclusions: The existing evidence base is extensive in studying multiple outcomes of the antidepressant or anxiolytic exposure in neonates, and some of the findings appear conflicting. Selective serotonin reuptake inhibitors are the most researched antidepressants in pregnancy and lactation. The available literature is criticized mostly on the lack of rigorous well designed controlled studies as well as lacunae in the methodologies, interpretation of statistical information, knowledge transfer, and translation of information. Research in this area in the Indian context is strikingly scarce. Appropriate risk-benefit analysis of untreated mental illness versus medication exposure, tailor-made to each patient's past response and preference within in the context of the available evidence should guide clinical decision making. PMID:26330654

  19. The role of 5-HT1A receptors in mediating acute negative effects of antidepressants: implications in pediatric depression.

    PubMed

    Rahn, K A; Cao, Y-J; Hendrix, C W; Kaplin, A I

    2015-01-01

    Acute antidepressant exposure elevates the frequency of impulsive behavior and suicidal thoughts in children and adolescents with major depressive disorder (MDD). Long-term antidepressant treatment, however, is beneficial for pediatric MDD, so it is necessary to explore novel treatments that prevent the potentially dangerous consequences of acute antidepressant initiation. In the present study, a treatment strategy designed to reverse the acute negative behavioral effects of antidepressants was tested in rodents. Co-administration of the 5-HT1A receptor (5-HT1AR) antagonist WAY-100635 reversed the negative effects of acute fluoxetine, a serotonin reuptake inhibitor, but not reboxetine, a norepinephrine reuptake inhibitor, supporting the involvement of 5-HT1AR in mediating the negative consequences of acute selective serotonin reuptake inhibitor (SSRI) treatment. No 5-HT1AR antagonists are currently approved for use in pediatric populations, so alternative strategies should be explored. One such strategy was suggested based on the hypothesis that the rate of 5-HT1AR activation and the subsequent inhibition of serotonergic neuron activity caused by acute SSRI administration is proportional to the loading rate of an antidepressant. Existing pharmacological data were examined, and significant correlations were observed between the half-life of antidepressants and the rate of suicide-related events (SREs). Specifically, antidepressants with longer half-lives have lower rates of SREs. On the basis of these data, novel dosing strategies were developed for five antidepressants to mimic the pharmacological profile of the antidepressant with the longest half-life, fluoxetine. These dosing strategies could be used to decrease the rate of SREs associated with acute antidepressant treatment in pediatric MDD until an improved pharmacological treatment is developed. PMID:25942044

  20. The role of 5-HT1A receptors in mediating acute negative effects of antidepressants: implications in pediatric depression

    PubMed Central

    Rahn, K A; Cao, Y-J; Hendrix, C W; Kaplin, A I

    2015-01-01

    Acute antidepressant exposure elevates the frequency of impulsive behavior and suicidal thoughts in children and adolescents with major depressive disorder (MDD). Long-term antidepressant treatment, however, is beneficial for pediatric MDD, so it is necessary to explore novel treatments that prevent the potentially dangerous consequences of acute antidepressant initiation. In the present study, a treatment strategy designed to reverse the acute negative behavioral effects of antidepressants was tested in rodents. Co-administration of the 5-HT1A receptor (5-HT1AR) antagonist WAY-100635 reversed the negative effects of acute fluoxetine, a serotonin reuptake inhibitor, but not reboxetine, a norepinephrine reuptake inhibitor, supporting the involvement of 5-HT1AR in mediating the negative consequences of acute selective serotonin reuptake inhibitor (SSRI) treatment. No 5-HT1AR antagonists are currently approved for use in pediatric populations, so alternative strategies should be explored. One such strategy was suggested based on the hypothesis that the rate of 5-HT1AR activation and the subsequent inhibition of serotonergic neuron activity caused by acute SSRI administration is proportional to the loading rate of an antidepressant. Existing pharmacological data were examined, and significant correlations were observed between the half-life of antidepressants and the rate of suicide-related events (SREs). Specifically, antidepressants with longer half-lives have lower rates of SREs. On the basis of these data, novel dosing strategies were developed for five antidepressants to mimic the pharmacological profile of the antidepressant with the longest half-life, fluoxetine. These dosing strategies could be used to decrease the rate of SREs associated with acute antidepressant treatment in pediatric MDD until an improved pharmacological treatment is developed. PMID:25942044

  1. Translocator protein mediates the anxiolytic and antidepressant effects of midazolam.

    PubMed

    Qiu, Zhi-Kun; Li, Ming-Sheng; He, Jia-Li; Liu, Xu; Zhang, Guan-Hua; Lai, Sha; Ma, Jian-Chun; Zeng, Jia; Li, Yan; Wu, Hong-Wei; Chen, Yong; Shen, Yong-Gang; Chen, Ji-Sheng

    2015-12-01

    The translocator protein (18 kDa) (TSPO) plays an important role in stress-related disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD), caused by neurosteroids (e.g. allopregnanolone). The present study sought to evaluate the significance of TSPO in anxiolytic and antidepressant effects induced by midazolam. The animals were administrated midazolam (0.25, 0.5 and 1 mg/kg, i.p.) and subjected to behavioral tests, including Vogel-type conflict test, elevated plus-maze test, forced swimming test. Midazolam produced anxiolytic- and antidepressant-like effects Vogel-type conflict test (1 mg/kg, i.p.), elevated plus-maze test (0.5 and 1 mg/kg, i.p.), and forced swimming test (0.5 and 1 mg/kg, i.p.). These effects of Midazolam were totally blocked by the TSPO antagonist PK11195 (3 mg/kg, i.p.). To evaluate the role of allopregnanolone in the anxiolytic- and antidepressant-like effects of midazolam, the animals were decapitated at the end of the behavioral tests. The allopregnanolone levels of the prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The allopregnanolone level of the prefrontal cortex and hippocampus was increased by midazolam (0.5, 1 mg/kg, i.p.) and the increase was reversed by PK11195 (3 mg/kg, i.p.). Overall, the results indicated that the anxiolytic- and antidepressant-like effects of midazolam were mediated by TSPO, via stimulation of allopregnanolone biosynthesis. PMID:26455280

  2. Childhood and adolescent depression: why do children and adults respond differently to antidepressant drugs?

    PubMed

    Bylund, David B; Reed, Abbey L

    2007-10-01

    Childhood and adolescent depression is an increasingly problematic diagnosis for young people due to a lack of effective treatments for this age group. The symptoms of adult depression can be treated effectively with multiple classes of antidepressant drugs which have been developed over the years using animal and human studies. But many of the antidepressants used to treat adult depression cannot be used for pediatric depression because of a lack of efficacy and/or side effects. The reason that children and adolescents respond differently to antidepressant treatment than adults is poorly understood. In order to better understand the etiology of pediatric depression and treatments that are effective for this age group, the differences between adults, children and adolescents needed to be elucidated. Much of the understanding of adult depression has come from studies using adult animals, therefore studies using juvenile animals would likely help us to better understand childhood and adolescent depression. Recent studies have shown both neurochemical and behavioral differences between adult and juvenile animals after antidepressant treatment. Juvenile animals have differences compared to adult animals in the maturation of the serotonergic and noradrenergic systems, and in dose of antidepressant drug needed to achieve similar brain levels. Differences after administration of antidepressant drug have also been reported for adrenergic receptor regulation, a physiologic hypothermic response, as well as behavioral differences in two animal models of depression. The differences between adults and juveniles not only in the human response to antidepressants but also with animals studies warrant a specific distinction between the study of pediatric and adult depression and the manner in which new treatments are pursued. PMID:17664028

  3. Antidepressant use and new-onset diabetes: a systematic review and meta-analysis

    PubMed Central

    Bhattacharjee, Sandipan; Bhattacharya, Rituparna; Kelley, George A.; Sambamoorthi, Usha

    2016-01-01

    Summary Antidepressant use has been linked to new-onset diabetes. However, the existing literature on this relationship has yielded inconsistent findings. The primary objective of this study was to systematically synthesize the literature on the relationship between antidepressant use and new-onset diabetes using meta-analysis. A systematic literature search was conducted to identify relevant studies in seven electronic databases. Two independent reviewers identified the final list of studies to be included in the meta-analysis using a priori selection criteria. Results for the primary outcome of interest, that is, odds and hazards of developing new-onset diabetes, were pooled using a random-effects model. Egger’s regression test and the Trim and Fill method were utilized to detect the presence of any potential publication bias. Sensitivity analysis was conducted using the leave-one-out method as well as individual categories of antidepressant drugs. Eight studies met the inclusion criteria. Random effects models revealed that adults with any use of antidepressants were more likely to develop new-onset diabetes compared with those without any use of antidepressants [odd ratios = 1.50, 95% confidence interval (CI), 1.08–2.10; hazards ratio = 1.19, 95% CI, 1.08–1.32]. Sensitivity analyses revealed fair robustness; selective serotonin reuptake inhibitors and tricyclic antidepressants were more likely to be associated with the development of new-onset diabetes. Results from the Egger’s regression test and Trim and Fill method revealed no evidence of publication bias. Among adults, antidepressant use was associated with higher chances of new-onset diabetes. However, because a cause-and-effect relationship cannot be established by observational studies, future randomized controlled studies are needed to confirm this association. PMID:23390036

  4. Second-tier natural antidepressants: review and critique.

    PubMed

    Iovieno, Nadia; Dalton, Elizabeth D; Fava, Maurizio; Mischoulon, David

    2011-05-01

    The use of Complementary and Alternative Medicine (CAM) for physical and mental problems has increased significantly in the US over the past two decades, and depression is one of the leading indications for the use of CAM. This article reviews some of the lesser-known natural products with potential psychiatric applications that are starting to emerge with some scientific and clinical evidence and may constitute a next wave of natural antidepressants: Rhodiola rosea, chromium, 5-Hydroxytryptophan (5-HTP) and inositol. Background information, efficacy data, proposed mechanisms of action, recommended doses, side effects, and precautions are reviewed. We found some encouraging data for the use of these natural products in specific populations of depressed patients. R. rosea is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects. Chromium has a beneficial effect on eating-related atypical symptoms of depression, and may be a valuable agent in treating atypical depression and seasonal affective disorder. Inositol may be useful in the treatment of bipolar depression when combined with mood stabilizers. Evidence for the clinical efficacy of 5-HTP is also promising but still preliminary. Although more well-designed and larger controlled studies are needed before any substantive conclusions can be drawn, the available evidence is compelling and these natural products deserve further investigation as a possibly significant addition to the antidepressant armamentarium. PMID:20579741

  5. Antidepressant-like effect of Ilex paraguariensis in rats.

    PubMed

    Reis, Elizete De Moraes; Schreiner Neto, Francisco Waldomiro; Cattani, Vitória Berg; Peroza, Luis Ricardo; Busanello, Alcindo; Leal, Caroline Queiroz; Boligon, Aline Augusti; Lehmen, Tássia Fontana; Libardoni, Milena; Athayde, Margareth Linde; Fachinetto, Roselei

    2014-01-01

    In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Rats were treated for four weeks with an aqueous extract of I. paraguariensis in drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours of I. paraguariensis intake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile of I. paraguariensis extract. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis was not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract of I. paraguariensis decreases the time of immobility in rats suggesting an antidepressant-like effect. PMID:24895633

  6. Perinatal Antidepressant Use: Understanding Women’s Preferences and Concerns

    PubMed Central

    BATTLE, CYNTHIA L.; SALISBURY, AMY L.; SCHOFIELD, CASEY A.; ORTIZ-HERNANDEZ, SAMIA

    2014-01-01

    Perinatal depression is prevalent and linked with a host of adverse consequences for women and newborns. Rates of engagement in depression treatment are, however, strikingly low among pregnant and postpartum women, with the majority of affected women receiving no mental health treatment. Research indicates that perinatal women are extremely reluctant to take antidepressant medications, yet the nature of women’s concerns and treatment decisionmaking patterns have not been well documented. Developing a clearer understanding of women’s treatment preferences and behaviors may help identify solutions to the under-treatment of perinatal depression. In this mixed methods study, we conducted in-depth interviews with 61 pregnant women, approximately half of whom were experiencing clinical levels of depression. In addition to assessing psychiatric diagnoses, symptoms, and functional impairment, we conducted qualitative interviews addressing women’s preferences for depression treatment, concerns, and decision-making patterns. Consistent with prior reports, women were significantly more likely to voice a preference for non-pharmacologic depression treatments, as opposed to antidepressant medications. Many depressed women reported a great degree of uncertainty regarding how to treat their depression, and those with more severe depression symptoms were more likely to endorse decisional conflict. Analysis of qualitative comments yielded detailed information about the nature of women’s concerns and preferences related to use of antidepressant medications and other aspects of treatment engagement. We discuss findings in the context of improving patient-centered care for perinatal depression. PMID:24241498

  7. Antidepressants in long-term migraine prevention.

    PubMed

    Koch, Horst J; Jürgens, Tim P

    2009-01-01

    Migraine and depression coincide in some 20-30% of patients. Although antidepressants (namely tricyclics) are not considered as first-line prophylactic compounds in patients with migraine alone, several clinical trials support a remarkable benefit in the treatment of migraine and related headache disorders. However, treatment with one antidepressant alone often does not suffice to treat both disorders effectively. Therefore, combinations of classical antidepressants with both newer antidepressants and established prophylactic drugs (e.g. beta-adrenergic receptor antagonists [beta-blockers], topiramate and sodium valproate) are required. In addition, acute attack medication (such as triptans, ergotamines or analgesics) is regularly combined with the preventive medication, thus requiring elaborate knowledge about the complex network of potential interactions and contraindications. Fear of potentially serious interactions can frequently lead to insufficient treatment of both underlying disorders, with an enormous impact on the patient's life. Pathophysiologically, multiple neurotransmitters have been attributed an important role in the aetiology of migraine (mainly serotonin and calcitonin gene-related peptide) and depression (among others, serotonin, dopamine and noradrenaline [norepinephrine]). Most drugs used to treat both disorders influence at least one of these transmitter systems, such as classical tricyclics. This review discusses the efficacy of antidepressants in migraine prevention. In addition, recommended combinations in patients with concomitant depression and migraine are presented with regard to their proposed pharmacological mechanism of action and their potential interactions. PMID:19192933

  8. Fluvoxamine versus other anti-depressive agents for depression

    PubMed Central

    Omori, Ichiro M; Watanabe, Norio; Nakagawa, Atsuo; Cipriani, Andrea; Barbui, Corrado; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

    2014-01-01

    Background Fluvoxamine, one of the oldest selective serotonin reuptake inhibitors (SSRIs), is prescribed to patients with major depression in many countries. Several studies have previously reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are now outdated. Objectives Our objective is to evaluate the effectiveness, tolerability and side effect profile of fluvoxamine for major depression in comparison with other anti-depressive agents, including tricyclics (TCAs), heterocyclics, other SSRIs, SNRIs, other newer agents and other conventional psychotropic drugs. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register. Trial databases and ongoing trial registers in North America, Europe, Japan and Australia, were handsearched for randomised controlled trials. We checked reference lists of the articles included in the review, previous systematic reviews and major textbooks of affective disorder for published reports and citations of unpublished research. The date of last search was 31 August 2008. Selection criteria We included all randomised controlled trials, published in any language, that compared fluvoxamine with any other active antidepressants in the acute phase treatment of major depression. Data collection and analysis Two independent review authors inspected citations and abstracts, obtained papers, extracted data and assessed the risk of bias of included studies. We analysed dichotomous data using odds ratios (ORs) and continuous data using the standardised mean difference (SMD). A random effects model was used to combine studies. Main results A total of 54 randomised controlled trials (n = 5122) were included. No strong evidence was found to indicate that fluvoxamine was either superior or inferior to other antidepressants regarding response, remission and tolerability. However, differing side effect profiles were evident, especially

  9. Depression, antidepressant medications, and risk of Clostridium difficile infection

    PubMed Central

    2013-01-01

    Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI. PMID:23647647

  10. [Effects of antidepressants in different populations].

    PubMed

    Vartanian, F E

    1984-01-01

    A total of 370 patients were subjected to a comprehensive international examination (within the frameworks of the WHO) by the double blind method for the efficacy of low (75 mg/day) and high (150 mg/day) doses of antidepressants (maprotiline, amitriptyline, imipramine). In 324 patients, the time course of the psychopathological disorders and side effects was studied with the aid of special scales and maps. The selection of the population and, therefore, the selection of the 7 cooperative WHO centers was based on the necessity of the maximal coverage of possible cultural, economic and ethnic relations in the patients' populations. Analysis of the total appraised ratios obtained in the course of 3 examinations of the patients has shown definite differences in the efficacy of high and low doses of the drugs under study. The data obtained indicate that the therapeutic response was equal whatever the dose (in the developing and Asian countries). In the developed countries, high doses of the drugs were found to be more effective than low ones. PMID:6705901

  11. Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects

    MedlinePlus

    ... gov/medlineplus/news/fullstory_158505.html Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects Data from ... TUESDAY, April 26, 2016 (HealthDay News) -- Omega-3 fish oil supplements may improve the effectiveness of antidepressants, ...

  12. Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects

    MedlinePlus

    ... gov/news/fullstory_158505.html Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects Data from 8 ... April 26, 2016 (HealthDay News) -- Omega-3 fish oil supplements may improve the effectiveness of antidepressants, new ...

  13. Modulatory Effects of Antidepressant Classes on the Innate and Adaptive Immune System in Depression.

    PubMed

    Eyre, H A; Lavretsky, H; Kartika, J; Qassim, A; Baune, B T

    2016-05-01

    Current reviews exploring for unique immune-modulatory profiles of antidepressant classes are limited by focusing mainly on cytokine modulation only and neglecting other aspects of the innate and adaptive immune system. These reviews also do not include recent comparative clinical trials, immune-genetic studies and therapeutics with unique neurotransmitter profiles (e. g., agomelatine). This systematic review extends the established literature by comprehensively reviewing the effects of antidepressants classes on both the innate and adaptive immune system. Antidepressants appear, in general, to reduce pro-inflammatory factor levels, particularly C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. We caution against conclusions as to which antidepressant possesses the greater anti-inflammatory effect, given the methodological heterogeneity among studies and the small number of comparative studies. The effects of antidepressant classes on adaptive immune factors are complex and poorly understood, and few studies have been conducted. Methodological heterogeneity is high among these studies (e. g., length of study, cohort characteristics, dosage used and immune marker analysis). We recommend larger, comparative studies - in clinical and pre-clinical populations. PMID:26951496

  14. The influence of multilevel upper airway surgery on CPAP tolerance in non-responders to obstructive sleep apnea surgery.

    PubMed

    Azbay, Sule; Bostanci, Asli; Aysun, Yasin; Turhan, Murat

    2016-09-01

    The aim of this study was to evaluate the influence of multilevel upper airway surgery on subsequent continuous positive airway pressure (CPAP) use and tolerance in patients with moderate to severe obstructive sleep apnea (OSA). The study cohort enrolled 67 consecutive patients, who underwent septoplasty plus modified uvulopharyngopalatoplasty (mUPPP) with or without modified tongue base suspension (mTBS) due to CPAP intolerance, and who had residual OSA requiring CPAP therapy [non-responders to surgery, apnea-hypopnea index (AHI) >15 events/h] that had been confirmed by control polysomnography at the sixth month postoperatively. A questionnaire including questions on postoperative CPAP use, problems faced during CPAP use after the surgery, change in OSA symptoms, and satisfaction with the surgery was designed, and filled through interviews. Seventeen (25.4 %) patients had septoplasty plus mUPPP and 50 (74.6 %) had septoplasty plus mUPPP combined with mTBS. Postoperatively, mean AHI (45.00 ± 19.76 vs. 36.60 ± 18.34), Epworth sleepiness scale (ESS) score (18.00 ± 4.45 vs. 13.00 ± 4.72), oxygen desaturation index (ODI) (48.98 ± 16.73 vs. 37.81 ± 17.03), and optimal CPAP level (11.80 ± 1.40 vs. 8.96 ± 1.20) were decreased (p < 0.001 for all parameters). Fifty-nine percent of patients reported that they fairly satisfied with the surgery and 49.2 % reported that their symptoms were completely resolved. While none of the cases could tolerate CPAP before surgery, almost half (47.8 %) of the cases used CPAP without problems postoperatively. Postoperative CPAP users had significantly higher postoperative AHI (p = 0.001), supine AHI (p = 0.009), ESS (p = 0.019), and ODI (p = 0.014), and significantly lower postoperative minimum O2 saturation (p = 0.001) compared with non-users. Multilevel upper airway surgery with less invasive techniques may improve CPAP tolerance in well-selected patients. PMID:26714802

  15. Orchiectomy modifies the antidepressant-like response of nicotine in the forced swimming test.

    PubMed

    Bonilla-Jaime, H; Limón-Morales, O; Arteaga-Silva, M; Hernández-González, M; Guadarrama-Cruz, G; Alarcón-Aguilar, F; Vázquez-Palacios, G

    2010-11-01

    Several studies have demonstrated that nicotine (NIC) exhibits antidepressant-like effects. In addition, it has been suggested that sexual hormones participate in the antidepressant actions of antidepressives. The present study was designed to analyze the effect of orchiectomy and the supplementation of testosterone propionate (TP) or 17β-estradiol (E(2)) on the antidepressant properties of NIC using the forced swimming test (FST), as well as to determine possible changes in the FST during different time periods after orchiectomy. In order to evaluate the influences of orchiectomy on the effects of NIC, the study first evaluated the effects of different time periods on orchiectomized rats (15, 21, 30, 45 and 60 days) that were subjected to the FST. Then, different doses of NIC (0.2, 0.4, 0.8, 1.6 mg/kg, sc) were administered for 14 days to both intact and orchiectomized rats (after 21 day) which were then also subjected to the FST. Finally, the influence of the TP or E(2) supplementation on the antidepressant-like effect of NIC on orchiectomized rats (after 21 days) was also analyzed. Results reveal that orchiectomy significantly increased immobility behavior and decreased swimming and climbing up to 60 days after castration. In contrast, NIC decreased immobility behavior and increased swimming in intact rats; whereas orchiectomy suppressed this antidepressant effect of NIC. Only with E(2) supplementation was it possible to restore the sensitivity of the castrated rats to NIC. These results suggest that E(2) was able to facilitate the antidepressant response of NIC in orchiectomized rats. PMID:20709090

  16. Prevalence and factors associated with off-label antidepressant prescriptions for insomnia

    PubMed Central

    Lai, L Leanne; Tan, Mooi Heong; Lai, Yen Chi

    2011-01-01

    Background: The primary objective of our study was to investigate the prevalence of off-label antidepressant drug use in insomnia. The secondary objective was to compare prescribing patterns between off-label antidepressants vs hypnotics approved by the US Food and Drug Administration for insomnia, with particular emphasis on socioeconomic characteristics of patients and physicians. Methods: We undertook a secondary data analysis using the national longitudinal database from the 2006 National Ambulatory Medical Care Survey. Subjects were identified from outpatient visits in which at least one insomnia drug was prescribed. A series of weighted Chi-squared statistics was used to compare drug use for insomnia across various patient and physician characteristics. Multivariate logistic regression was conducted to identify factors associated with off-label antidepressant drug use. Results: Among 901.95 million outpatient visits that took place in the US in 2006, an estimated 30.43 million visits included at least one drug prescription for insomnia. Off-label antidepressants were prescribed significantly more frequently (45.1%) than nonbenzodiazepine z-hypnotics (43.2%) and benzodiazepines (11.7%). Insomnia prescribing patterns were significantly influenced by physician specialty and physician office settings. Pediatricians (odds ratio [OR]: 65.892; 95% confidence interval [CI]: 5.536–810.564) and neurologists (OR: 4.784; 95% CI: 2.044–11.201) were more likely to prescribe off-label antidepressants than psychiatrists. Self-paying patients were more likely to receive off-label antidepressants as treatment for insomnia than patients with private insurance (OR 2.594; 95% CI: 1.128–5.967). Conclusion: Our findings indicate significant socioeconomic disparities in the use of off-label antidepressants. Future studies might explore interventional and educational strategies to ensure well informed clinical decisions that can withstand pharmaceutical marketing strategies and

  17. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectroscopy Study

    PubMed Central

    Strzelecki, Dominik; Grzelak, Piotr; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka

    2015-01-01

    Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology. PMID:26501256

  18. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. ¹H-NMR Spectroscopy Study.

    PubMed

    Strzelecki, Dominik; Grzelak, Piotr; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka

    2015-01-01

    Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (¹H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission--Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology. PMID:26501256

  19. [Prediction of antidepressant response to milnacipran and fluvoxamine using pharmacogenetical methods].

    PubMed

    Higuchi, Hisashi

    2010-04-01

    In a milnacipran study, ninety-six patients with major depressive disorder were treated with milnacipran, 50-100 mg/day, for 6 weeks. Severity of depression was assessed with the Montgomery and Asberg Depression Rating Scale. The purpose of this study was to determine whether norepinephrine transporter (NET) gene and serotonin transporter (5-HTT) gene polymorphisms are associated with the antidepressant response to milnacipran, a serotonin and norepinephrine reuptake inhibitor. Eighty patients completed the study. The presence of the T allele of the NET T-182C polymorphism was associated with a superior antidepressant response. In contrast, no influence of 5-HTTLPR (5-HTT linked polymorphic region) on the antidepressant response to milnacipran was detected. The results suggest that NET but not 5-HTT polymorphisms in part determine the antidepressant response to milnacipran. In a fluvoxamine study, sixty-six patients with major depressive disorder were treated with fluvoxamine, 100-200 mg/day, for 6 weeks. The authors investigated whether 5-HTTLPR was associated with the antidepressant response to fluvoxamine, a selective serotonin reuptake inhibitor. Fifty-seven patients completed the study. The short (s) allele frequency was significantly higher in the responsive individuals than in the nonresponsive ones. The results suggest that fluvoxamine is not less effective in depressive patients carrying the s allele than in those carrying the long (1) allele and it is not less effective in Japanese than in Caucasians. PMID:20491280

  20. Antidepressant Prescription and Suicide Rates: Effect of Age and Gender

    ERIC Educational Resources Information Center

    Kalmar, Sandor; Szanto, Katalin; Rihmer, Zoltan; Mazumdar, Sati; Harrison, Katrin; Mann, J. John

    2008-01-01

    To determine whether the effect of antidepressant exposure on suicide rate is modified by age and gender in Hungary, annual antidepressant prescription rates and suicide rates of about 10 million inhabitants between 1999-2005 were analyzed by age and gender groups. The suicide rate was inversely related to the increased use of antidepressants in…

  1. Vasopressin treatment for cyclic antidepressant overdose.

    PubMed

    Barry, James David; Durkovich, David W; Williams, Saralyn R

    2006-07-01

    Due to neurotransmitter reuptake inhibition, peripheral alpha receptor blocking effects, and sodium channel blockade, severe cyclic antidepressant poisoning may lead to intractable hypotension. We report a case of severe amitriptyline toxicity, with hypotension unresponsive to direct alpha receptor agonists after pH manipulation, but improved with intravenous vasopressin. Vasopressin use in the setting of cyclic antidepressant toxicity has not been previously reported. Vasopressin may be a beneficial agent in the treatment of recalcitrant hypotension associated with poisoning or overdose. The anecdotal nature of this report must be emphasized and the use of vasopressin requires further research to define efficacy, dose, and potential side effects. PMID:16798158

  2. A role for amines in the antidepressant effect of exercise: a review.

    PubMed

    Ransford, C P

    1982-01-01

    A review of the literature suggests that exercise may have antidepressant effects and, like other treatments for depression such as electroconvulsive therapy (ECT), antidepressant medication, and REM sleep deprivation, may enhance aminergic synaptic transmission in the central nervous system. In addition, the effects of exercise and other antidepressants on sleep are similar. Therefore, it is suggested that exercise is an antidepressant that enhances aminergic synaptic transmission in the central nervous system. Many more psychological and physiological studies must be performed in order to verify and quantify this relationship. Present statements that single out norepinephrine, dopamine, or serotonin as the crucial amine may be premature and oversimplified. Future physiological studies must take into consideration the advantages and disadvantages of human and animal subjects. Future psychological studies should be attentive to possible differences in psychological benefits between normal and depressed subjects and should not neglect the possible role of cognitive factors such as subjects' attitudes towards exercising or the feelings of accomplishment that may result from increased physical fitness. There is also a need to measure antidepressant effects in long-term exercise programs and in studies employing various forms of exercise. PMID:6280014

  3. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant

    PubMed Central

    Patel, Krisna; Allen, Sophie; Haque, Mariam N.; Angelescu, Ilinca; Baumeister, David; Tracy, Derek K.

    2016-01-01

    Bupropion has been used as an antidepressant for over 20 years, though its licence for such use varies and it is typically a third- or fourth-line agent. It has a unique pharmacology, inhibiting the reuptake of noradrenaline and dopamine, potentially providing pharmacological augmentation to more common antidepressants such as selective serotonergic reuptake inhibitors (SSRIs). This systematic review and meta-analysis identified 51 studies, dividing into four categories: bupropion as a sole antidepressant, bupropion coprescribed with another antidepressant, bupropion in ‘other’ populations (e.g. bipolar depression, elderly populations) and primary evaluation of side effects. Methodologically more robust trials support the superiority of bupropion over placebo, and most head-to-head antidepressant trials showed an equivalent effectiveness, though some of these are hindered by a lack of a placebo arm. Most work on the coprescribing of bupropion with another antidepressant supports an additional effect, though many are open-label trials. Several large multi-medication trials, most notably STAR*D, also support a therapeutic role for bupropion; in general, it demonstrated similar effectiveness to other medications, though this literature highlights the generally low response rates in refractory cohorts. Effectiveness has been shown in ‘other’ populations, though there is an overall dearth of research. Bupropion is generally well tolerated, it has very low rates of sexual dysfunction, and is more likely to cause weight loss than gain. Our findings support the use of bupropion as a sole or coprescribed antidepressant, particularly if weight gain or sexual dysfunction are, or are likely to be, significant problems. However there are notable gaps in the literature, including less information on treatment naïve and first presentation depression, particularly when one considers the ever-reducing rates of response in more refractory illness. There are some data to

  4. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant.

    PubMed

    Patel, Krisna; Allen, Sophie; Haque, Mariam N; Angelescu, Ilinca; Baumeister, David; Tracy, Derek K

    2016-04-01

    Bupropion has been used as an antidepressant for over 20 years, though its licence for such use varies and it is typically a third- or fourth-line agent. It has a unique pharmacology, inhibiting the reuptake of noradrenaline and dopamine, potentially providing pharmacological augmentation to more common antidepressants such as selective serotonergic reuptake inhibitors (SSRIs). This systematic review and meta-analysis identified 51 studies, dividing into four categories: bupropion as a sole antidepressant, bupropion coprescribed with another antidepressant, bupropion in 'other' populations (e.g. bipolar depression, elderly populations) and primary evaluation of side effects. Methodologically more robust trials support the superiority of bupropion over placebo, and most head-to-head antidepressant trials showed an equivalent effectiveness, though some of these are hindered by a lack of a placebo arm. Most work on the coprescribing of bupropion with another antidepressant supports an additional effect, though many are open-label trials. Several large multi-medication trials, most notably STAR*D, also support a therapeutic role for bupropion; in general, it demonstrated similar effectiveness to other medications, though this literature highlights the generally low response rates in refractory cohorts. Effectiveness has been shown in 'other' populations, though there is an overall dearth of research. Bupropion is generally well tolerated, it has very low rates of sexual dysfunction, and is more likely to cause weight loss than gain. Our findings support the use of bupropion as a sole or coprescribed antidepressant, particularly if weight gain or sexual dysfunction are, or are likely to be, significant problems. However there are notable gaps in the literature, including less information on treatment naïve and first presentation depression, particularly when one considers the ever-reducing rates of response in more refractory illness. There are some data to support

  5. Association between ABCB1 Polymorphisms and Antidepressant Treatment Response in Taiwanese Major Depressive Patients

    PubMed Central

    Chang, Hui Hua; Chou, Chen-Hsi; Yang, Yen Kuang; Lee, I Hui; Chen, Po See

    2015-01-01

    Objective The multidrug resistance 1 (ABCB1, MDR1) gene, encoding P-glycoprotein, is extensively distributed and expressed in various tissues, such as a blood-brain barrier transporter. P-glycoprotein plays an important role in controlling the passage of substances between the blood and brain. The current study aimed to investigate possible associations of functional ABCB1 polymorphisms (C3435T, G2677T and C1236T) with response to antidepressant treatment and serum cortisol levels in Taiwanese patients with major depressive disorder (MDD). Methods We recruited 112 MDD patients who were randomized to fluoxetine (n=58, mean dose: 21.4±4.5 mg/day) or venlafaxine (n=54, 80.2±34.7 mg/day) treatment for 6 weeks. The 21-item Hamilton Depression Rating Scale (HDRS) was administered initially and biweekly after treatment, and cortisol levels were assessed initially and after 6-week antidepressant treatment. Results The initial HDRS scores and the HDRS scores after six weeks of antidepressant treatment were not significantly different among the different genotypes in each polymorphism of ABCB1. The percentage changes of HDRS scores over time were significantly different in the polymorphisms of ABCB1 G2677T (p=0.002). MDD patients with the G/G genotype of ABCB1 G2677T had a worse antidepressant treatment response. However, the polymorphisms of ABCB1 genotypes were not significantly associated with cortisol levels before and after antidepressant treatment in MDD patients. Conclusion The results suggested that the variants of ABCB1 may influence the short-term antidepressant response in MDD patients. Further details of the underlying mechanisms of ABCB1 in antidepressant treatment remain to be clarified. PMID:26598582

  6. Involvement of the central monoaminergic system in the antidepressant-like effect of catalpol in mice.

    PubMed

    Wang, Junming; Cui, Ying; Feng, Weisheng; Zhang, Yueyue; Wang, Guifang; Wang, Xingxing; Zhou, Gai

    2014-10-01

    Catalpol is a natural iridoid glycoside with diverse bioactivities that is found in abundance in Rehmannia glutinosa Libosch. (Scrophulariaceae). The present study assessed whether catalpol treatment (5, 10, or 20 mg/kg for 14 days by intragastric administration (i.g.)) has an antidepressant-like effect on mice performing the forced swim test (FST), tail suspension test (TST), open field test (OFT), and tests for reversal of reserpine-induced ptosis, akinesia, and hypothermia. This study also examined the potential role that catalpol plays in the cerebral monoaminergic system. Results indicated that catalpol administration produced an antidepressant-like effect in mice, as indicated by the reduced duration of immobility in the FST and TST, but it had no effect on locomotor activity in the OFT. Catalpol treatment significantly counteracted the decrease in rectal temperature, akinesia, and eyelid ptosis induced by reserpine. Moreover, catalpol increased levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the brains of mice, but it did not affect levels of norepinephrine (NE) or dopamine (DA). These antidepressant-like effects of catalpol are essentially similar to the effects of the clinical antidepressant fluoxetine hydrochloride (FH). This is the first study to indicate that catalpol has an antidepressant-like effect and that its action may be mediated by the central serotonergic system, and not by noradrenergic or dopaminergic systems. PMID:25382440

  7. Is increased antidepressant exposure a contributory factor to the obesity pandemic?

    PubMed

    Lee, S H; Paz-Filho, G; Mastronardi, C; Licinio, J; Wong, M-L

    2016-01-01

    Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic-pituitary-adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination of

  8. Is increased antidepressant exposure a contributory factor to the obesity pandemic?

    PubMed Central

    Lee, S H; Paz-Filho, G; Mastronardi, C; Licinio, J; Wong, M-L

    2016-01-01

    Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic–pituitary–adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination

  9. Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.

    PubMed

    de Mello Schier, Alexandre R; de Oliveira Ribeiro, Natalia P; Coutinho, Danielle S; Machado, Sergio; Arias-Carrión, Oscar; Crippa, Jose A; Zuardi, Antonio W; Nardi, Antonio E; Silva, Adriana C

    2014-01-01

    Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor. PMID:24923339

  10. Evaluation of Antidepressant-like Effect of Citrus Maxima Leaves in Animal Models of Depression

    PubMed Central

    Potdar, Vikram H; Kibile, Swati J

    2011-01-01

    Objective(s) This study planned to assess antidepressant like activity of aqueous extract from leaves of Citrus maxima Merr. (Rutaceae). Materials and Methods Boiling was used for aqueous extraction. Acute toxicity study was performed in mice. Antidepressant activity was studied using locomotor activity test, modified forced swimming test (FST) and tail suspension test (TST). Three doses 100, 200 and 300 mg/kg of aqueous extract of leaves were selected for testing. Fluoxetine (20 mg/kg, i.p.) and imipramine (30 mg/kg, i.p.) were used as the standard drugs. Results Aqueous extract of Citrus maxima leaves significantly reduced immobility time in both TST and FST. In locomotor activity testing it showed psychostimulant effect. Extract increased the climbing behavior in FST, which is similar to effect observed with imipramine. Conclusion The results of this study suggest that antidepressant like effect of Citrus maxima seems to be mediated by an increase in norepinephrine level in synapses. PMID:23492865

  11. Inflammatory biomarkers as differential predictors of antidepressant response.

    PubMed

    Hashimoto, Kenji

    2015-01-01

    Although antidepressants are generally effective in the treatment of major depressive disorder (MDD), it can still take weeks before patients feel the full antidepressant effects. Despite the efficacy of standard treatments, approximately two-thirds of patients with MDD fail to respond to pharmacotherapy. Therefore, the identification of blood biomarkers that can predict the treatment response to antidepressants would be highly useful in order to improve this situation. This article discusses inflammatory molecules as predictive biomarkers for antidepressant responses to several classes of antidepressants, including the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. PMID:25856677

  12. Antidepressant Effects of AMPA and Ketamine Combination: Role of Hippocampal BDNF, Synapsin, and mTOR

    PubMed Central

    Akinfiresoye, Luli; Tizabi, Yousef

    2013-01-01

    Rationale A number of preclinical and clinical studies suggest ketamine, a glutamate NMDA (N-methyl-D-aspartate) receptor antagonist, has a rapid and lasting antidepressant effect when administered either acutely or chronically. It has been postulated that this effect is due to stimulation of AMPA (alpha-amino-3-hydroxy-5-methyl–4-isoxazolepropionic acid) receptors. Objective In this study, we tested whether AMPA alone has an antidepressant effect and if the combination of AMPA and ketamine provides added benefit in Wistar-Kyoto (WKY) rats, a putative animal model of depression. Results Chronic AMPA treatment resulted in a dose dependent antidepressant effect in both the forced swim test (FST) and sucrose preference test. Moreover, chronic administration (10–11d) of combinations of AMPA and ketamine, at doses that were ineffective on their own, resulted in a significant antidepressant effect. The behavioral effects were associated with increases in hippocampal brain derived neurotrophic factor (BDNF), synapsin, and mammalian target of rapamycin (mTOR). Conclusion These findings are the first to provide evidence for an antidepressant effect of AMPA, and suggest the usefulness of AMPA-ketamine combination in treatment of depression. Furthermore, these effects appear to be associated with increases in markers of hippocampal neurogenesis and synaptogenesis, suggesting a mechanism of their action. PMID:23732839

  13. [Use of antidepressants in the treatment of negative symptoms of schizophrenia].

    PubMed

    Palomba, A; Lodovighi, M-A; Belzeaux, R; Adida, M; Azorin, J-M

    2015-12-01

    Negative symptoms account for a clinical dimension of schizophrenia. They are partly the cause of functional disability of this disease. Clinical experience shows that antipsychotics have little or no effect on these symptoms. The aim of this review is to gather existing data on the treatment of negative symptoms with antidepressants. The combination of antipsychotics with antidepressants is a therapeutic strategy commonly used for the treatment of these symptoms. The pro-dopaminergic effects of antidepressants explain their effectiveness on negative symptoms. There are many comparative, randomized, controlled studies evaluating the efficacy of antidepressant associated with antipsychotic for the treatment of negative symptoms. Furthermore three meta-analyses have been conducted. The overall results suggest that the use of antidepressants may contribute to clinical improvement of negative symptoms in schizophrenia. The limitations of these studies are the small number of patients included and the definition and assessment of negative symptoms. The existing scales are not sufficiently discriminating. Further research using new measurement tools should help refine these results. PMID:26776391

  14. Physiological Bases of Bulimia, and Antidepressant Treatment.

    ERIC Educational Resources Information Center

    Getzfeld, Andrew R.

    This paper reviews the literature on the physiological causes of bulimia and investigates the rationale behind the usage of antidepressant medication in the treatment of bulimia nervosa. No definite conclusions can be stated regarding the physiology of bulimia, but a number of hypotheses are suggested. It appears that the hypothalamus is involved…

  15. Synthesis of the Commercial Antidepressant Moclobemide

    ERIC Educational Resources Information Center

    More, Jesse D.

    2008-01-01

    An experiment for the undergraduate organic chemistry laboratory is described in which students synthesize the commercial antidepressant drug moclobemide, marketed under the trade name Manerix. This one-step synthesis starts from commercially available material and produces moclobemide in high yield. The product is initially isolated as its…

  16. Anti-Depressants, Suicide, and Drug Regulation

    ERIC Educational Resources Information Center

    Ludwig, Jens; Marcotte, Dave E.

    2005-01-01

    Policymakers are increasingly concerned that a relatively new class of anti-depressant drugs, selective serotonin re-uptake inhibitors (SSRI), may increase the risk of suicide for at least some patients, particularly children. Prior randomized trials are not informative on this question because of small sample sizes and other limitations. Using…

  17. [Therapy of dementia with antipsychotics and antidepressives].

    PubMed

    Frölich, L; Hausner, L

    2015-04-01

    In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia. PMID:25787724

  18. Characterizing declines in pediatric antidepressant use after new risk disclosures

    PubMed Central

    Frank, Richard G.; Martin, Andres; Barry, Colleen L.

    2010-01-01

    Steep declines in pediatric antidepressant use were documented following the 2004 release of new safety information associating antidepressants with a risk of suicidality. We examine whether declines in pediatric antidepressant use were steeper among individuals with certain clinical or family characteristics. We find that declines in antidepressant use were associated with new (as compared to ongoing) treatment episodes. Also, although rates of antidepressant use were higher among children of college educated parents prior to risk disclosures, these children were more likely to forgo antidepressant medication than children of less educated parents after risk disclosures. We find that both children with and without psychiatric impairment experienced declines in antidepressant medication use following the risk warnings, although the decline occurred more quickly in the latter group. Our findings highlight the need for additional data to assess the effects of risk disclosures on treatment patterns and health outcomes. PMID:20675349

  19. Therapeutic equivalence of antipsychotics and antidepressants - A systematic review.

    PubMed

    Cessak, Grzegorz; Rokita, Konrad; Dąbrowska, Marta; Sejbuk-Rozbicka, Katarzyna; Zaremba, Anna; Mirowska-Guzel, Dagmara; Bałkowiec-Iskra, Ewa

    2016-04-01

    The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order for any generic drug to receive an approval of regulatory authorities, its bioequivalence with the corresponding reference product must be demonstrated. Moreover, generic drugs must meet the same quality standards as reference drugs. However, many psychiatrists express concerns about use of generic drugs. We carried out a systematic analysis of the relevant literature indexed in PubMed and Cochrane databases. The MeSH term "generic" was combined with terms describing antipsychotic and antidepressive drugs, including their pharmaceutical names and relevant mental disorders. All 26 articles including either clinical studies or case reports have been qualified for a detailed analysis. No cases describing switches between two generics were found. Therapeutic equivalence studies evaluating antipsychotics included clozapine, olanzapine, and risperidone. The clinical status was judged to have worsened in 15.7% patients treated with clozapine. The number of relapses before and after the switch was not significantly different in patients treated with olanzapine. Two case reports showed clinical state deterioration after switch to generic risperidone. The clinical outcome after conversion to a generic antidepressant was evaluated only in one retrospective study. That study analyzed the outcomes of treatment with citalopram and revealed mental state deterioration in 11.6% of patients. Only single reports describe cases of impaired efficacy or adverse events after the switch to a generic antidepressant, including fluoxetine, mirtazapine, and venlafaxine. No cases of suicidal attempt after the switch were reported. Although the overall number of described cases is rather modest, health professionals should be aware of possible changes in the therapeutic effectiveness after changing to a generic medicine. PMID

  20. The multiple outcomes bias in antidepressants research.

    PubMed

    Procopio, Marco

    2005-01-01

    Despite the widespread use of antidepressant medication, there are no signs that the burden of depression and suicide is decreasing in the industrialised world. This is generating mounting scepticism on the effectiveness of this class of drugs as an approach for the treatment of mood disorders. These doubts are also fuelled by the increasing awareness that the literature on antidepressants is fundamentally flawed and under the control of the pharmaceutical companies. This article describes systematically for the first time what is probably the most insidious and misleading of the biases that affect this area of research: the "multiple outcomes bias". Most trials on the effectiveness of antidepressants, instead of first establishing a hypothesis and then trying to demonstrate it, following the scientific method, start instead "data mining", without a clear hypothesis, and then select for publication, amongst a multitude of outcomes, only the ones that favour the antidepressant drug, ignoring the others. This method has obviously no scientific validity and is very misleading, allowing the manipulation of the data without any overt fraudulent action. There is the need to generate new research, independently funded and with clear hypotheses established "a priori ". What is at stake is not only the appraisal of the balance between benefits and potential damage to the patients when using this class of medications, after the realisation that they are not as harmless as believed. It is also to establish whether the research on antidepressant medication has gone on a "wild goose chase" over the last half century, concentrating almost exclusively on molecules that modify the monoaminergic transmission at synaptic level and virtually ignoring any other avenue. PMID:15922120

  1. Does melatonin treatment change emotional processing? Implications for understanding the antidepressant mechanism of agomelatine.

    PubMed

    Pringle, Abbie; Bogdanovskaya, Maria; Waskett, Poppy; Zacharia, Sophie; Cowen, Philip J; Harmer, Catherine J

    2015-10-01

    The antidepressant, agomelatine, has a novel pharmacological profile, with agonist properties at M1 and M2 receptors and antagonist properties at 5HT2C receptors. Whether the antidepressant effects of this treatment are mediated by the drug's effects at the M1 and M2 receptors or the 5HT2C receptor or a synergy between these actions remains unclear. In the present study, a healthy volunteer model of emotional processing, which discriminates between effective and non-effective antidepressant compounds, was used to assess the contribution of melatonin agonism to the efficacy of agomelatine. Fifty-eight healthy volunteers were randomised to receive 7 days of once daily treatment with either 1 mg melatonin, 3 mg melatonin or placebo. Seven days treatment with 3 mg melatonin resulted in earlier bedtimes consistent with a phase advance in circadian rhythm. Some marginal effects of melatonin were observed on emotional processing; however, these were neither consistent with nor comparable to those seen following conventional antidepressant treatment or with agomelatine itself. These data suggest that the antidepressant action of agomelatine cannot be accounted for solely by its action at the M1 and M2 receptors. PMID:26174133

  2. Effectiveness of antidepressants and predictors of treatment response for depressed HIV patients in Uganda.

    PubMed

    Ngo, Victoria K; Wagner, Glenn J; Nakasujja, Noeline; Dickens, Akena; Aunon, Frances; Musisi, Seggane

    2015-12-01

    Antidepressant medication is well established for the treatment of depression but little is known about its effectiveness for HIV populations in sub-Saharan Africa. This study examined the effectiveness of antidepressant treatment and predictors of treatment response among depressed HIV patients in Uganda. Data were obtained from two open-label trials in which 184 HIV patients were diagnosed with depression and started on antidepressants. Data at treatment baseline and month 6 were compared to assess treatment response, and baseline predictors of response were assessed. A total of 154 completed month 6, of whom 122 (79%) had responded to treatment and were no longer depressed (Patient Health Questionnaire-9, score < 5). Bivariate analysis found that education, CD4 count, general health functioning, physical health, pain, quality of life and social support variables were associated with antidepressant treatment response; however, only secondary education and social support independently predicted treatment response in logistic multiple regression analysis. Baseline depression severity was not associated with treatment response. In conclusion, antidepressants are effective in treating both moderate and more severe depression among persons living with HIV in Uganda, and education [OR (95% CI) = 4.33 (1.33-14.11)] and social support [OR (95% CI) = 1.54 (1.03-2.30)] were most predictive of treatment response. PMID:25525053

  3. [Antidepressant-resistant depression and bipolar spectrum - diagnostic and therapeutic considerations].

    PubMed

    Rihmer, Zoltán; Gonda, Xénia; Rihmer, Annamária; Döme, Péter

    2016-01-01

    According to the results of epidemiological studies mood disorders with unipolar (major and minor depressive disorder; dysthymia) or bipolar features are among the most prevalent psychiatric disorders. These disorders with their frequent comorbidities (alcohol and/or drug use disorders, smoking, suicide, cardiovascular disorders) pose great public health challenge and cause substantial individual and familar burdens as well. Since SSRIs and other new antidepressant agents entered the market the possibilities to treat depression improved substantially but 25-35 percent of major depressives do not respond even to the second antidepressant trial but the rate of patients who are resistant after the third and fourth adequate antidepressant trial are around only 15-25 and 10 percent, respectively. Pharmacotherapy-resistant depression is a multicausal phenomenon. Along with its well-known risk-factors investigations of the past decade have revealed that unrecognised or hidden (subsyndromal or subthreshold) bipolarity is one of the most frequent causes of treatment resistance. In the case of bipolar depression (either as a part of syndromal bipolar I or II disorder or a subsyndromal manifestation) antidepressant monotherapy should be avoided and, instead of it, the administration of a mood stabilizer (primarily lithium and lamotrigine) or some atypical antipsychotics (preferably quetiapine) are recommended. If antidepressant is inevitably necessary in bipolar depression, we should use it always in combination with mood stabilizers or atypical antipsychotics. PMID:27244871

  4. Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores

    PubMed Central

    Werner, Anna M.; Cuboni, Serena; Rudolf, Georg C.; Höfner, Georg; Wanner, Klaus T.; Sieber, Stephan A.; Schmidt, Ulrike; Holsboer, Florian; Rein, Theo; Hausch, Felix

    2016-01-01

    The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes. PMID:26863431

  5. [An exploration in the action targets for antidepressant bioactive components of Xiaoyaosan based on network pharmacology].

    PubMed

    Gao, Yao; Gao, Li; Gao, Xiao-xia; Zhou, Yu-zhi; Qin, Xue-mei; Tian, Jun-sheng

    2015-12-01

    The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan. PMID:27169281

  6. Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores.

    PubMed

    Kirmeier, Thomas; Gopalakrishnan, Ranganath; Gormanns, Vanessa; Werner, Anna M; Cuboni, Serena; Rudolf, Georg C; Höfner, Georg; Wanner, Klaus T; Sieber, Stephan A; Schmidt, Ulrike; Holsboer, Florian; Rein, Theo; Hausch, Felix

    2016-01-01

    The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes. PMID:26863431

  7. The mesolimbic dopamine system as a target for rapid antidepressant action.

    PubMed

    Willner, P

    1997-07-01

    Chronic treatment with antidepressant drugs produces a variety of changes in dopaminergic neurotransmission, most notably a sensitization of behavioural responses to agonists acting at dopamine D2/D3 receptors within the nucleus accumbens. Evidence from animal models of depression (the forced swim test and the chronic mild stress procedure) indicates that these effects are crucial for the therapeutic effect of antidepressants in these models. Antidepressant-like effects in animal models are also seen with drugs that act directly on the dopaminergic system. Because of its prolonged time-course, the chronic mild stress procedure can be used to examine onset latencies. Some dopamine-active drugs (e.g. the catechol-O-methyltransferase inhibitor tolcapone; D2/D3 agonists administered intermittently) are active in this procedure but have a time-course comparable to that of conventional antidepressants. Other dopamine-active drugs may have a more rapid onset; the evidence to date suggests this possibility for the D2/D3 agonist pramipexole and the preferential presynaptic antagonist amisulpride. In clinical studies, rapid-onset latencies have been claimed for the D2/D3 agonist roxindole, the preferential presynaptic antagonist sulpiride and the relatively selective dopamine-uptake inhibitor amineptine. The mechanisms that might give rise to a rapid onset of dopamine-mediated antidepressant effects are discussed. PMID:9347387

  8. Discontinuation of Antidepressants During Attempts to Conceive

    PubMed Central

    Psaros, Christina; Freeman, Marlene; Safren, Steven A.; Barsky, Maria; Cohen, Lee S.

    2016-01-01

    Background Many women discontinue antidepressants (ADs) when trying to conceive, although risk of depressive relapse is high. We examined the feasibility and potential clinical effect of cognitive behavioral therapy for the prevention of recurrence (CBT-PR) for women with a history of recurrent major depressive disorder (MDD) who planned to discontinue maintenance AD treatment for pregnancy. Methods This was an open preliminary study of CBT-PR in women (N = 12) planning or early in pregnancy with remitted MDD on maintenance ADs with a plan to discontinue ADs for pregnancy. Participants received 12 sessions of CBT-PR during the acute phase and optional monthly booster sessions during follow-up. Participants were assessed monthly during the acute phase and then twice additionally during follow-up by an independent rater using mood scales (depression module of the Mini-International Neuropsychiatric Interview and Montgomery-Åsberg Depression Rating Scale); pregnancy status was also assessed. Results Over the 24 weeks of the trial, 75% (n = 9) of participants did not restart ADs and did not relapse to depression. Of the 3 who reintroduced AD, 2 experienced a depressive relapse, whereas one did not meet full criteria for MDD. Adherence to the intervention was very good with all participants completing all therapy sessions and assessments. Conclusions Cognitive behavioral therapy for the prevention of recurrence seems feasible and may provide protection for women with recurrent depression on ADs who discontinue their medication while trying to conceive. The extent to which euthymia is sustainable with CBT-PR requires further study; the results of which may broaden treatment choices for women in anticipation of and during pregnancy. PMID:24911438

  9. Obesity and Its Potential Effects on Antidepressant Treatment Outcomes in Patients with Depressive Disorders: A Literature Review

    PubMed Central

    Woo, Young Sup; Seo, Hye-Jin; McIntyre, Roger S.; Bahk, Won-Myong

    2016-01-01

    Accumulating evidence regarding clinical, neurobiological, genetic, and environmental factors suggests a bidirectional link between obesity and depressive disorders. Although a few studies have investigated the link between obesity/excess body weight and the response to antidepressants in depressive disorders, the effect of weight on treatment response remains poorly understood. In this review, we summarized recent data regarding the relationship between the response to antidepressants and obesity/excess body weight in clinical studies of patients with depressive disorders. Although several studies indicated an association between obesity/excess body weight and poor antidepressant responses, it is difficult to draw definitive conclusions due to the variability of subject composition and methodological differences among studies. Especially, differences in sex, age and menopausal status, depressive symptom subtypes, and antidepressants administered may have caused inconsistencies in the results among studies. The relationship between obesity/excess body weight and antidepressant responses should be investigated further in high-powered studies addressing the differential effects on subject characteristics and treatment. Moreover, future research should focus on the roles of mediating factors, such as inflammatory markers and neurocognitive performance, which may alter the antidepressant treatment outcome in patients with comorbid obesity and depressive disorder. PMID:26771598

  10. Regulation of proteolytic cleavage of brain-derived neurotrophic factor precursor by antidepressants in human neuroblastoma cells

    PubMed Central

    Lin, Pao-Yen

    2015-01-01

    Evidence has supported the role of brain-derived neurotrophic factor (BDNF) in antidepressant effect. The precursor of BDNF (proBDNF) often exerts opposing biological effects on mature BDNF (mBDNF). Hence, the balance between proBDNF and mBDNF might be critical in total neurotrophic effects, leading to susceptibility to or recovery from depression. In the current study, we measured the protein expression levels of proBDNF, and its proteolytic products, truncated BDNF, and mBDNF, in human SH-SY5Y cells treated with different antidepressants. We found that the treatment significantly increased the production of mBDNF, but decreased the production of truncated BDNF and proBDNF. These results support that antidepressants can promote proBDNF cleavage. Further studies are needed to clarify whether proBDNF cleavage plays a role in antidepressant mechanisms. PMID:26491331

  11. Antidepressant-coincident mania in children and adolescents treated with selective serotonin reuptake inhibitors

    PubMed Central

    Joseph, Megan F; Youngstrom, Eric A; Soares, Jair C

    2009-01-01

    Several factors have amplified concern about the possibility that antidepressant medication may contribute to induction of pediatric mania. These include the high rate of antidepressant medication prescription, the recent surge in the rate of diagnosis of pediatric bipolar disorder in the USA, and a growing number of case reports and clinical studies showing coincidence of manic symptoms with antidepressant pharmacotherapy in both youths and adults. However, the question of how medications and manic symptoms might be related is complicated, and decisive research studies with rigorous designs for evaluating the issues have not been published. The situation makes it difficult for practitioners to make good, evidence-based decisions. The scientific literature is ambiguous, and the stakes are high. We review the extant literature, offer seven different conceptual models of how medication and mania might be related, and comment on the evidence and clinical implications of each. PMID:19884978

  12. [Between depression and fibroniyalgia: the fate of the antidepressant].

    PubMed

    Drobizhev, M Yu; Fedotova, A V; Kikta, S V; Antokhin, E Yu

    2016-01-01

    The authors present the information about one of the least studied antidepressants- milnacipran. Recommendations of its clinical use have been long based on incorrect conceptions of its pharmacological properties. Currently, milnacipran is considered as ancirepinephrine and serotonin (to a lesser degree) reuptake inhibitor and NMDA receptor blocker. Milnacipran can be successfully used in apatic, asthenic, adynamic and anhedonic depressions as well as in fibromyalgia in patients with marked fatigability and pain. However the recommendations for the latter are not registered in Russia (maybe due to the differences in the diagnosis of fibromyalgia which is traditionally more often diagnosed as neurasthenia). PMID:27386594

  13. Antidepressant Effects of Resveratrol in an Animal Model of Depression

    PubMed Central

    Akinfiresoye, Laura L. Hurley, Luli; Kalejaiye, Olubukola; Tizabi, Yousef

    2014-01-01

    Resveratrol (3,4’,5-trihydroxy-trans-stilbene) is a natural non-flavonoid polyphenol antioxidant extracted from red grapes in the processing of wine. Initially it was studied for its potential as anticancer drug, and later was found to reduce cardiovascular disease. More recently resveratrol was shown to alleviate depressive-like symptoms induced by stress or other means in mice and rats. The major purpose of this study was to investigate whether resveratrol would manifest an antidepressant effect in Wistar-Kyoto (WKY) rats, a putative and non-induced animal model of depression, and whether this effect might be associated with an increase in hippocampal and frontal cortical brain-derived neurotrophic factor (BDNF), a protein implicated in chronic effects of many antidepressants. Adult male WKY rats were injected with two doses of resveratrol (10 and 40 mg/kg, i.p.) and their behavior in the open field locomotor activity (LMA), forced swim test (FST: a measure of helplessness), and sucrose preference test (SPT: a measure of anhedonia) was evaluated after a single acute injection or following 7 days of daily treatment. Both acute and chronic administration of resveratrol resulted in a dose-dependent decrease in FST. However, only chronic resveratrol resulted in dose-dependent increase in sucrose consumption. LMA was not affected by any treatment. Parallel to the observed behavioral effects the level of hippocampal, but not frontal cortical, BDNF was also dose-dependently elevated after chronic resveratrol administration. These findings indicate an antidepressant-like effect of resveratrol in an animal model of depression possibly via activation of hippocampal BDNF, and suggest therapeutic potential of resveratrol in at least a subpopulation of depressed patients. PMID:24717328

  14. The impact of direct-to-consumer television and magazine advertising on antidepressant use.

    PubMed

    Avery, Rosemary J; Eisenberg, Matthew D; Simon, Kosali I

    2012-09-01

    We examine whether exposure to direct-to-consumer advertising (DTCA) for antidepressant drugs affects individual use of these medications among those suffering from depression. Prior studies have almost exclusively relied on making connections between national or market-level advertising volume/expenditures and national or individual-level usage of medications. This is the first study to: estimate the impact of individual-level exposure to DTCA on individual-level use of antidepressants; estimate the impact of individual-level exposure to television DTCA on individual-level use in any drug class; consider the relative and interactive impact of DTCA in two different media in any drug class; and, consider the heterogeneity of impact among different populations in an econometric framework in the antidepressant market. There are also important limitations to note. Unlike prior market level studies that use monthly data, we are limited to aggregated annual data. Our measures of potential advertising exposure are constructed assuming that media consumption patterns are stable during the year. We are also not able to study the impact of advertising on use of antidepressants for conditions other than depression, such as anxiety disorders. We find that: DTCA impacts antidepressant use in a statistically and economically significant manner; that these effects are present in both television and magazine advertising exposure but do not appear to have interactive effects; are stronger for women than for men in the magazine medium, but are about equally strong for men and women in the TV medium; and, are somewhat stronger for groups suffering from more severe forms of depression. The overall size of the effect is a 6-10 percentage point increase in antidepressant use from being exposed to television advertising; the corresponding magazine effects are between 3 and 4 percentage points. PMID:22835472

  15. Rifaximin has a Marginal Impact on Microbial Translocation, T-cell Activation and Inflammation in HIV-Positive Immune Non-responders to Antiretroviral Therapy – ACTG A5286

    PubMed Central

    Tenorio, Allan R.; Chan, Ellen S.; Bosch, Ronald J.; Macatangay, Bernard J. C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam; Presti, Rachel; Deeks, Steven; Ebiasah, Ruth; Myers, Laurie; Borowski, LuAnn; Plants, Jill; Palm, David A.; Weibel, Derek; Putnam, Beverly; Lindsey, Elizabeth; Player, Amy; Albrecht, Mary; Kershaw, Andrea; Sax, Paul; Keenan, Cheryl; Walton, Patricia; Baum, Jane; Stroberg, Todd; Hughes, Valery; Coster, Laura; Kumar, Princy N.; Yin, Michael T.; Noel-Connor, Jolene; Tebas, Pablo; Thomas, Aleshia; Davis, Charles E.; Redfield, Robert R.; Sbrolla, Amy; Flynn, Teri; Davis, Traci; Whitely, Kim; Singh, Baljinder; Swaminathan, Shobha; McGregor, Donna; Palella, Frank; Aberg, Judith; Cavanagh, Karen; Santana Bagur, Jorge L.; Flores, Olga Méndez; Fritsche, Janice; Sha, Beverly; Slamowitz, Debbie; Valle, Sandra; Tashima, Karen; Patterson, Helen; Harber, Heather; Para, Michael; Eaton, Molly; Maddox, Dale; Currier, Judith; Cajahuaringa, Vanessa; Luetkemeyer, Annie; Dwyer, Jay; Fichtenbaum, Carl J.; Saemann, Michelle; Ray, Graham; Campbell, Thomas; Fischl, Margaret A.; Bolivar, Hector; Oakes, Jonathan; Chicurel-Bayard, Miriam; Tripoli, Christine; Weinman, D. Renee; Adams, Mary; Hurley, Christine; Dunaway, Shelia; Storey, Sheryl; Klebert, Michael; Royal, Michael

    2015-01-01

    Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). Methods. HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4+ T-cell counts <350 cells/mm3 were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Results. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8+T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. Conclusions. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8+T-cell activation. Trial registration number. NCT01466595. PMID:25214516

  16. Antidepressant efficacy of high and low frequency transcranial magnetic stimulation in the FSL/FRL genetic rat model of depression.

    PubMed

    Hesselberg, Marie Louise; Wegener, Gregers; Buchholtz, Poul Erik

    2016-11-01

    Repetitive Magnetic Stimulation (rTMS) has appeared to be a potential non-invasive antidepressant method, which implies non-convulsive focal stimulation of the brain through a time varying magnetic field. The antidepressant potential of rTMS has been supported by animal studies showing a number of interesting similarities between magnetic stimulation and electroconvulsive stimulation (ECS). Despite these positive results, this method still contains many unknown issues. Importantly, there are fundamental uncertainties concerning the optimal combination of stimulus parameters (frequency, intensity, duration, and number of pulses) to obtain an antidepressant effect. Therefore, the present study aimed to qualify the choice of rTMS stimulus frequency in a well-validated genetic animal model of depression, the FSL/FRL rats. We compared the antidepressant effect of low frequency, high frequency rTMS and ECS to sham treatment in FRL and FSL rats using 6 parallel groups. We used the Forced Swim Test and the Open Field Test to screen the depression-like state in rats. We found that both the high frequency and the low frequency rTMS resulted in a significant antidepressant effect. However, this effect was inferior to the effect of ECS. The low frequency and high frequency groups, which received the same total impulse load and stimulus intensity, did not differ with respect to antidepressant efficacy in this study. In conclusion, this study provides robust evidence that both rTMS interventions are efficacious, although not as efficient as ECS. PMID:27473004

  17. Antidepressant-like effect of centrally acting non-narcotic antitussive caramiphen in a forced swimming test.

    PubMed

    Kawaura, Kazuaki; Miki, Risa; Shima, Eriko; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2010-09-13

    Recently, we reported that a centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test in rats. Because pharmacological properties of tipepidine apparently differ from those of typical antidepressants developed to date, we speculated that caramiphen, another centrally acting antitussive, has an antidepressant-like effect. That effect of caramiphen was studied in rats using the forced swimming test. Caramiphen at 20 and 40mg/kg i.p. significantly reduced immobility. At 40mg/kg i.p., it increased climbing behavior. Even at 40mg/kg, this drug had no effect on locomotor activity. Results suggest that a centrally acting antitussive possessing inhibition of GIRK channels has an antidepressant-like effect. PMID:20621160

  18. Ketamine as a promising prototype for a new generation of rapid-acting antidepressants

    PubMed Central

    Abdallah, Chadi G.; Averill, Lynnette A.; Krystal, John H.

    2015-01-01

    The discovery of ketamine’s rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with transient mild to moderate adverse effects during infusion. However, the optimal dosing and route of administration and the safety of chronic treatment is not fully known. This review summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action that may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets. Moreover, we offer suggestions for future research that can continue to advance the field forward and ultimately improve the psychopharmacologic interventions available for those individuals struggling with depressive and trauma-related disorders. PMID:25727103

  19. Extrapyramidal symptoms and antidepressant drugs: neuropharmacological aspects of a frequent interaction in the elderly.

    PubMed

    Govoni, S; Racchi, M; Masoero, E; Zamboni, M; Ferini-Strambi, L

    2001-03-01

    Depression is the most prevalent functional psychiatric disorder in late life. The problem of motor disorders associated with antidepressant use is relevant in the elderly. Elderly people are physically more frail and more likely to be suffering from physical illness, and any drug given may exacerbate pre-existing diseases, or interact with other drug treatments being administered for physical conditions. Antidepressants have been reported to induce extrapyramidal symptoms, including parkinsonism. These observations prompted us to review the neurobiological mechanism that may be involved in this complex interplay including neurotransmitters and neuronal circuits involved in movement and emotion control and their changes related to aging and disease. The study of the correlations between motor and mood disorders and their putative biochemical bases, as presented in this review, provide a rationale either to understand or to foresee motor side effects for psychotropic drugs, in particular antidepressants. PMID:11317214

  20. Effects of Buprenorphine on Behavioral Tests for Antidepressant and Anxiolytic Drugs in Mice

    PubMed Central

    Falcon, Edgardo; Maier, Kaitlyn; Robinson, Shivon A.; Hill-Smith, Tiffany E.; Lucki, Irwin

    2014-01-01

    Rationale Buprenorphine (BPN) has been shown to rapidly improve mood in treatment-resistant depressed patients in small clinical studies. However, BPN’s effects in preclinical tests for mood and antidepressant efficacy are largely unexplored. Objective The current study examined the effects of BPN in the forced swim test (FST) and novelty-induced hypophagia (NIH) test as measures of antidepressant and anxiolytic-like effects in C57BL/6J mice. Microdialysis was used to measure whether BPN engaged KORs in the nucleus accumbens shell (NAcSh) at a behaviorally active dose (0.25 mg/kg). Methods BPN was tested in the FST at both 30 min and 24 h post administration. Also measured in the FST at 24 h post administration were the KOR antagonist norbinaltorphimine (nor-BNI), the MOR agonist morphine and the reference antidepressant desipramine. The anxiolytic effects of BPN were examined in the NIH test 24 h after treatment. The effects of acute injection of BPN and the KOR agonist U50,488 were measured on extracellular DA levels in the NAcSh. Results BPN produced significant reductions in FST immobility without changing locomotor activity and reduced approach latencies in the novel environment of the NIH test when tested 24 h after treatment. Repeated daily BPN injections for 6 d did not produce tolerance to these behavioral effects. nor-BNI produced a similar antidepressant-like response in the FST 24 h postinjection but morphine and desipramine were ineffective. BPN (0.25 mg/kg) did not alter DA levels when given alone but prevented the KOR agonist U50,488 from reducing DA levels. Conclusions Acute and subchronic treatment with BPN produced antidepressant and anxiolytic-like responses in mice at doses that engage KORs. These studies support the clinical evidence that BPN may be a novel rapid-acting antidepressant medication and provides rodent models for investigating associated neurochemical mechanisms. PMID:25178815

  1. [Antidepressants, stressors and the serotonin 1A receptor].

    PubMed

    Kirilly, Eszter; Gonda, Xénia; Bagdy, György

    2015-06-01

    5-HT(1A) receptor is a receptor of surprises. Buspirone, an anxiolytic drug with a then yet unidentified mechanism of action had been marketed for years when it was discovered that it is a 5-HT(1A) partial agonist. Several more years had to pass before it was accepted that this receptor plays the key role in the action mechanism of buspirone. This was followed by further surprises. It was discovered that in spite of its anxiolytic effect buspirone activates the hypothalamic-pituitary-adrenal (HPA) stress axis, furthermore, it increases peripheral noradrenaline and adrenaline concentration via a central mechanism. Thus activation of this receptor leads to ACTH/corticosterone and catecholamine release and also increases beta-endorphine, oxytocin and prolactin secretion while decreasing body temperature, increasing food uptake, eliciting characteristic behavioural responses in rodents and also playing a role in the development of certain types of epilepsy. Human genetic studies revealed the role of 5-HT(1A) receptors in cognitive processes playing a role in the development of depression such as impulsiveness or response to environmental stress. This exceptionally wide spectrum of effects is attributable to the presence of 5-HT1A receptors in serotonergic as well as other, for example glutamatergic, cholinergic, dopaminergic and noradrenergic neurons. The majority of the effects of 5-HT(1A) receptors is manifested via the mediation of Gi proteins through the hyperpolarisation or inhibition of the neuron carrying the receptor. 5-HT(1A) receptors on serotonergic neurons can be found in the somatodendritic area and play a significant role in delaying the effects of antidepressants which is an obvious disadvantage. Therefore the newest serotonergic antidepressants including vilazodone and vortioxetine have been designed to possess 5-HT(1A) receptor partial agonist properties. In the present paper we focus primarily on the role of 5-HT(1A) receptors in stress and

  2. Antidepressants Normalize the Default Mode Network in Patients With Dysthymia

    PubMed Central

    Posner, Jonathan; Hellerstein, David J.; Gat, Inbal; Mechling, Anna; Klahr, Kristin; Wang, Zhishun; McGrath, Patrick J.; Stewart, Jonathan W.; Peterson, Bradley S.

    2014-01-01

    Importance The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain’s DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown. Objective To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity. Design After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011. Setting University research institute. Participants Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex. Main Outcome Measures We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain’s DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity. Results Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain’s DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity

  3. Antidepressant-like action of the hydromethanolic flower extract of Tagetes erecta L. in mice and its possible mechanism of action

    PubMed Central

    Khulbe, Aarti; Pandey, Savita; Sah, Sangeeta Pilkhwal

    2013-01-01

    Objective: Tagetes erecta, the marigold, has commercial and ethnomedicinal use; however, reports concerning its efficacy for the treatment of depression are lacking. This study was carried out to elucidate the antidepressant effect of hydromethanolic flower extract of T. erecta. Materials and Methods: Hydromethanolic extract of flowers of Tagetes erecta was subjected to preliminary phytochemical screening. The extract (12.5, 25, and 50 mg/kg, i.p.) was evaluated for antidepressant effect using forced swim test in mice. The mechanism of antidepressant action was further examined using different drugs and imipramine was used as standard drug. Results: T. erecta significantly inhibited the immobility period in forced swim test in mice P<0.05). T. erecta (25 mg/kg, i.p.) enhanced the anti-immobility effect of antidepressant drugs like imipramine, fluoxetine, and p-chlorophenylalanine, an inhibitor of serotonin synthesis significantly attenuated its antidepressant effect. The antidepressant effect of T. erecta in the forced swim test was prevented by pretreatment with L-arginine and sildenafil, whereas pretreatment of mice with nitric oxide synthase inhibitors potentiated the action. Pentazocine, a high-affinity sigma receptor agonist, produced synergism with effective dose of T. erecta while progesterone, a sigma receptor antagonist, reversed the antidepressant effect of T. erecta. However, the locomotor activity was not affected at tested doses. Conclusions: Serotonergic, nitrergic pathway, and sigma receptors are possibly involved in mediating antidepressant action of T. erecta in mouse forced swim test. PMID:24014916

  4. LC-MS/MS method for the determination of nine antidepressants and some of their main metabolites in oral fluid and plasma. Study of correlation between venlafaxine concentrations in both matrices.

    PubMed

    de Castro, A; Concheiro, M; Quintela, O; Cruz, A; López-Rivadulla, M

    2008-09-10

    In this paper, a fast, sensitive and selective LC-MS/MS method is described for the simultaneous determination of amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine, as well as some of their main metabolites (nortriptyline, desipramine, norclomipramine and norfluoxetine), in oral fluid and plasma. The sample (0.2 mL) was extracted with an automated solid-phase extraction system (ASPEC XL), using mixed mode OASIS MCX cartridges. Chromatographic separation was performed in a Sunfire C18 IS column (20 mmx2.1 mm, 3.5 microm), using a gradient of acetonitrile and ammonium formate (pH 3; 2 mM) as mobile phase, which allowed the elution of all the compounds in less than 5 min. The method has been fully validated in both specimens. This method was initially applied to the analysis of oral fluid and plasma samples from patients on antidepressant treatment in order to assess for which compounds it was likely to find a good correlation between both matrices. The best results were obtained for venlafaxine, so the study was extended for this compound, comparing the ratio between oral fluid and plasma concentrations (ROF/PL) in five patients on venlafaxine treatment when both samples were collected simultaneously on four different occasions. An important inter and intraindividual variability was found in oral fluid concentrations for 150 mg dose (mean=287.5 ng/m, range 58.8-531.2 ng/mL) and for 75 mg dose (mean=186.3 ng/mL, range=82.1-289.2 ng/mL). R(OF/PL) was calculated for each patient on the four different occasions, showing also a high variability (CV=24.2-69.6%). PMID:18602787

  5. From Randomized Controlled Trials of Antidepressant Drugs to the Meta-Analytic Synthesis of Evidence: Methodological Aspects Lead to Discrepant Findings

    PubMed Central

    Fountoulakis, Konstantinos N.; McIntyre, Roger S.; Carvalho, André F.

    2015-01-01

    During the last decade, several meta-analytic studies employing different methodological approaches have had inconsistent conclusions regarding antidepressant efficacy. Herein, we aim to comment on methodological aspects that may have contributed to disparate findings. We initially discuss methodological inconsistencies and limitations related to the conduct of individual antidepressant randomized controlled trials (RCTs), including differences in allocated samples, limitations of psychometric scales, possible explanations for the heightened placebo response rates in antidepressant RCTs across the past two decades as well as the reporting of conflicts of interest. In the second part of this article, we briefly describe the various meta-analyses techniques (e.g., simple random effects meta-analysis and network meta-analysis) and the application of these methods to synthesize evidence related to antidepressant efficacy. Recently published antidepressant metaanalyses often provide discrepant results and similar results often lead to different interpretations. Finally, we propose strategies to improve methodology considering real-world clinical scenarios. PMID:26467410

  6. Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells.

    PubMed

    Wang, Yan; Hilton, Benjamin A; Cui, Kui; Zhu, Meng-Yang

    2015-08-01

    DNA damage is a form of cell stress and injury. Increased systemic DNA damage is related to the pathogenic development of neurodegenerative diseases. Depression occurs in a relatively high percentage of patients suffering from degenerative diseases, for whom antidepressants are often used to relieve depressive symptoms. However, few studies have attempted to elucidate why different groups of antidepressants have similar effects on relieving symptoms of depression. Previously, we demonstrated that neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)- and camptothecin (CPT) induced the DNA damage response in SH-SY5Y cells, and DSP4 caused cell cycle arrest which was predominately in the S-phase. The present study shows that CPT treatment also resulted in similar cell cycle arrest. Some classic antidepressants could reduce the DNA damage response induced by DSP4 or CPT in SH-SY5Y cells. Cell viability examination demonstrated that both DSP4 and CPT caused cell death, which was prevented by spontaneous administration of some tested antidepressants. Flow cytometric analysis demonstrated that a majority of the tested antidepressants protect cells from being arrested in S-phase. These results suggest that blocking the DNA damage response may be an important pharmacologic characteristic of antidepressants. Exploring the underlying mechanisms may allow for advances in the effort to improve therapeutic strategies for depression appearing in degenerative and psychiatric diseases. PMID:26038195

  7. Differential role of AMPA receptors in mouse tests of antidepressant and anxiolytic action.

    PubMed

    Andreasen, Jesper T; Fitzpatrick, Ciaran M; Larsen, Maria; Skovgaard, Lars; Nielsen, Simon D; Clausen, Rasmus P; Troelsen, Karin; Pickering, Darryl S

    2015-03-19

    Depression and anxiety often co-occur, and conventional monoamine-facilitating antidepressants show efficacy against symptoms in both disorders. Rodent studies indicate that antidepressant effects of monoamine-based antidepressants involve increased α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid glutamate receptor (AMPAR) neurotransmission, and positive allosteric modulators (PAMs) at AMPARs produced antidepressant-like effects in rodents. While this suggests that increased AMPAR-mediated neurotransmission is beneficial in depression management, preclinical studies addressing AMPARs in relation to anxiety have given ambiguous results with both anxiolytic-like and anxiogenic-like effects observed after AMPAR blockade. This study systematically compared the effects of the AMPAR potentiator LY451646 and the AMPAR antagonist GYKI-53655 on depression-related behaviour using the mouse forced swim (FST) and tail suspension tests (TST), and anxiety-related behaviour using the elevated zero maze (EZM), marble burying (MB) and novelty-induced hypophagia (NIH) tests. The serotonin-selective antidepressant citalopram was included for comparison. Due to the importance of AMPARs in learning and memory we also tested if GYKI-53655 disrupted performance in the V-maze test for attention-dependent behaviour, and the social transmission of food preference (STFP) test of long-term memory. LY451646 (3 mg/kg) showed an antidepressant-like profile in the FST and TST, and GYKI-53655 (≥ 5 mg/kg) had a depressogenic-like effect in the TST but no effect in the FST. Conversely, GYKI-53655 produced marked anxiolytic-like effects in the EZM (≥ 2.5 mg/kg), MBT (≥ 2.5 mg/kg), and NIH tests (≥ 5 mg/kg), while LY451646 (≥ 3 mg/kg) increased anxiety-like behaviour in the EZM. Citalopram showed an antidepressant-like effect in the FST (≥ 10 mg/kg), but not TST, an anxiolytic-like effect in the EZM (≥ 3 mg/kg) and MB test (≥ 2.5 mg/kg), and an anxiogenic-like effect in the NIH

  8. Treatment of anorexia nervosa with antidepressants.

    PubMed

    Hudson, J I; Pope, H G; Jonas, J M; Yurgelun-Todd, D

    1985-02-01

    Nine patients with anorexia nervosa were treated with antidepressant medications from three classes: tricyclics, monoamine oxidase inhibitors, and triazolopyridines. A tenth patient was treated with the combination of lithium carbonate and carbamazepine. With either the initial or a subsequent medication trial, four patients had displayed significant improvement in weight and in other anorexic and bulimic symptoms. Three additional patients had a marked or moderate improvement in bulimic symptoms, one with moderate and two without any weight gain. Two other patients had moderate weight gain. Side effects were a significant problem in many of the patients. These preliminary results suggest that antidepressants may be of benefit in the treatment of some patients with anorexia nervosa. PMID:3919068

  9. Antidepressant-Induced Female Sexual Dysfunction.

    PubMed

    Lorenz, Tierney; Rullo, Jordan; Faubion, Stephanie

    2016-09-01

    Because 1 in 6 women in the United States takes antidepressants and a substantial proportion of patients report some disturbance of sexual function while taking these medications, it is a near certainty that the practicing clinician will need to know how to assess and manage antidepressant-related female sexual dysfunction. Adverse sexual effects can be complex because there are several potentially overlapping etiologies, including sexual dysfunction associated with the underlying mood disorder. As such, careful assessment of sexual function at the premedication visit followed by monitoring at subsequent visits is critical. Treatment of adverse sexual effects can be pharmacological (dose reduction, drug discontinuation or switching, augmentation, or using medications with lower adverse effect profiles), behavioral (exercising before sexual activity, scheduling sexual activity, vibratory stimulation, psychotherapy), complementary and integrative (acupuncture, nutraceuticals), or some combination of these modalities. PMID:27594188

  10. [Neuroleptic malignant syndrome from treatment with antidepressives].

    PubMed

    Heinemann, F; Assion, H J; Laux, G

    1997-05-01

    The neuroleptic malignant syndrome (NMS) is a rare complication in the treatment of neuroleptics. The pathophysiology is not fully known. A dopaminergic transmission block in the basal ganglia and the hypothalamus is thought to be the pathophysiological mechanism of NMS. There are some findings against the single role of dopamine receptor blockade: NMS is rare under neuroleptic treatment, although a strong dopamine receptor blockade is found even with a low dosis of neuroleptics. NMS can develop even after longterm treatment with neuroleptics and is not improved by dopamine agonists within the expected period. NMS may even develop when neuroleptics are reduced. Several cases have been reported of NMS precipitated by medication without a direct effect on dopaminergic system. Only rare case reports describe NMS under antidepressants. We report on all cases of NMS associated with antidepressants and present the different pathophysiological hypotheses on the precipitation of NMS. PMID:9235312

  11. Antidepressant Drugs to Electroconvulsive Therapy: Kristina's Story.

    PubMed

    Sammons, Kristina M; Abraham, Sam

    2016-08-01

    A mother of three children experienced depression after each delivery. The worst bout occurred after the birth of her third child. Antidepressant drugs helped initially, but a change in dosage caused severe decompensating symptoms that resulted in feelings and thoughts that life is not worth living. Health care providers would not facilitate entry into an inpatient program for help. She was told that unless actively suicidal or homicidal, she could not be admitted to an inpatient unit. None of the prescribed antidepressant medications seemed to work and the physicians said there was nothing else they could do. Family and friends searched for help and found a psychiatrist who recommended electroconvulsive therapy. Kristina tells her story of experiencing depression and recovery. [Journal of Psychosocial Nursing and Mental Health Nursing, 54(8), 43-47.]. PMID:27479479

  12. [Vortioxetine: a new antidepressant to treat depressive episodes].

    PubMed

    Colle, R; Corruble, E

    2016-02-01

    Vortioxetine is a new antidepressant, which mechanism of action is multimodal, targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin transporter (5-HTT). Its efficacy and safety were assessed in fourteen studies including more than 3700 patients with a major depressive episode and treated with vortioxetine. In short-term studies (8 weeks), vortioxetine is more efficacious than placebo in decreasing depressive symptoms as measured by the MADRS total score, response rate (vortioxetine: 53.2% vs placebo: 35.2%) and remission rate (vortioxetine: 29.2% vs placebo: 19.3%). In a long-term study (52 weeks), vortioxetine is also superior to placebo in preventing relapses and recurrences. Moreover, in second line treatment, after failure of a first line selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrin reuptake inhibitor (SNRI), vortioxetine is superior to agomelatine in improving depressive symptoms and achieving response and remission. Furthermore, the positive effects of vortioxetine on improvement of cognitive symptoms of major depressive episodes are particularly well established in several clinical trials. The tolerability profile of vortioxetine is favourable. The recommended daily posology of vortioxetine is 10mg/d. Vortioxetine is a new antidepressant drug with a multimodal mechanism of action, well-documented efficacy and safety profiles. PMID:26358483

  13. [Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder].

    PubMed

    Tanaka, Teruaki; Inoue, Takeshi; Suzuki, Katsuji; Kitaichi, Yuji; Masui, Takuya; Denda, Kenzo; Koyama, Tsukasa

    2007-01-01

    Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to

  14. Hippocampal volume correlates with attenuated negative psychotic symptoms irrespective of antidepressant medication

    PubMed Central

    Bernasconi, Raffaele; Smieskova, Renata; Schmidt, André; Harrisberger, Fabienne; Raschle, Nora Maria; Lenz, Claudia; Walter, Anna; Simon, Andor; Riecher-Rössler, Anita; Radue, Ernst-Wilhelm; Lang, Undine E.; Fusar-Poli, Paolo; Borgwardt, Stefan J.

    2015-01-01

    Background Individuals with at-risk mental state for psychosis (ARMS) often suffer from depressive and anxiety symptoms, which are clinically similar to the negative symptomatology described for psychosis. Thus, many ARMS individuals are already being treated with antidepressant medication. Objectives To investigate clinical and structural differences between psychosis high-risk individuals with or without antidepressants. Methods We compared ARMS individuals currently receiving antidepressants (ARMS-AD; n = 18), ARMS individuals not receiving antidepressants (ARMS-nonAD; n = 31) and healthy subjects (HC; n = 24), in terms of brain structure abnormalities, using voxel-based morphometry. We also performed region of interest analysis for the hippocampus, anterior cingulate cortex, amygdala and precuneus. Results The ARMS-AD had higher ‘depression’ and lower ‘motor hyperactivity’ scores than the ARMS-nonAD. Compared to HC, there was significantly less GMV in the middle frontal gyrus in the whole ARMS cohort and in the superior frontal gyrus in the ARMS-AD subgroup. Compared to ARMS-nonAD, the ARMS-AD group showed more gray matter volume (GMV) in the left superior parietal lobe, but less GMV in the left hippocampus and the right precuneus. We found a significant negative correlation between attenuated negative symptoms and hippocampal volume in the whole ARMS cohort. Conclusion Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action. PMID:26110110

  15. Antidepressant Treatment and Suicide Attempts and Self-inflicted Injury in Children and Adolescents

    PubMed Central

    Gibbons, Robert D.; Perraillon, Marcelo Coca; Hur, Kwan; Conti, Rena M.; Valuck, Robert J.; Brent, David A.

    2014-01-01

    Purpose In 2004 FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5–17 treated with antidepressants in two large observational datasets taking account time-varying confounding. Methods We analyzed two large U.S. medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5–17) with new episodes of depression, with and without antidepressant treatment during the period of 2004–2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding. Results For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process, and revealed odds ratios close to 1.0, which were consistent with chance expectations. Conclusions The imbalance in both static and dynamic characteristics of patients in terms of the treatment selection process lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury. Use of MSM to adjust for dynamic treatment selection adjusts for this imbalance and may explain why some previous observational studies have found positive associations between antidepressant treatment and suicide and related behaviors in youth. PMID:25263479

  16. Safety and tolerability of the new antidepressants.

    PubMed

    Nelson, J C

    1997-01-01

    The newer serotonergic antidepressants have become popular particularly because of improved tolerability and safety. The evidence supporting this belief is reviewed. The factors that contribute to the development of somatic symptoms are examined, including the depression itself and the drugs used for treatment. The rates for individual side effects with the serotonin selective reuptake inhibitors, nefazodone, and venlafaxine are presented and compared with the adverse event experience for mirtazapine. PMID:9227670

  17. NMDA receptor subunits and associated signaling molecules mediating antidepressant-related effects of NMDA-GluN2B antagonism

    PubMed Central

    Kiselycznyk, Carly; Jury, Nicholas; Halladay, Lindsay; Nakazawa, Kazu; Mishina, Masayoshi; Sprengel, Rolf; Grant, Seth G.N.; Svenningsson, Per; Holmes, Andrew

    2015-01-01

    Drugs targeting the glutamate N-methyl-D-aspartate receptor (NMDAR) may be efficacious for treating mood disorders, as exemplified by the rapid antidepressant effects produced by single administration of the NMDAR antagonist ketamine. Though the precise mechanisms underlying the antidepressant-related effects of NMDAR antagonism remain unclear, recent studies implicate specific NMDAR subunits, including GluN2A and GluN2B, as well as the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) subunit glutamate receptor interacting molecule, PSD-95. Here, integrating mutant and pharmacological in mice, we investigated the contribution of these subunits and molecules to antidepressant-related behaviors and the antidepressant-related effects of the GluN2B blocker, Ro 25-6981. We found that global deletion of GluA1 or PSD-95 reduced forced swim test (FST) immobility, mimicking the antidepressant-related effect produced by systemically administered Ro 25-6981 in C57BL/6J mice. Moreover, the FST antidepressant-like effects of systemic Ro 25-6981 were intact in mutants with global GluA1 deletion or GluN1 deletion in forebrain interneurons, but were absent in mutants constitutively lacking GluN2A or PSD-95. Next, we found that microinfusing Ro 25-6981 into the medial prefrontal cortex (mPFC), but not basolateral amygdala, of C57BL/6J mice was sufficient to produce an antidepressant-like effect. Together, these findings extend and refine current understanding of the mechanisms mediating antidepressant-like effects produced by NMDAR-GluN2B antagonists, and may inform the development of a novel class of medications for treating depression that target the GluN2B subtype of NMDAR. PMID:25800971

  18. Neurochemical and metabolic aspects of antidepressants: an overview

    PubMed Central

    Baker, GB; Coutts, RT; Greenshaw, AJ

    2000-01-01

    Antidepressants, in addition to being effective therapeutic agents for depression, have also proved to be multifaceted drugs useful for treating a number of other psychiatric and neurologic disorders. Despite the widespread use of these drugs, much remains to be understood about their mechanisms of action and other important aspects, such as their metabolism and potential interactions with other drugs. This article reviews research conducted in the authors' laboratories on various aspects of antidepressants, including trace amines and antidepressants, gamma-aminobutyric acid and antidepressants, drug metabolism, development and application of rapid, sensitive assay procedures for antidepressants and their metabolites; and drug development based on analogues of the antidepressants phenelzine and tranylcypromine. The significance of this work to future drug development is also discussed. PMID:11109299

  19. Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients.

    PubMed

    Milanesi, Elena; Hadar, Adva; Maffioletti, Elisabetta; Werner, Haim; Shomron, Noam; Gennarelli, Massimo; Schulze, Thomas G; Costa, Marta; Del Zompo, Maria; Squassina, Alessio; Gurwitz, David

    2015-07-01

    Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 (IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression has been suggested as a putative biomarker for lithium unresponsiveness. In this study, we examined the in vitro effects of insulin-like growth factor 1 (IGF-1) on lithium sensitivity in lymphoblastoid cell lines (LCLs) from lithium responder (R) and non-responder (NR) bipolar patients. Moreover, we evaluated levels of microRNA let-7c, a small RNA predicted to target IGF1. We found that exogenous IGF-1 added to serum-free media increased lithium sensitivity selectively in LCLs from NR BD patients. However, no significant differences were observed when comparing let-7c expression in LCLs from R vs. NR BD patients. Our data support a key role for IGF-1 in lithium resistance/response in the treatment of bipolar disorder. PMID:25740013

  20. Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats.

    PubMed

    Rogóz, Zofia; Skuza, Grazyna; Maj, Jerzy; Danysz, Wojciech

    2002-06-01

    In spite of intensive research, the problem of treating antidepressant-resistant depressive patients has not yet been solved. The authors previously reported that combined administration of imipramine and the uncompetitive NMDA receptor antagonist amantadine reduced immobility time in the forced swimming test in rats to a much greater extent than either treatment alone. The present paper investigates the possibility of synergistic interactions between three antidepressants (imipramine, venlafaxine, fluoxetine) with three uncompetitive NMDA receptor antagonists (amantadine, memantine and neramexane). Most combinations resulted in synergistic (hyperadditive) antidepressive-like effects in the forced swim test. Most interesting was the observation that fluoxetine, which was inactive when given alone, showed a positive effect when combined with amantadine (10 and 20 mg/kg), memantine (2.5 and 5 mg/kg) or neramexane (2.5 and 5 mg/kg). The specificity of these observations is supported by control open field studies, which demonstrated no significant increase, or even a decrease in general locomotion after coadministration of the compounds. The present results suggest that the combination of traditional antidepressant drugs and NMDA receptor antagonists may produce enhanced antidepressive effects, and this is of particular relevance for antidepressant-resistant patients. PMID:12128003

  1. Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus

    PubMed Central

    Zhang, Hailou; Xue, Wenda; Wu, Runjie; Gong, Tong; Tao, Weiwei; Zhou, Xin; Jiang, Jingjing; Zhang, Ying; Zhang, Nan; Cui, Yi; Chen, Chang; Chen, Gang

    2015-01-01

    Ethanol extract of Yueju pill, a Traditional Chinese Medicine herbal formula widely used to treat mood disorders, demonstrates rapid antidepressant effects similar to ketamine, likely via instant enhancement of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Here we investigated ethanol extracts of the constituent herbs of Yueju responsible for rapid antidepressant effects. Screening with tail suspension test in Kunming mice at 24 hours after a single administration of five individual constituent herbs of Yueju, we found that only Gardenia jasminoides Ellis (GJ) showed a significant effect. The antidepressant response started at 2 hours after GJ administration. Similar to Yueju and ketamine, a single administration of GJ significantly reduced the number of escape failures in the learned helplessness test. Furthermore, GJ decreased latency of food consumption in the novelty suppressed-feeding test. Additionally, starting from 2 hours and continuing for over 20 hours after GJ administration, BDNF expression in the hippocampus was upregulated, temporally linked with the antidepressant response. These findings suggest that GJ has rapid antidepressant effects, which are associated with the elevated expression of BDNF in the hippocampus. In Yueju formula, Yue represents GJ, as thus our study demonstrates the primary role of GJ in rapid antidepressant efficacy of Yueju. PMID:25878718

  2. Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus.

    PubMed

    Zhang, Hailou; Xue, Wenda; Wu, Runjie; Gong, Tong; Tao, Weiwei; Zhou, Xin; Jiang, Jingjing; Zhang, Ying; Zhang, Nan; Cui, Yi; Chen, Chang; Chen, Gang

    2015-01-01

    Ethanol extract of Yueju pill, a Traditional Chinese Medicine herbal formula widely used to treat mood disorders, demonstrates rapid antidepressant effects similar to ketamine, likely via instant enhancement of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Here we investigated ethanol extracts of the constituent herbs of Yueju responsible for rapid antidepressant effects. Screening with tail suspension test in Kunming mice at 24 hours after a single administration of five individual constituent herbs of Yueju, we found that only Gardenia jasminoides Ellis (GJ) showed a significant effect. The antidepressant response started at 2 hours after GJ administration. Similar to Yueju and ketamine, a single administration of GJ significantly reduced the number of escape failures in the learned helplessness test. Furthermore, GJ decreased latency of food consumption in the novelty suppressed-feeding test. Additionally, starting from 2 hours and continuing for over 20 hours after GJ administration, BDNF expression in the hippocampus was upregulated, temporally linked with the antidepressant response. These findings suggest that GJ has rapid antidepressant effects, which are associated with the elevated expression of BDNF in the hippocampus. In Yueju formula, Yue represents GJ, as thus our study demonstrates the primary role of GJ in rapid antidepressant efficacy of Yueju. PMID:25878718

  3. Improving Access to Psychological Therapies and antidepressant prescribing rates in England: a longitudinal time-series analysis

    PubMed Central

    Sreeharan, Vaishnavee; Madden, Hugo; Lee, John Tayu; Millett, Christopher; Majeed, Azeem

    2013-01-01

    Background Antidepressant prescribing rates in England have been increasing since the 1970s. The impact of the Improving Access to Psychological Therapies (IAPT) initiative on antidepressant prescribing rates is unknown. Aim To investigate the impact of the establishment of IAPT services on antidepressant prescribing rates in primary care trusts (PCTs) in England. Design and setting A longitudinal time-series analysis, using PCT-level data from 2008 to 2011 set in England. Method A time-series analysis was conducted using PCT-level prescription data, dates of establishment of IAPT services, and covariate data for age, sex, and socioeconomic status. Statistical analysis was carried out using analysis of variance and a random-effect negative binomial model. Results Antidepressant prescribing rates in England increased by 10% per year during the study period (adjusted rate ratio = 1.10, 95% CI = 1.09 to 1.10). The implementation of IAPT services had no significant effect on antidepressant prescribing (adjusted rate ratio = 0.99, 95% CI = 0.99 to 1.00). Conclusion Introduction of a large-scale initiative to increase provision of psychological therapies has not curbed the long-term increased prescribing of antidepressants in England. PMID:23998846

  4. Antidepressant medication can improve hypertension in elderly patients with depression.

    PubMed

    Fu, Wenjing; Ma, Lina; Zhao, Xiaoling; Li, Yun; Zhu, Hong; Yang, Wei; Liu, Chuan; Liu, Jia; Han, Rui; Liu, Huizhen

    2015-12-01

    We explored the influence of antidepressant therapy on blood pressure and quality of life in elderly patients with hypertension. Depression occurs at a higher rate in patients with hypertension than in the normal population. It has been reported that depressive symptoms lead to poorer hypertension control, resulting in the development of complications. We conducted a randomized, parallel group study. A total of 70 elderly patients with hypertension in the period of August 2008 to March 2011 were divided into two groups based on their antihypertensive therapy, a control group (amlodipine, 5 mg daily; n=35) and a therapy group (amlodipine, 5mg daily; citalopram, 20 mg daily; n=35). We compared 24 hour, daytime, and nighttime measurements of systolic and diastolic blood pressure, in addition to quality of life, assessed using the Hamilton rating scale for depression, and a 36 item Short Form quality of life questionnaire (SF-36). Both groups were followed for 3 months. At the end of 3 months, all blood pressure levels were significantly lower in the therapy group than in the control group. The other scores (with the exception of the physical function subcategory of the SF-36 quality of life scale) were significantly higher. Our study indicates that clinicians should be aware of depressive symptoms in elderly patients with hypertension, and should consider antidepressant therapy in these patients. PMID:26256065

  5. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis.

    PubMed

    Beiske, Georg Anton Giæver; Holmøy, Trygve; Beiske, Antonie Giæver; Johannessen, Svein I; Johannessen Landmark, Cecilie

    2015-01-01

    Objective. Patients with multiple sclerosis (MS) are often suffering from neuropathic pain. Antiepileptic drugs (AEDs) and tricyclic antidepressants (TCAs) are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females) with mean age of 53 (±10) years and EDSS 4.8 (±1.7) used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6%) or amitriptyline (9.7%). Polypharmacy was widespread (mean 5.4 drugs) with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects. PMID:26221541

  6. Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons

    PubMed Central

    Beckmann, Nadine; Sharma, Deepa; Gulbins, Erich; Becker, Katrin Anne; Edelmann, Bärbel

    2014-01-01

    Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM) was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer's disease, and major depression, as well as viral (e.g., measles virus) and bacterial (e.g., Staphylococcus aureus, Pseudomonas aeruginosa) infections. Ceramide molecules may act in these diseases by the alteration of membrane biophysics, the self-association of ceramide molecules within the cell membrane and the ultimate formation of larger ceramide-enriched membrane domains/platforms. These domains were shown to serve the clustering of certain receptors such as CD95 and may also act in the above named diseases. The potential to block the generation of ceramide by inhibiting the ASM has opened up new therapeutic approaches for the treatment of these conditions. Since amitriptyline is one of the longest used clinical drugs and side effects are well studied, it could potentially become a cheap and easily accessible medication for patients suffering from these diseases. In this review, we aim to provide an overview of current in vitro and in vivo studies and clinical trials utilizing amitriptyline to inhibit ASM and contemplate possible future applications of the drug. PMID:25228885

  7. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

    PubMed Central

    Beiske, Georg Anton Giæver; Holmøy, Trygve; Beiske, Antonie Giæver; Johannessen, Svein I.; Johannessen Landmark, Cecilie

    2015-01-01

    Objective. Patients with multiple sclerosis (MS) are often suffering from neuropathic pain. Antiepileptic drugs (AEDs) and tricyclic antidepressants (TCAs) are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females) with mean age of 53 (±10) years and EDSS 4.8 (±1.7) used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6%) or amitriptyline (9.7%). Polypharmacy was widespread (mean 5.4 drugs) with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects. PMID:26221541

  8. S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders

    PubMed Central

    Feld, Jordan J.; Modi, Apurva A.; El-Diwany, Ramy; Rotman, Yaron; Thomas, Emmanuel; Koh, Christopher; Cherepanov, Vera; Heller, Theo; Ghany, Marc G.; Park, Yoon; Hoofnagle, Jay H.; Liang, T. Jake

    2010-01-01

    Background & Aims Fewer than half of patients infected with Hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon and ribavirin therapy. S-adenosyl methionine (SAMe) increases interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early anti-viral response and interferon signaling in patients that did not respond to previous therapy (nonresponders) and investigated its mechanisms. Methods Nonresponders with HCV genotype-1 were given 2 weeks of peginterferon alfa-2a and ribavirin (Course A, baseline/control). After a 1-month period, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (Course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. Results The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar before and after administration of SAMe. However, the slope increased for the second-phase decrease in HCV between courses A and B (Course A=0.11±0.04 log10IU/mL/week, Course B=0.27±0.06; P=0.009); 11 patients (53%) achieved an early virological response and 10 (48%) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater after Course B. In cultured cells, SAMe increased induction of ISGs, compared with only peginterferon and ribavirin, and the antiviral effects of interferon by increasing STAT1 methylation, which might promote binding of STAT1 to DNA. Conclusions The addition of SAMe to peginterferon and ribavirin improves the kinetics of the early anti-viral response and induces ISGs in patients with HCV genotype 1 that do not respond to interferon therapy. SAMe might be used with peginterferon-based therapies in patients with chronic HCV infections. PMID:20854821

  9. The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor potentiator LY 451646 are preserved in bdnf⁺/⁻ heterozygous null mice.

    PubMed

    Lindholm, Jesse S O; Autio, Henri; Vesa, Liisa; Antila, Hanna; Lindemann, Lothar; Hoener, Marius C; Skolnick, Phil; Rantamäki, Tomi; Castrén, Eero

    2012-01-01

    Accumulating evidence suggests that biogenic amine-based antidepressants act, at least in part, via regulation of brain-derived neurotrophic factor (BDNF) signaling. Biogenic amine-based antidepressants increase BDNF synthesis and activate its signaling pathway through TrkB receptors. Moreover, the antidepressant-like effects of these molecules are abolished in BDNF deficient mice. Glutamate-based drugs, including the NMDA antagonist ketamine, and the AMPA receptor potentiator LY 451646, mimic the effects of antidepressants in preclinical tests with high predictive validity. In humans, a single intravenous dose of ketamine produces an antidepressant effect that is rapid, robust and persistent. In this study, we examined the role of BDNF in expression of the antidepressant-like effects of ketamine and an AMPA receptor potentiator (LY 451646) in the forced swim test (FST). Ketamine and LY 451646 produced antidepressant-like effects in the FST in mice at 45 min after a single injection, but no effects were observed one week after a single ketamine injection. As previously reported, the effects of imipramine in the forced swim test were blunted in heterozygous BDNF knockout (bdnf(+/-)) mice. However ketamine and LY 451646 produced similar antidepressant-like responses in wildtype and bdnf(+/-) mice. Neither ketamine nor LY 451646 significantly influenced the levels BDNF or TrkB phosphorylation in the hippocampus when assessed at 45 min or 7 days after the drug administration. These data demonstrate that under the conditions tested, neither ketamine nor the AMPA-potentiator LY 451656 activate BDNF signaling, but produce a characteristic antidepressant-like response in heterozygous bdnf(+/-) mice. These data indicate that unlike biogenic amine-based agents, BDNF signaling does not play a pivotal role in the antidepressant effects of glutamate-based compounds. This article is part of a Special Issue entitled 'Anxiety and Depression'. PMID:21867718

  10. Antidepressant pharmaceuticals in two U.S. effluent-impacted streams: Occurrence and fate in water and sediment and selective uptake in fish neural tissue

    USGS Publications Warehouse

    Schultz, M.M.; Furlong, E.T.; Kolpin, D.W.; Werner, S.L.; Schoenfuss, H.L.; Barber, L.B.; Blazer, V.S.; Norris, D.O.; Vajda, A.M.

    2010-01-01

    Antidepressant pharmaceuticals are widely prescribed in the United States; release of municipal wastewater effluent is a primary route introducing them to aquatic environments, where little is known about their distribution and fate. Water, bed sediment, and brain tissue from native white suckers (Catostomus commersoni)were collected upstream and atpoints progressively downstream from outfalls discharging to two effluentimpacted streams, Boulder Creek (Colorado) and Fourmile Creek (Iowa). A liquid chromatography/tandem mass spectrometry method was used to quantify antidepressants, including fluoxetine, norfluoxetine (degradate), sertraline, norsertraline (degradate), paroxetine, Citalopram, fluvoxamine, duloxetine, venlafaxine, and bupropion in all three sample matrices. Antidepressants were not present above the limit of quantitation in water samples upstream from the effluent outfalls but were present at points downstream at ng/L concentrations, even at the farthest downstream sampling site 8.4 km downstream from the outfall. The antidepressants with the highest measured concentrations in both streams were venlafaxine, bupropion, and Citalopram and typically were observed at concentrations of at least an order of magnitude greater than the more commonly investigated antidepressants fluoxetine and sertraline. Concentrations of antidepressants in bed sediment were measured at ng/g levels; venlafaxine and fluoxetine were the predominant chemicals observed. Fluoxetine, sertraline, and their degradates were the principal antidepressants observed in fish brain tissue, typically at low ng/g concentrations. Aqualitatively different antidepressant profile was observed in brain tissue compared to streamwater samples. This study documents that wastewater effluent can be a point source of antidepressants to stream ecosystems and that the qualitative composition of antidepressants in brain tissue from exposed fish differs substantially from the compositions observed in

  11. Secondary Metabolites from Three Florida Sponges with Antidepressant Activity

    PubMed Central

    Kochanowska, Anna J.; Rao, Karumanchi V.; Childress, Suzanne; El-Alfy, Abir; Matsumoto, Rae R.; Kelly, Michelle; Stewart, Gina S.; Sufka, Kenneth J.; Hamann, Mark T.

    2016-01-01

    Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were evaluated in the Porsolt forced swim test (FST) and the chick anxiety–depression continuum model. Among the isolated compounds, 5,6-dibromo-N,N-dimethyltryptamine (1) exhibited significant antidepressant-like action in the rodent FST model, while 5-bromo-N,N-dimethyltryptamine (2) caused significant reduction of locomotor activity indicative of a potential sedative action. The current study provides ample evidence that marine natural products with the diversity of brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs. PMID:18217716

  12. Antidepressants in the treatment of attention-deficit/hyperactivity disorder.

    PubMed

    Popper, C W

    1997-01-01

    Antidepressants differ in their effectiveness for treating attention-deficit/hyperactivity disorder (ADHD) in adults and children. None are as effective as psychostimulants for treating the attentional and cognitive symptoms, but they can help reduce impulsive and hyperactive behavior. Tricyclic antidepressants have well-demonstrated efficacy in treating behavioral symptoms, but desipramine should be avoided, at least in youths and adolescents (and perhaps adults), because safer tricyclics are available. Bupropion was effective in its few controlled trials, but tics and (especially in youth) skin rash limit its value. Venlafaxine appears effective, but controlled studies are needed. Serotonin selective reuptake inhibitors have not been tested in controlled trials, but they cause inconsistent changes, often aggravate ADHD symptoms, and can cause frontal apathy and disinhibition. Clonidine has not been adequately examined but seems to have small or uncertain effects. Psychostimulants remain the treatment of choice because of their unique effect on attention. Multimodal treatments (medications plus psychosocial) might not be more effective than medications alone. PMID:9418743

  13. Plasma insulin-like growth factor I levels are higher in depressive and anxiety disorders, but lower in antidepressant medication users.

    PubMed

    Bot, Mariska; Milaneschi, Yuri; Penninx, Brenda W J H; Drent, Madeleine L

    2016-06-01

    It has been postulated that many peripheral and (neuro)biological systems are involved in psychiatric disorders such as depression. Some studies found associations of depression and antidepressant treatment with insulin-like growth factor 1 (IGF-I) - a pleiotropic hormone affecting neuronal growth, survival and plasticity - but evidence is mixed. We therefore studied whether depressive and anxiety disorders were associated with plasma IGF-I, and explored the role of antidepressant medication in this association in a large observational study. The sample consisted of 2714 participants enrolled in The Netherlands Study of Depression and Anxiety, classified as healthy controls (n=602), antidepressant users (76 remitted and 571 with current depressive and/or anxiety disorder(s), n=647), persons having remitted depressive and/or anxiety disorder(s) without antidepressant use (n=502), and persons having current depressive and/or anxiety disorder(s) without antidepressant use (n=963). Associations with IGF-I concentrations were studied and adjusted for socio-demographic, health, and lifestyle variables. Relative to healthy controls, antidepressant-free individuals with current disorders had significantly higher IGF-I levels (Cohen's d=0.08, p=0.006), whereas antidepressant-free individuals with remitted disorders had a trend towards higher IGF-I levels (d=0.06, p=0.09). Associations were evident for depressive and for anxiety disorders. In contrast, antidepressant users had significantly lower IGF-I levels compared to healthy controls (d=-0.08, p=0.028). Our findings suggests that antidepressant medication use modifies the association between depressive/anxiety disorders and plasma IGF-I. These results corroborate with findings of some previous small-scale case-control and intervention studies. The higher IGF-I levels related to depression and anxiety might point to a compensatory mechanism to counterbalance the impaired neurogenesis, although future studies are needed to

  14. Impact of combined treatment with rosuvastatin and antidepressants on liver and kidney function in rats

    PubMed Central

    HERBET, MARIOLA; GAWROŃSKA-GRZYWACZ, MONIKA; IZDEBSKA, MAGDALENA; PIĄTKOWSKA-CHMIEL, IWONA; JAGIEŁŁO-WÓJTOWICZ, EWA

    2016-01-01

    Depression is among the most prevalent and life-threatening forms of mental illness, and is also a risk factor for cardiovascular disorders, diabetes and metabolic syndrome. Elderly patients commonly receive statins for the prevention of cardiovascular diseases, and antidepressant drugs for the treatment of depression. It should be noted that long-term polypharmacotherapy may lead to potential drug interactions and disorders of the organs. The aim of the present study was to determine whether, and to what extent, combined treatment with rosuvastatin and antidepressants (amitriptyline or fluoxetine) influences the biochemical markers of liver and kidney function in a rat model. For this purpose, the activity levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and the concentrations of total protein, urea, creatinine and β2-microglobulin were determined. The results of the study indicated that combined treatment with rosuvastatin and the antidepressants amitriptyline and fluoxetine for 14 days altered the activity levels of ALT and GGT, and the concentrations of urea and creatinine in the serum compared with groups of rats receiving rosuvastatin or either antidepressant alone. These observed changes in biochemical parameters may suggest the possibility of impaired liver and kidney function during the continuous combined exposure to the drugs. However, further clinical and animal studies are required in order to further elucidate this process. PMID:27073465

  15. Neural correlates of antidepressant-related sexual dysfunction: a placebo-controlled fMRI study on healthy males under subchronic paroxetine and bupropion.

    PubMed

    Abler, Birgit; Seeringer, Angela; Hartmann, Antonie; Grön, Georg; Metzger, Coraline; Walter, Martin; Stingl, Julia

    2011-08-01

    Sexual dysfunction is a common side effect of selective serotonin reuptake inhibitors (SSRIs) like paroxetine in the treatment of depression, imposing a considerable risk on medication adherence and hence therapeutic success. Bupropion, a norepinephrine and dopamine reuptake inhibitor, is recommended as an alternative treatment without adverse effects concerning sexual arousal and libido. We investigated the neural bases of paroxetine-related subjective sexual dysfunction when compared with bupropion and placebo. We scanned 18 healthy, heterosexual males in a randomized, double-blind, within-subject design while watching video clips of erotic and nonerotic content under steady-state conditions after taking 20 mg of paroxetine, 150 mg of bupropion, and placebo for 7 days each. Under paroxetine, ratings of subjective sexual dysfunction increased compared with placebo or bupropion. Activation along the anterior cingulate cortex (ACC), including subgenual, pregenual, and midcingulate cortices, in the ventral striatum and midbrain was decreased when compared with placebo. In contrast, bupropion let subjective ratings and ACC activations unchanged and increased activity of brain regions including posterior midcingulate cortex, mediodorsal thalamus, and extended amygdala relative to placebo and paroxetine. Brain regions that have been related to the processing of motivational (ventral striatum), emotional, and autonomic components of erotic stimulation (anterior cingulate) in previous studies showed reduced responsiveness under paroxetine in our study. Drug effects on these regions may be part of the mechanism underlying SSRI-related sexual dysfunction. Increased activation under bupropion may point to an opposite effect that may relate to the lack of impaired sexual functioning. PMID:21544071

  16. Do Menopausal Status and Use of Hormone Therapy Affect Antidepressant Treatment Response? Findings from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study

    PubMed Central

    Toups, Marisa; Rush, A. John; Wisniewski, Stephen R.; Thase, Michael E.; Luther, James; Warden, Diane; Fava, Maurizio; Trivedi, Madhukar H.

    2013-01-01

    Abstract Background Menopausal status and use of hormonal contraception or menopausal hormone therapy (HT) may affect treatment response to selective serotonin reuptake inhibitors (SSRIs). This report evaluates whether menopausal status and use of hormonal contraceptives or menopausal HT affect outcome in women treated with citalopram. Methods In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 896 premenopausal and 544 postmenopausal women were treated with citalopram for 12–14 weeks. Baseline demographic and clinical characteristics were used in adjusted analysis of the effect of menopausal status and use of hormonal contraceptives or menopausal HT on outcomes. Remission was defined as final Hamilton Rating Scale for Depression-17 (HRSD17) ≤7 or Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) score ≤5 and response as ≥50% decrease from the baseline QIDS-SR16 score. Results Premenopausal and postmenopausal women differed in multiple clinical and demographic baseline variables but did not differ in response or remission rates. Premenopausal women taking hormonal contraceptives had significantly greater unadjusted remission rates on the HRSD17 and the QIDS-SR16 than women not taking contraception. Response and remission rates were not different between postmenopausal women taking vs. not taking HT. Adjusted results showed no significant difference in any outcome measure across menopause status in women who were not taking contraception/HT. There were no significant differences in adjusted results across HT status in premenopausal or postmenopausal women. Conclusions In this study, citalopram treatment outcome was not affected by menopausal status. Hormonal contraceptives and HT also did not affect probability of good outcome. PMID:23398127

  17. Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study.

    PubMed

    Wemakor, Anthony; Casson, Karen; Garne, Ester; Bakker, Marian; Addor, Marie-Claude; Arriola, Larraitz; Gatt, Miriam; Khoshnood, Babak; Klungsoyr, Kari; Nelen, Vera; O'Mahoney, Mary; Pierini, Anna; Rissmann, Anke; Tucker, David; Boyle, Breidge; de Jong-van den Berg, Lolkje; Dolk, Helen

    2015-11-01

    Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors. PMID:26148560

  18. Cardiovascular and cerebrovascular risk factors and events associated with second-generation antipsychotic compared to antidepressant use in a non-elderly adult sample: results from a claims-based inception cohort study

    PubMed Central

    Correll, Christoph U; Joffe, Benjamin I; Rosen, Lisa M; Sullivan, Timothy B; Joffe, Russell T

    2015-01-01

    This is a study of the metabolic and distal cardiovascular/cerebrovascular outcomes associated with the use of second-generation antipsychotics (SGAs) compared to antidepressants (ADs) in adults aged 18-65 years, based on data from Thomson Reuters MarketScan® Research Databases 2006-2010, a commercial U.S. claims database. Interventions included clinicians' choice treatment with SGAs (allowing any comedications) versus ADs (not allowing SGAs). The primary outcomes of interest were time to inpatient or outpatient claims for the following diagnoses within one year of SGA or AD discontinuation: hypertension, ischemic and hypertensive heart disease, cerebrovascular disease, diabetes mellitus, hyperlipidemia, and obesity. Secondary outcomes included the same diagnoses at last follow-up time point, i.e., not censoring observations at 365 days after SGA or AD discontinuation. Cox regression models, adjusted for age, gender, diagnosis of schizophrenia and mood disorders, and number of medical comorbidities, were run. Among 284,234 individuals, those within one year of exposure to SGAs versus ADs showed a higher risk of essential hypertension (adjusted hazard ratio, AHR+1.16, 95% CI: 1.12-1.21, p<0.0001), diabetes mellitus (AHR+1.43, CI: 1.33-1.53, p<0.0001), hypertensive heart disease (AHR+1.34, CI: 1.10-1.63, p<0.01), stroke (AHR+1.46, CI: 1.22-1.75, p<0.0001), coronary artery disease (AHR+1.17, CI: 1.05-1.30, p<0.01), and hyperlipidemia (AHR+1.12, CI: 1.07-1.17, p<0.0001). Unrestricted follow-up results were consistent with within one-year post-exposure results. Increased risk for stroke with SGAs has previously only been demonstrated in elderly patients, usually with dementia. This study documents, for the first time, a significantly increased risk for stroke and coronary artery disease in a non-elderly adult sample with SGA use. We also confirm a significant risk for adverse metabolic outcomes. These findings raise concerns about the longer-term safety of SGAs, given

  19. An open-label pilot study of aripiprazole for male and female veterans with chronic post-traumatic stress disorder who respond suboptimally to antidepressants.

    PubMed

    Youssef, Nagy A; Marx, Christine E; Bradford, Daniel W; Zinn, Sandra; Hertzberg, Michael A; Kilts, Jason D; Naylor, Jennifer C; Butterfield, Marian I; Strauss, Jennifer L

    2012-07-01

    Emerging data suggest that second-generation antipsychotics such as aripiprazole may be effective in the treatment of post-traumatic stress disorder (PTSD). However, few clinical trials have used aripiprazole in PTSD, and data are limited on its use in Veterans with PTSD. The objective of this pilot trial was to investigate the safety and efficacy of aripiprazole in Veterans with PTSD. Ten individuals (five men and five women) meeting the Diagnostic and statistical manual of mental disorders, 4th ed., PTSD criteria participated in this 12-week, open-label, flexibly dosed monotherapy trial. The dose range of aripiprazole was 5-30 mg/day, titrated to tolerability and clinical response. The primary outcome measure was the Clinician-Administered PTSD Scale. Additional outcomes included the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale (Top-8), the Davidson Trauma Scale, the Positive and Negative Syndrome Scale, the Beck Depression Inventory-Fast Screen, and Clinical Global Impressions-Improvement. Eight participants completed the study, and aripiprazole was generally well tolerated and associated with a significant improvement in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale (primary outcome measure) and by the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale, and the Davidson Trauma Scale. An improvement was also observed on all three Positive and Negative Syndrome Scale subscales and the Beck Depression Inventory-Fast Screen, and the average Clinical Global Impressions-Improvement ratings indicated that patients were 'much improved'. These promising initial results merit further investigation in a larger, randomized-controlled trial. PMID:22475888

  20. A case study comparing a randomized withdrawal trial and a double-blind long-term trial for assessing the long-term efficacy of an antidepressant.

    PubMed

    Mallinckrodt, Craig; Chuang-Stein, Christy; McSorley, Paul; Schwartz, Jeffrey; Archibald, Donald G; Perahia, David G; Detke, Michael J; Alphs, Larry

    2007-01-01

    Assessing long-term efficacy in psychiatric drugs involves a number of complex questions, and the priaority of these questions is different for different disorders and for different stakeholders. Therefore, it is essential that we not adopt a one-method-fits-all approach, but rather adapt the specific details of the designs and analysis of data from long-term trials to individual disease states. Randomized withdrawal (RW) designs, even though addressing a specific question of particular interest, face some difficult methodological and ethical challenges. A less common alternative design, termed the double-blind long-term efficacy (DBLE) design, is logistically similar to traditional responder extension designs. However, use of an analytic approach that includes all randomized patients rather than only the selected subset that continued beyond acute treatment avoids the major criticism of the extender design. The present paper illustrates the attributes of the RW and DBLE designs by analyzing data from trials adopting these designs. The RW and DBLE designs address different questions, and are thus not directly comparable. Potential benefits of the DBLE design include: (1) the parsimonious use of patients and the resultant reduced exposure to placebo as each patient can contribute to multiple developmental objectives; (2) the results are generalizable to actual clinical practice as the design matches treatment guidelines; and, (3) results of safety assessments are meaningful as they involve all randomized patients. Our case study suggests that the DBLE design can provide definitive answers to important questions and may be a useful design for assessing long-term treatment effects. PMID:17238129

  1. Successful antidepressant chronotherapeutics enhance fronto-limbic neural responses and connectivity in bipolar depression.

    PubMed

    Vai, Benedetta; Poletti, Sara; Radaelli, Daniele; Dallaspezia, Sara; Bulgarelli, Chiara; Locatelli, Clara; Bollettini, Irene; Falini, Andrea; Colombo, Cristina; Smeraldi, Enrico; Benedetti, Francesco

    2015-08-30

    The identification of antidepressant response predictors in bipolar disorder (BD) may provide new potential enhancements in treatment selection. Repeated total sleep deprivation combined with light therapy (TSD+LT) can acutely reverse depressive symptoms and has been proposed as a model antidepressant treatment. This study aims at investigating the effect of TSD+LT on effective connectivity and neural response in cortico-limbic circuitries during implicit processing of fearful and angry faces in patients with BD. fMRI and Dynamic Causal Modeling (DCM) were combined to study the effect of chronotherapeutics on neural responses in healthy controls (HC, n = 35) and BD patients either responder (RBD, n = 26) or non responder (nRBD, n = 11) to 3 consecutive TSD+LT sessions. Twenty-four DCMs exploring connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), Amygdala (Amy), fusiform gyrus and visual cortex were constructed. After treatment, patients significantly increased their neural responses in DLPFC, ACC and insula. nRBD showed lower baseline and endpoint neural responses than RBD. The increased activity in ACC and in medial prefrontal cortex, associated with antidepressant treatment, was positively associated with the improvement of depressive symptomatology. Only RBD patients increased intrinsic connectivity from DLPFC to ACC and reduced the modulatory effect of the task on Amy-DLPFC connection. A successful antidepressant treatment was associated with an increased functional activity and connectivity within cortico-limbic networks, suggesting the possible role of these measures in providing possible biomarkers for treatment efficacy. PMID:26195295

  2. Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

    PubMed Central

    Baek, Song-Eun; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Rho, Dae-Young; Kim, Do-Hoon; Huh, Sun

    2016-01-01

    Objective This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method. Methods Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later. Results There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups. Conclusion These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA. PMID:27081384

  3. Potential antidepressant properties of cysteamine on hippocampal BDNF levels and behavioral despair in mice.

    PubMed

    Shieh, Chu-Hsin; Hong, Chen-Jee; Huang, Yn-Ho; Tsai, Shih-Jen

    2008-08-01

    Several studies have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels, suggesting that BDNF signaling is important for the therapeutic mechanism of antidepressants. Recent work has found that cysteamine and its related agent, cystamine, are neuroprotective in Huntington's disease mice, and act by enhancing the secretion of central BDNF. In the present study, the potential antidepressant effects of cysteamine were examined by behavioral paradigms and biochemical assay. Male BALB/CByJ mice were given a single dose of normal saline, 10 mg/kg of imipramine or either 50, 100 or 200 mg/kg of cysteamine (i.p.) 30 min before undergoing the forced-swimming test (FST) or the tail suspension test (TST). Other groups of mice treated with the same drugs and doses, without behavioral tests, were sacrificed for hippocampal BDNF measurements. We found that, compared with the control group, the cysteamine 200-mg/kg group showed a significant reduction in immobility time in the FST (P<0.01) and TST (P<0.01), and showed lower activity in the open field test (P<0.01). A significant increase in hippocampal BDNF levels was found in the cysteamine 200-mg/kg group (P<0.05). Our findings suggested that cysteamine may possess an antidepressant-like effect, which may be mediated by increasing central BDNF levels. PMID:18582526

  4. Evolution of the concepts of the molecular mechanism of the action of antidepressants (survey)

    SciTech Connect

    Mashkovskii, M.D.; Andreeva, N.I.

    1986-09-01

    The authors discuss investigation devoted to the study of the mechanisms of the action of antidepressants. Under the conditions of an acute experiment, antidepressants exhibit high affinity for the binding sites of (/sup 3/H) WB 4101, (/sup 3/H) LSD, and (/sup 3/H) spiroperiodol (alpha/sub 1/- and S/sub 2/-receptors). Certain antidepressants also have a high affinity for the binding sites of (/sup 3/H) clonidine and (/sup 3/H) S (alpha/sub 2/- and S/sub 1/-receptors). When the method of binding of radioligands was used to study the receptors, it was found that stimulation of cAMP synthesis, induced by norepinephrine, is primarily a beta-adrenergic response. Investigations of the influence of antidepressants in the case of their acute action in vitro on serotonin receptors showed that they inhibit the binding of (/sup 3/H) LSD and (/sup 3/H) spiroperiodol in the rat brain with high affinity and the binding of (/sup 3/H) S with low affinity.

  5. Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis

    PubMed Central

    Guy, Stacey; Lam, Tracey; Teasell, Robert; Loh, Eldon

    2015-01-01

    Objective: To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI). Methods: A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with ≥3 individuals and ≥50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen’s d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted. Results: Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 ± 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group. Conclusion: The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required. PMID:26364286

  6. Additive antidepressant-like effects of fasting with imipramine via modulation of 5-HT2 receptors in the mice.

    PubMed

    Li, Bingjin; Zhao, Jing; Lv, Jiayin; Tang, Fang; Liu, Lei; Sun, Zhihui; Wang, Liang; Siwela, Sibongile P; Wang, Yinuo; Song, Yunong; Manchishi, Stephen M; Cui, Ranji

    2014-01-01

    Recently, studies show that intermittent fasting and caloric restriction may improve symptoms of depression. However, there is little scientific evidence regarding the literature on the antidepressant-like effects of acute fasting. The present study aims to investigate the antidepressant-like effects and its influence on brain levels of the transcription factor cAMP response element-binding protein (CREB) and its phosphorylated form (p-CREB) in different time periods of fasting mice. Furthermore, the additive antidepressant-like effects of fasting with imipramine and the possible involvement of the 5-HT2 receptors were examined. In the present study 9h, but not 3h and 18h of fasting significantly reduced immobility time in the forced swimming test (FST) without alteration in locomotor activity in the open field test. 9h fasting also enhanced the ratio of p-CREB/CREB in the frontal cortex and hippocampus. Co-administration of 9h of fasting and imipramine (30mg/kg, i.p) produced the additive antidepressant-like effects in the FST and increased the ratio of p-CREB/CREB. Meanwhile, the additive effects were partially reversed by treatment with a 5-HT2A/2C receptor agonist, (±)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) (5mg/kg, s.c). Furthermore, the antidepressant-like effects of 9h fasting was also blocked by DOI compared to the non-fasting control group. Serum corticosterone level, but not 5-HT and noradrenaline, was significantly increased in a time-dependent manner following different time periods of fasting. Taken together, these results suggest that acute fasting produces antidepressant-like effects via enhancement of the p-CREB/CREB ratio, and additive antidepressant-like effects of fasting with imipramine may be related to modulating 5-HT2 receptors. PMID:24036107

  7. 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests.

    PubMed

    Xu, Changjiang; Teng, Jijun; Chen, Weidong; Ge, Qiang; Yang, Zhiqi; Yu, Chunying; Yang, Zirong; Jia, William

    2010-12-01

    Ginseng has been used for mood adjustment in traditional Chinese medicine for thousands of years. Our previous study has shown that, total ginsenosides, the major pharmacologically functional ingredients of ginseng, possess antidepressant activity. In the present study, we hypothesized that an intestinal metabolite of ginseng, 20(S)-protopanaxadiol (code name S111), as a post metabolism compound (PMC) of ingested ginsenosides, may be responsible for the antidepressant activity of ginseng. To test this hypothesis, antidepressant-like activity of orally given S111 was measured in animal tests including tail suspension test, forced swimming test and rat olfactory bulbectomy depression model. In all those tests, S111 demonstrated antidepressant-like activity as potent as fluoxetine. S111 treated bulbectomy animals had higher levels of monoamine neurotransmitters in the brain and in vitro reuptake assay showed that S111 had a mild inhibitory effect. Furthermore, S111 but not fluoxetine significantly reduced brain oxidative stress and down-regulated serum corticosterone concentration in bulbectomy animals. No disturbance to central nervous system (CNS) normal functions were found in S111 treated animals. These results suggest that the ginseng active metabolite S111 is a potential antidepressant. Since the monoamine reuptake activity of this compound is rather weak, it remains to be investigated whether its antidepressant-like effect is by mechanisms that are different from current antidepressants. Furthermore, this study has demonstrated that post metabolism compounds (PMCs) of herb medicines such as S111 may be a novel source for drug discovery from medicinal herbs. PMID:20647027

  8. Antidepressant activity of fingolimod in mice

    PubMed Central

    di Nuzzo, Luigi; Orlando, Rosamaria; Tognoli, Cristina; Di Pietro, Paola; Bertini, Giuseppe; Miele, Jessica; Bucci, Domenico; Motolese, Marta; Scaccianoce, Sergio; Caruso, Alessandra; Mauro, Gianluca; De Lucia, Carmine; Battaglia, Giuseppe; Bruno, Valeria; Fabene, Paolo Francesco; Nicoletti, Ferdinando

    2015-01-01

    Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed with face and pharmacological validity. Chronic treatment with fingolimod (3 mg kg−1, i.p., once a day for 4 weeks) reduced the immobility time in the forced swim test (FST) in a large proportion of CUS mice. This treatment also caused anxiogenic-like effects in the social interaction test without affecting anxiety-like behavior in the elevated plus maze or spatial learning in the water maze. CUS mice showed reduced BDNF levels and enhanced HDAC2 levels in the hippocampus. These changes were reversed by fingolimod exclusively in mice that showed a behavioral response to the drug in the FST. Fingolimod treatment also enhanced H3 histone K14-acetylation and adult neurogenesis in the hippocampus of CUS mice. Fingolimod did not affect most of the parameters we have tested in unstressed control mice. The antidepressant-like activity of fingolimod was confirmed in mice chronically treated with corticosterone. These findings show for the first time that fingolimod exerts antidepressant-like effect acting in a “disease-dependent” manner, and raise the interesting possibility that the drug could relieve depressive symptoms in MS patients independently of its disease-modifying effect on MS. PMID:26171219

  9. Genetic Predictors of Response to Serotonergic and Noradrenergic Antidepressants in Major Depressive Disorder: A Genome-Wide Analysis of Individual-Level Data and a Meta-Analysis

    PubMed Central

    Tansey, Katherine E.; Guipponi, Michel; Perroud, Nader; Bondolfi, Guido; Domenici, Enrico; Evans, David; Hall, Stephanie K.; Hauser, Joanna; Henigsberg, Neven; Hu, Xiaolan; Jerman, Borut; Maier, Wolfgang; Mors, Ole; O'Donovan, Michael; Peters, Tim J.; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Aitchison, Katherine J.; Craig, Ian; Farmer, Anne; Wendland, Jens R.; Malafosse, Alain; Holmans, Peter; Lewis, Glyn; Lewis, Cathryn M.; Stensbøl, Tine Bryan; Kapur, Shitij; McGuffin, Peter; Uher, Rudolf

    2012-01-01

    Background It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. Methods and Findings The NEWMEDS consortium, an academia–industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10−8). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10−8) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D. Conclusions No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see

  10. Do SSRI Antidepressants Increase The Risk of Extrapyramidal Side Effects In Patients Taking Antipsychotics?

    PubMed Central

    Allsbrook, Matthew; Fries, Brant E.; Szafara, Kristina L.; Regal, Randolph E.

    2016-01-01

    Purpose: Among antidepressants, selective serotonin reup-take inhibitors (SSRIs) have enjoyed great popularity among clinicians as well as generally wide acceptance and tolerance among patients. A potentially overlooked side effect of SSRIs is the occasional occurrence of extrapyramidal symptoms (EPS), which could be a concern when SSRIs are used with antipsychotics. This study was designed to explore the possible association between SSRI antidepressant use and the incidence of EPS side effects in patients who take concomitant antipsychotic medications. Methods: The University of Michigan conducted a study at the four Michigan state mental health hospitals between May 2010 and October 2010. The Michigan Public Health Institute collected data using the InterRAI Mental Health Assessment (InterRAI MH). The present study is a retrospective cohort analysis of the cross-sectional data that were collected. Within these institutions, 693 residents were using antipsychotics. We measured the observed frequency of seven EPS recorded in the InterRAI MH within three groups of patients: 1) those on antipsychotic drugs who were taking an SSRI antidepressant; 2) those on antipsychotic drugs who were not taking an antidepressant; and 3) those on antipsychotic drugs who were taking a non-SSRI antidepressant. Differences in the prevalence of EPS were tested using one-way analysis of variance. Results: There were no significant differences in the observed EPS frequencies among the three groups (F2,18 = 0.01; P < 0.9901). Conclusion: In this study, SSRIs did not appear to potentiate the occurrence of EPS in patients using antipsychotics. PMID:26909002

  11. Antidepressant therapy: benefits and risks in perspective.

    PubMed

    Burrows, G D; Norman, T R; Dennerstein, L; Davies, B M

    1985-01-01

    The introduction of second generation antidepressants, such as mianserin and nomifensine, was prompted by the desire to produce drugs which were safer, had fewer side-effects and were faster acting than the tricyclics. A brief review of the data on mianserin and nomifensine is presented in relation to these aims. Some advantages for the new drugs can be claimed and the risks of severe adverse effects relating to blood dyscrasias in the case of mianserin, and fever in the case of nomifensine, appear outweighed by the therapeutic gains. PMID:3901673

  12. Faster, better, stronger: towards new antidepressant therapeutic strategies.

    PubMed

    O'Leary, Olivia F; Dinan, Timothy G; Cryan, John F

    2015-04-15

    Major depression is a highly prevalent disorder and is predicted to be the second leading cause of disease burden by 2020. Although many antidepressant drugs are currently available, they are far from optimal. Approximately 50% of patients do not respond to initial first line antidepressant treatment, while approximately one third fail to achieve remission following several pharmacological interventions. Furthermore, several weeks or months of treatment are often required before clinical improvement, if any, is reported. Moreover, most of the commonly used antidepressants have been primarily designed to increase synaptic availability of serotonin and/or noradrenaline and although they are of therapeutic benefit to many patients, it is clear that other therapeutic targets are required if we are going to improve the response and remission rates. It is clear that more effective, rapid-acting antidepressants with novel mechanisms of action are required. The purpose of this review is to outline the current strategies that are being taken in both preclinical and clinical settings for identifying superior antidepressant drugs. The realisation that ketamine has rapid antidepressant-like effects in treatment resistant patients has reenergised the field. Further, developing an understanding of the mechanisms underlying the rapid antidepressant effects in treatment-resistant patients by drugs such as ketamine may uncover novel therapeutic targets that can be exploited to meet the Olympian challenge of developing faster, better and stronger antidepressant drugs. PMID:25092200

  13. Challenges of withdrawal from chronic antidepressant medication: a healing odyssey.

    PubMed

    Whedon, James M; Rugo, Nancy A; Lux, Kenneth

    2013-01-01

    We report the case of a woman with posttraumatic stress disorder secondary to childhood sexual assault who attempted withdrawal from long-term use of antidepressant medication and experimented with a plethora of different therapies. The complex case history illustrates the potential difficulty of withdrawal from chronic antidepressant medication and the role of integrative therapies for posttraumatic stress disorder. PMID:23452714

  14. Quantifying esophagogastric junction contractility with a novel HRM topographic metric, the EGJ-Contractile Integral: normative values and preliminary evaluation in PPI non-responders

    PubMed Central

    Nicodème, Frédéric; Pipa-Muniz, Maria; Khanna, Kern; Kahrilas, Peter J.; Pandolfino, John E.

    2015-01-01

    Background Despite its obvious pathophysiological relevance, the clinical utility of measures of esophagogastric junction (EGJ) contractility is unsubstantiated. High-resolution manometry (HRM) may improve upon this with its inherent ability to integrate the magnitude of contractility over time and length of the EGJ. This study aimed to develop a novel HRM metric summarizing EGJ contractility and test its ability distinguish among subgroups of proton pump inhibitor non-responders (PPI-NRs). Methods 75 normal controls and 88 PPI-NRs were studied. All underwent HRM. PPI-NRs underwent pH-impedance monitoring on PPI therapy scored in terms of acid exposure, number of reflux events, and reflux-symptom correlation and grouped as meeting All Criteria, Some Criteria, or No Criteria of abnormality. Control HRM studies were used to establish normal values for candidate EGJ contractility metrics, which were then compared in their ability to differentiate among PPI-NR subgroups. Results The EGJ contractile integral (EGJ-CI), a metric integrating contractility across the EGJ for three respiratory cycles, best distinguished the All Criteria PPI-NR subgroup from controls and other PPI-NR subgroups. Normal values (median, [IQR]) for this measure were 39 mmHg-cm [25–55 mmHg-cm]. The correlation between the EGJ-CI and a previously proposed metric, the lower esophageal sphincter-pressure integral, that used a fixed 10s time frame and an atmospheric as opposed to gastric pressure reference was weak. Conclusion Among HRM metrics tested, the EGJ-CI was best in distinguishing PPI-NRs meeting All Criteria of abnormality on pH-impedance testing. Future prospective studies are required to explore its utility in management of broader groups of GERD patients. PMID:24460814

  15. Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

    PubMed Central

    Maciag, Dorota; Simpson, Kimberly L; Coppinger, David; Lu, Yuefeng; Wang, Yue; Lin, Rick CS; Paul, Ian A

    2011-01-01

    A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8–21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences. PMID:16012532

  16. Antidepressant-like Effect of Insulin in Streptozotocin-induced Type 2 Diabetes Mellitus Rats.

    PubMed

    Sestile, Caio C; Maraschin, Jhonatan C; Rangel, Marcel P; Cuman, Roberto K N; Audi, Elisabeth A

    2016-09-01

    This study evaluated the antidepressant-like effect of insulin compared to sertraline and a combination of insulin and sertraline in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats submitted to the forced swim test (FST). Male Wistar rats were daily treated for 21 days with insulin (1 or 2 IU/kg, i.p.), with the selective serotonin reuptake inhibitor (SSRI), sertraline (10 mg/kg, i.p.), or with a combination of insulin (1 or 2 IU/kg, i.p.) and sertraline (10 mg/kg, i.p.) and submitted to the FST. We also evaluated the water and food intake, urine volume and weight gain of the rats. Rats treated with STZ showed impaired glucose tolerance. Chronic treatment with sertraline showed an antidepressant-like effect in non-diabetic and diabetic rats. Furthermore, sertraline promoted lower weight gain in diabetic rats. Insulin reduced the immobility behaviour in T2DM rats with impaired glucose tolerance. In conclusion, our results showed that insulin has an antidepressant-like effect comparable to that of sertraline. Sertraline is effective as an antidepressant and reduces weight gain, which reinforces its superiority over other SSRIs in the treatment of major depression disorder in patients with T2DM. PMID:26857652

  17. EXERCISE IMPROVES SEXUAL FUNCTION IN WOMEN TAKING ANTIDEPRESSANTS: RESULTS FROM A RANDOMIZED CROSSOVER TRIAL

    PubMed Central

    Lorenz, Tierney Ahrold; Meston, Cindy May

    2014-01-01

    Background In laboratory studies, exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [1]. We evaluated if exercise improves sexual desire, orgasm, and global sexual functioning in women experiencing antidepressant-induced sexual side effects. Methods Fifty-two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only. They were randomized to complete either three weeks of exercise immediately before sexual activity (3×/week) or 3 weeks of exercise separate from sexual activity (3×/week). At the end of the first exercise arm, participants crossed to the other. We measured sexual functioning, sexual satisfaction, depression, and physical health. Results Exercise immediately prior to sexual activity significantly improved sexual desire and, for women with sexual dysfunction at baseline, global sexual function. Scheduling regular sexual activity significantly improved orgasm function; exercise did not increase this benefit. Neither regular sexual activity nor exercise significantly changed sexual satisfaction. Conclusions Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants. PMID:24754044

  18. N,N-dimethylglycine differentially modulates psychotomimetic and antidepressant-like effects of ketamine in mice.

    PubMed

    Lin, Jen-Cheng; Chan, Ming-Huan; Lee, Mei-Yi; Chen, Yi-Chyan; Chen, Hwei-Hsien

    2016-11-01

    Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine. The present study determined the effects of DMG on the ketamine-induced psychotomimetic, anesthetic and antidepressant-like effects in mice. DMG pretreatment reversed the ketamine-induced locomotor hyperactivity and impairment in the rotarod performance, novel location and novel object recognition tests, and prepulse inhibition. In addition, DMG alone exhibited antidepressant-like effects in the forced swim test and produced additive effects when combined with ketamine. However, DMG did not affect ketamine-induced anesthesia. These results reveal that DMG could antagonize ketamine's psychotomimetic effects, yet produce additive antidepressant-like effects with ketamine, suggesting that DMG might have antipsychotic potential and be suitable as an add-on therapy to ketamine for patients with treatment-resistant depression. PMID:27296677

  19. Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents.

    PubMed

    Sashidhara, Koneni V; Rao, K Bhaskara; Singh, Seema; Modukuri, Ram K; Aruna Teja, G; Chandasana, Hardik; Shukla, Shubha; Bhatta, Rabi S

    2014-10-15

    A series of amine substituted 3-phenyl coumarin derivatives were designed and synthesized as potential antidepressant agents. In preliminary screening, all compounds were evaluated in forced swimming test (FST), a model to screen antidepressant activity in rodents. Among the series, compounds 5c and 6a potentially decreased the immobility time by 73.4% and 79.7% at a low dose of 0.5 mg/kg as compared to standard drug fluoxetine (FXT) which reduced the immobility time by 74% at a dose of 20 mg/kg, ip. Additionally, these active compounds also exhibited significant efficacy in tail suspension test (TST) (another model to screen antidepressant compounds). Interestingly, rotarod and locomotor activity tests confirmed that these two compounds do not have any motor impairment effect and neurotoxicity in mice. Our studies demonstrate that the new 3-phenylcoumarin derivatives may serve as a promising antidepressant lead and hence pave the way for further investigation around this chemical space. PMID:25239852

  20. Comparison of antidepressant-like and abuse-related effects of phencyclidine in rats

    PubMed Central

    Hillhouse, Todd M.; Porter, Joseph H.; Negus, S. Stevens

    2014-01-01

    NMDA receptor antagonists such as ketamine have emerged as novel candidate treatments for major depressive disorder, but abuse potential of these agents is a concern. The NMDA antagonist phencyclidine has known abuse liability but undefined efficacy as an antidepressant. To further evaluate the relationship between antidepressant-like and abuse-related effects of NMDA antagonists, this study evaluated the effects of phencyclidine (1.0-10.0 mg/kg) in male Sprague-Dawley rats responding under two procedures that have been used to assess antidepressant-like effects [differential-reinforcement-of-low-rate (DRL) 72 s schedule of food reinforcement; N=9] and abuse-related drug effects [intracranial self-stimulation (ICSS); N=6]. Under the DRL 72 s schedule, phencyclidine (10.0 mg/kg) increased reinforcers and decreased responses without shifting the peak location of the interresponse time (IRT) distribution. Ketamine (10.0 mg/kg) also increased reinforcers and decreased responses, but unlike phencyclidine, it produced a rightward shift in the peak location of the IRT distribution. The 10.0 mg/kg phencyclidine dose that decreased DRL 72 s responding also decreased rates of ICSS for 50 min after its administration; however, abuse-related ICSS facilitation was observed at later times (100-300 min) or after a lower phencyclidine dose (3.2 mg/kg). These results suggest that phencyclidine produces weaker antidepressant-like effects, but stronger abuse-related effects than ketamine in these procedures. PMID:25315690

  1. Adaptation of a Motivational Interviewing Intervention to Improve Antidepressant Adherence among Latinos

    PubMed Central

    Interian, Alejandro; Martinez, Igda; Rios, Lisbeth Iglesias; Krejci, Jonathan; Guarnaccia, Peter J.

    2009-01-01

    Poor antidepressant adherence is a significant issue in depression treatment that adversely affects treatment outcomes. While being a common problem, it tends to be more common among Latinos. To address this problem, the current study adapted a Motivational Interviewing (MI) intervention to improve adherence among Latinos with depression. The adaptation process included six focus groups that elicited participants’ perspectives (N = 30), applying the intervention with test cases (N = 7) to fine tune the intervention, and eliciting feedback on the intervention (N = 5). The findings generated from these adaptation phases are described, along with a case example. Examples of adaptations to the MI included reframing antidepressant adherence as a way to luchar (struggle) against problems, focusing on motivation for improving depression and not just medication, refining methods for imparting antidepressant information, and inclusion of personalized visual feedback on dose-taking. The findings provide a description of the antidepressant issues experienced by a group of Latinos, as well as considerations for applying MI with this population. The intervention remained grounded in MI principles, but was contextualized for this Latino group. PMID:20438160

  2. Strategies to enhance the therapeutic efficacy of antidepressants: targeting residual symptoms

    PubMed Central

    Kurian, Benji T; Greer, Tracy L; Trivedi, Madhukar H

    2009-01-01

    Major depressive disorder (MDD) is an illness of great morbidity that affects many people across the world. The current goal for treatment of MDD is to achieve remission (i.e., no depressive symptoms). However, despite scientific advances in the treatment for MDD, antidepressants as first-line agents yield only modest remission rates. In fact, a recent study indicated that only one out of three subjects who received a standard, first-line antidepressant attained remission. Not achieving remission from depressive symptoms increases the risk of a more chronic and debilitating course of illness with frequent recurrences. Although a number of reasons contribute to these modest outcomes, the presence of residual symptoms is a major problem. Residual symptoms are defined as symptoms that linger despite an adequate dose and duration of an antidepressant medication. This article reviews the prevalence and clinical impact of common residual symptoms and discusses the utility of aggressively addressing residual symptoms to enhance the efficacy of antidepressant medications. PMID:19589048

  3. [The effects of antidepressants on sleep in depressed patients with particular reference to trazodone in comparison to agomelatine, amitriptyline, doxepin, mianserine and mirtazapine].

    PubMed

    Wichniak, Adam; Wierzbicka, Aleksandra

    2011-07-01

    Disturbed sleep is a core symptom of depression and is among diagnostic criteria for depressive episode. Effects of an antidepressant drug on sleep are important for its clinical profile. Rapid improvement of sleep quality is particularly indicated in depressed patients with insomnia, anxiety, agitation and suicidal thoughts. The aim of the study was to evaluate the effects of trazodone on sleep in depressed patients in comparison to other sleep promoting antidepressants: agomelatine, amitriptyline, doxepin, mianserine and mirtazapine according to analysis of scientific publications. Sedative antidepressants including trazodone are regarded as treatment of choice in depression with agitation, anxiety or insomnia. They are also frequently used in low dose to promote sleep, as an alternative to hypnotics. Such approach to treatment of insomnia in depressed patients protects them against dependence on hypnotic drugs. Additionally, the antagonistic action of antidepressants on serotonergic 5-HT2 receptors improves not only the sleep continuity, but promotes also slow wave sleep. Trazodone and mirtazapine in comparison to many other antidepressants do not suppress REM sleep. Antidepressants have different effects on sleep. In treatment of depression sedative antidepressants should be administered in the full, recommended dose. However, if they are administered as concomitant treatment only to promote sleep, low doses are indicated. Too late administration time and too high dose are the most common factors related to failure of insomnia treatment with these drugs. PMID:21870714

  4. The Prefrontal Dectin-1/AMPA Receptor Signaling Pathway Mediates The Robust and Prolonged Antidepressant Effect of Proteo-β-Glucan from Maitake.

    PubMed

    Bao, Hongkun; Ran, Pengzhan; Zhu, Ming; Sun, Lijuan; Li, Bai; Hou, Yangyang; Nie, Jun; Shan, Liping; Li, Hongliang; Zheng, Shangyong; Xu, Xiufeng; Xiao, Chunjie; Du, Jing

    2016-01-01

    Proteo-β-glucan from Maitake (PGM) is a strong immune regulator, and its receptor is called Dectin-1. Cumulative evidence suggests that AMPA receptors are important for the treatment of depression. Here, we report that PGM treatment leads to a significant antidepressant effect in the tail suspension test and forced swim test after sixty minutes of treatment in mice. After five consecutive days of PGM treatment, this antidepressant effect remained. PGM treatment did not show a hyperactive effect in the open field test. PGM significantly enhanced the expression of its receptor Dectin-1, as well as p-GluA1(S845) and GluA1, but not GluA2 or GluA3 in the prefrontal cortex (PFC) after five days of treatment. The Dectin-1 inhibitor Laminarin was able to block the antidepressant effect of PGM. At the synapses of PFC, PGM treatment significantly up-regulated the p-GluA1(S845), GluA1, GluA2, and GluA3 levels. Moreover, PGM's antidepressant effects and the increase of p-GluA1(S845)/GluA1 lasted for 3 days after stopping treatment. The AMPA-specific antagonist GYKI 52466 was able to block the antidepressant effect of PGM. This study identified PGM as a novel antidepressant with clinical potential and a new antidepressant mechanism for regulating prefrontal Dectin-1/AMPA receptor signalling. PMID:27329257

  5. The Prefrontal Dectin-1/AMPA Receptor Signaling Pathway Mediates The Robust and Prolonged Antidepressant Effect of Proteo-β-Glucan from Maitake

    PubMed Central

    Bao, Hongkun; Ran, Pengzhan; Zhu, Ming; Sun, Lijuan; Li, Bai; Hou, Yangyang; Nie, Jun; Shan, Liping; Li, Hongliang; Zheng, Shangyong; Xu, Xiufeng; Xiao, Chunjie; Du, Jing

    2016-01-01

    Proteo-β-glucan from Maitake (PGM) is a strong immune regulator, and its receptor is called Dectin-1. Cumulative evidence suggests that AMPA receptors are important for the treatment of depression. Here, we report that PGM treatment leads to a significant antidepressant effect in the tail suspension test and forced swim test after sixty minutes of treatment in mice. After five consecutive days of PGM treatment, this antidepressant effect remained. PGM treatment did not show a hyperactive effect in the open field test. PGM significantly enhanced the expression of its receptor Dectin-1, as well as p-GluA1(S845) and GluA1, but not GluA2 or GluA3 in the prefrontal cortex (PFC) after five days of treatment. The Dectin-1 inhibitor Laminarin was able to block the antidepressant effect of PGM. At the synapses of PFC, PGM treatment significantly up-regulated the p-GluA1(S845), GluA1, GluA2, and GluA3 levels. Moreover, PGM’s antidepressant effects and the increase of p-GluA1(S845)/GluA1 lasted for 3 days after stopping treatment. The AMPA-specific antagonist GYKI 52466 was able to block the antidepressant effect of PGM. This study identified PGM as a novel antidepressant with clinical potential and a new antidepressant mechanism for regulating prefrontal Dectin-1/AMPA receptor signalling. PMID:27329257

  6. Facebook Enhances Antidepressant Pharmacotherapy Effects

    PubMed Central

    Mota Pereira, Jorge

    2014-01-01

    Treatment-resistant major depressive disorder (TR-MDD) is a complex condition, with very low remission rates. In recent years some studies have been conducted on the implementation of cognitive behavioral therapy and psychodynamic psychotherapy interventions via the Internet to MDD patients, and results have been promising. However, there have been no studies in patients with TR-MDD nor with the use of Facebook with the psychiatrist as “friend.” 60 TR-MDD patients were randomized to one of three groups: Facebook group with psychiatrist as “friend,” Facebook group without psychiatrist as “friend,” and control group (no Facebook use). Both Facebook groups spent at least 1 hour/day on Facebook, 7 days/week, during the 3 months. All patients maintained their usual pharmacotherapy. All participants were evaluated at baseline and at 1, 2, and 3 months for depressive symptoms using HAD17 and BDI-II. Results show that both Facebook groups had a decrease on HADM17 and BDI-II scores as well as higher remission and response rates than the control group, with better results if the psychiatrist was a “friend” on Facebook. Therefore, in TR-MDD, Facebook can be used as an effective enhancement therapy, adjuvant to pharmacological therapy with regular consultations, especially if the psychiatrist is the patient's online “friend.” PMID:24574930

  7. Facebook enhances antidepressant pharmacotherapy effects.

    PubMed

    Mota Pereira, Jorge

    2014-01-01

    Treatment-resistant major depressive disorder (TR-MDD) is a complex condition, with very low remission rates. In recent years some studies have been conducted on the implementation of cognitive behavioral therapy and psychodynamic psychotherapy interventions via the Internet to MDD patients, and results have been promising. However, there have been no studies in patients with TR-MDD nor with the use of Facebook with the psychiatrist as "friend." 60 TR-MDD patients were randomized to one of three groups: Facebook group with psychiatrist as "friend," Facebook group without psychiatrist as "friend," and control group (no Facebook use). Both Facebook groups spent at least 1 hour/day on Facebook, 7 days/week, during the 3 months. All patients maintained their usual pharmacotherapy. All participants were evaluated at baseline and at 1, 2, and 3 months for depressive symptoms using HAD17 and BDI-II. Results show that both Facebook groups had a decrease on HADM17 and BDI-II scores as well as higher remission and response rates than the control group, with better results if the psychiatrist was a "friend" on Facebook. Therefore, in TR-MDD, Facebook can be used as an effective enhancement therapy, adjuvant to pharmacological therapy with regular consultations, especially if the psychiatrist is the patient's online "friend." PMID:24574930

  8. κ-opioid receptors are not necessary for the antidepressant treatment of neuropathic pain

    PubMed Central

    Megat, Salim; Bohren, Yohann; Doridot, Stephane; Gaveriaux-Ruff, Claire; Kieffer, Brigitte L; Freund-Mercier, Marie-José; Yalcin, Ipek; Barrot, Michel

    2015-01-01

    Background and Purpose Tricyclic antidepressants are used clinically as first-line treatments for neuropathic pain. Opioid receptors participate in this pain-relieving action, and preclinical studies in receptor-deficient mice have highlighted a critical role for δ-, but not μ-opioid receptors. In this study, we investigated whether κ-opioid (KOP) receptors have a role in the antiallodynic action of tricyclic antidepressants. Experimental Approach We used a model of neuropathic pain induced by unilateral sciatic nerve cuffing. In this model, the mechanical allodynia was evaluated using von Frey filaments. Experiments were conducted in C57BL/6J mice, and in KOP receptor-deficient mice and their wild-type littermates. The tricyclic antidepressant nortriptyline (5 mg·kg−1) was delivered twice a day for over 2 weeks. Agonists and antagonists of opioid receptors were used to test the selectivity of the KOP receptor antagonist norbinaltorphimine (nor-BNI) in mice with neuropathic pain. Key Results After 12 days of treatment, nortriptyline relieved neuropathic allodynia in both wild-type and KOP receptor-deficient mice. Surprisingly, acute nor-BNI reversed the effect of nortriptyline in both wild-type and KOP receptor-deficient mice. Further experiments showed that nor-BNI action was selective for KOP receptors at a late time-point after its administration (8 h), but not at an early time-point, when it may also interact with δ-opioid (DOP) receptors. Conclusions and Implications KOP receptors are not necessary for the effect of a tricyclic antidepressant against neuropathic allodynia. These findings together with previous data indicate that the DOP receptor is the only opioid receptor that is necessary for the antiallodynic action of antidepressants. PMID:25297905

  9. Behavioral and Biochemical Evidences for Antidepressant-Like Activity of Celastrus Paniculatus Seed Oil in Mice

    PubMed Central

    Valecha, Rekha; Dhingra, Dinesh

    2016-01-01

    Introduction: Celastrus paniculatus seed oil, commonly known as Malkangni or Jyotishmati, was in use from time immemorial to treat brain related disorders. Celastrus paniculatus seed oil has significant antidepressant-like activity in chronic unpredictable stressed mice. The present study was undertaken to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil in unstressed mice and to explore its mechanism of action. Methods: The seed oil (50, 100, and 200 mg/kg, PO) and fluoxetine per se were administered for 14 successive days to Swiss young albino mice. On the 14th day, 60 min after drug administration, animals were subjected to Tail Suspension Test (TST) and Forced Swim Test (FST). The mechanism of action was also studied. Results: The oil significantly decreased immobility period of mice in both tail suspension test and forced swim test, indicating its significant antidepressant-like activity. The efficacy was found to be comparable to fluoxetine (P<0.0001). ED50 value of celastrus seed oil using FST and TST were 17.38 and 31.62 mg/kg, respectively. The oil did not show any significant effect on locomotor activity. It significantly inhibited brain MAO–A activity and decreased plasma corticosterone levels. Sulpiride (selective D2-receptor antagonist), p-CPA (tryptophan hydroxylase inhibitor), and baclofen (GABAB agonist) significantly attenuated the oil-induced antidepressant-like effect, when assessed during TST. Discussion: Celastrus paniculatus seed oil produced significant antidepressant-like effect in mice possibly through interaction with dopamine D2, serotonergic, and GABAB receptors; as well as inhibition of MAO–A activity and decrease in plasma corticosterone levels. PMID:27303599

  10. Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

    PubMed

    Graf, Heiko; Metzger, Coraline D; Walter, Martin; Abler, Birgit

    2016-01-01

    Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy. PMID:26555033

  11. Update and Critique of Natural Remedies as Antidepressant Treatments

    PubMed Central

    Mischoulon, David

    2009-01-01

    SYNOPSIS The popularity of natural or “alternative” remedies to treat medical and psychiatric disorders has accelerated dramatically over the past decade, in the United States and worldwide. This article reviews the evidence for clinical efficacy, active ingredients, mechanisms of action, recommended dosages, and toxicities of the three best-studied putative natural antidepressants, St. John's Wort (hypericum), S-adenosyl methionine, and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Despite growing evidence for efficacy and safety, more comprehensive studies are required before these remedies can be recommended as safe and effective alternatives or adjuncts to conventional psychotropic agents. There are limited data regarding safety in pregnancy and during lactation, and caution is therefore recommended in women who are pregnant or breastfeeding. PMID:19944301

  12. Antidepressants and their effect on cognition in major depressive disorder.

    PubMed

    Papakostas, George I

    2015-08-01

    Cognitive functioning is a symptom of major depressive disorder (MDD) that deserves particular attention by clinicians and researchers. Despite the fact that cognitive dysfunction represents a symptom of MDD as well as a functional outcome measure, cognition has been insufficiently investigated in antidepressant trials. While, until recently, few placebo-controlled trials have measured cognition in MDD, those examples which did have consisted of older adults. Of agents tested thus far in placebo-controlled trials (citalopram, duloxetine, vortioxetine), only the latter has been studied in patients aged 18-65, and only the latter has been shown to be superior to placebo in improving measures of executive functioning and to do so across adult age groups. Both duloxetine and vortioxetine appear to result in greater improvements than placebo in immediate and delayed memory. Clinicians who wish to improve the psychosocial recovery of patients with MDD should be familiar with studies of new options for treatment. PMID:26335095

  13. Association of Changes in Norepinephrine and Serotonin Transporter Expression with the Long-Term Behavioral Effects of Antidepressant Drugs

    PubMed Central

    Zhao, Zaorui; Zhang, Han-Ting; Bootzin, Elianna; Millan, Mark J; O’Donnell, James M

    2009-01-01

    Previous work has shown that repeated desipramine treatment causes downregulation of the norepinephrine transporter (NET) and persistent antidepressant-like effects on behavior, ie effects observed 2 days after discontinuation of drug treatment when acute effects are minimized. The present study examined whether this mechanism generalizes to other antidepressants and also is evident for the serotonin transporter (SERT). Treatment of rats for 14 days with 20 mg/kg per day protriptyline or 7.5 mg/kg per day sertraline reduced NET and SERT expression, respectively, in cerebral cortex and hippocampus; these treatments also induced a persistent antidepressant-like effect on forced-swim behavior. Increased serotonergic neurotransmission likely mediated the behavioral effect of sertraline, as it was blocked by inhibition of serotonin synthesis with p-chlorophenylalanine; a parallel effect was observed previously for desipramine and noradrenergic neurotransmission. Treatment with 20 mg/kg per day reboxetine for 42, but not 14, days reduced NET expression; antidepressant-like effects on behavior were observed for both treatment durations. Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced antidepressant-like effects on behavior without altering NET or SERT expression. For all drugs tested, reductions of NET and SERT protein were not accompanied by reduced NET or SERT mRNA in locus coeruleus or dorsal raphe nucleus, respectively. Overall, the present results suggest an important, though not universal, role for NET and SERT regulation in the long-term behavioral effects of antidepressants. Understanding the mechanisms underlying transporter regulation in vivo may suggest novel targets for the development of antidepressant drugs. PMID:18923402

  14. Comparative efficacy and tolerability of first-generation and newer-generation antidepressant medications for depressive disorders in children and adolescents: study protocol for a systematic review and network meta-analysis

    PubMed Central

    Zhou, Xinyu; Qin, Bin; Whittington, Craig; Cohen, David; Liu, Yiyun; Del Giovane, Cinzia; Michael, Kurt D; Zhang, Yuqing; Xie, Peng

    2015-01-01

    Introduction Depressive disorders are among the most common psychiatric disorders in children and adolescents, and have adverse effects on their psychosocial functioning. Questions concerning the efficacy and safety of antidepressant medications in the treatment of depression in children and adolescents, led us to integrate the direct and indirect evidence using network meta-analysis to create hierarchies of these drugs. Methods and analysis Seven databases with PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL, LiLACS and PsycINFO will be searched from 1966 to December 2013 (updated to May, 2015). There are no restrictions on language or type of publication. Randomised clinical trials assessing first-generation and newer-generation antidepressant medications against active comparator or placebo as acute treatment for depressive disorders in children and adolescents (under 18 years of age) will be included. The primary outcome for efficacy will be mean improvement in depressive symptoms, as measured by the mean change score of a depression rating scale from baseline to post-treatment. The tolerability of treatment will be defined as side effect discontinuation, as defined by the proportion of patients who discontinued treatment due to adverse events during the trial. We will also assess the secondary outcome for efficacy (response rate), acceptability (all-cause discontinuation) and suicide-related outcomes. We will perform the Bayesian network meta-analyses for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. Dissemination The network meta-analysis will provide useful information on antidepressant treatment for child and adolescent depression. The results will be disseminated through peer-reviewed publication or conference presentations. Trial registration number PROSPERO CRD42015016023. PMID:26353868

  15. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    PubMed Central

    Amin, Bahareh; Nakhsaz, Alireza; Hosseinzadeh, Hossein

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration. PMID:26468466

  16. Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants.

    PubMed

    Ricken, Roland; Adli, Mazda; Lange, Claudia; Krusche, Esther; Stamm, Thomas J; Gaus, Sebastian; Koehler, Stephan; Nase, Sarah; Bschor, Tom; Richter, Christoph; Steinacher, Bruno; Heinz, Andreas; Rapp, Michael A; Borgwardt, Stefan; Hellweg, Rainer; Lang, Undine E

    2013-12-01

    In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms. PMID:24018547

  17. The antidepressant- and anxiolytic-like activities of new xanthone derivative with piperazine moiety in behavioral tests in mice

    PubMed Central

    Pytka, Karolina; Żmudzka, Elżbieta; Lustyk, Klaudia; Rapacz, Anna; Olczyk, Adrian; Gałuszka, Adam; Waszkielewicz, Anna; Marona, Henryk; Sapa, Jacek; Barbara, Filipek

    2016-01-01

    Objectives: Xanthones are flavonoids with numerous activities, including antioxidant, antidepressant., or anxiolytic-like. Therefore, the aim of our study was to determine antidepressant- and anxiolytic-like properties of four xanthone derivatives (3-chloro-5-[(4-methylpiperazin-1-yl)methyl]-9H-xanthen-9-one dihydrochloride [HBK-5], 6-methoxy-2-[(4-methylpiperazin-1-yl) methyl]-9H-xanthen-9-one dihydrochloride, 2-[(4-benzylpiperazin-1-yl) methyl]-6-methoxy-9H-xanthen-9-one dihydrochloride, 2-{[4-(2-methoxyphenyl) piperazin-1-yl] methyl}-9H-xanthen-9-one hydrochloride), as well as the influence on cognitive and motor function of active compounds, using animal models. Materials and Methods: To determine the antidepressant-like activity, we used forced swim test (FST) and tail suspension test (TST) in mice. We evaluated anxiolytic-like properties in the four-plate test in mice. We studied the influence on cognitive and motor function in passive avoidance step-through and chimney tests, respectively. Results: The antidepressant-like activity (in both FST and TST) showed only HBK-5. Moreover, the compound was also active in the four-plate test, which suggests that it possessed anxiolytic-like properties. HBK-5 did not cause any cognitive and motor deficits in mice at antidepressant- and anxiolytic-like doses. Conclusions: HBK-5 may have potential in the treatment of depression or anxiety disorders, but this issue needs further studies. PMID:27298499

  18. Neurogenomic Evidence for a Shared Mechanism of the Antidepressant Effects of Exercise and Chronic Fluoxetine in Mice

    PubMed Central

    Huang, Guo-Jen; Ben-David, Eyal; Tort Piella, Agnès; Edwards, Andrew; Flint, Jonathan; Shifman, Sagiv

    2012-01-01

    Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug – fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy. PMID:22558262

  19. Long-Term Weight Change after Initiating Second-Generation Antidepressants

    PubMed Central

    Arterburn, David; Sofer, Tamar; Boudreau, Denise M.; Bogart, Andy; Westbrook, Emily O.; Theis, Mary Kay; Simon, Greg; Haneuse, Sebastien

    2016-01-01

    (1) Objective: To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change; (2) Methods: We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment; (3) Results: In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: −11.3, −2.8; p-value < 0.01); smokers who initiated bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: −2.3, 6.8; p-value = 0.33). Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02); (4) Conclusion: Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications. PMID:27089374

  20. Antidepressants and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains.

    PubMed

    Eisensamer, Brigitte; Uhr, Manfred; Meyr, Sabrina; Gimpl, Gerald; Deiml, Tobias; Rammes, Gerhard; Lambert, Jeremy J; Zieglgänsberger, Walter; Holsboer, Florian; Rupprecht, Rainer

    2005-11-01

    Despite different chemical structure and pharmacodynamic signaling pathways, a variety of antidepressants and antipsychotics inhibit ion fluxes through 5-HT3 receptors in a noncompetitive manner with the exception of the known competitive antagonists mirtazapine and clozapine. To further investigate the mechanisms underlying the noncompetitive inhibition of the serotonin-evoked cation current, we quantified the concentrations of different types of antidepressants and antipsychotics in fractions of sucrose flotation gradients isolated from HEK293 (human embryonic kidney 293) cells stably transfected with the 5-HT3A receptor and of N1E-115 neuroblastoma cells in relation to the localization of the 5-HT3 receptor protein within the cell membrane. Western blots revealed a localization of the 5-HT3 receptor protein exclusively in the low buoyant density (LBD) fractions compatible with a localization within raft-like domains. Also, the antidepressants desipramine, fluoxetine, and reboxetine and the antipsychotics fluphenazine, haloperidol, and clozapine were markedly enriched in LBD fractions, whereas no accumulation occurs for mirtazapine, carbamazepine, moclobemide, and risperidone. The concentrations of psychopharmacological drugs within LBD fractions was strongly associated with their inhibitory potency against serotonin-induced cation currents. The noncompetitive antagonism of antidepressants at the 5-HT3 receptor was not conferred by an enhancement of receptor internalization as shown by immunofluorescence studies, assessment of receptor density in clathrin-coated vesicles, and electrophysiological recordings after coexpression of a dominant-negative mutant of dynamin I, which inhibits receptor internalization. In conclusion, enrichment of antidepressants and antipsychotics in raft-like domains within the cell membrane appears to be crucial for their antagonistic effects at ligand-gated ion channels such as 5-HT3 receptors. PMID:16267227

  1. Antidepressant-like effect of Tagetes lucida Cav. extract in rats: involvement of the serotonergic system.

    PubMed

    Gabriela, Guadarrama-Cruz; Javier, Alarcón-Aguilar Francisco; Elisa, Vega-Avila; Gonzalo, Vázquez-Palacios; Herlinda, Bonilla-Jaime

    2012-01-01

    It has been demonstrated that the decoction of the aerial parts of Tagetes lucida Cav. produces an antidepressant effect during the forced swimming test (FST) in rats. The aim of this study was to evaluate the effect of different organic extracts and one aqueous extract of the aerial parts of T. lucida on the FST. In addition, the possible involvement of the serotonergic system in the antidepressant-like effect of T. lucida in the FST was evaluated, as was its potential toxicological effect. The different extracts of T. lucida (methanol, hexane, dichloromethane and aqueous, 10 and 50 mg/kg), as well as fluoxetine (FLX, 5 mg/kg), were administered per os (p.o.) to rats for 14 days. All animals were subjected to the FST. Only the aqueous extract of T. lucida at a dose of 50 mg/kg significantly reduced immobility behavior and increased swimming in the FST, similar to FLX. Later, the aqueous extract of T. lucida (50mg/kg) was administered for 1, 7 and 14 days. An antidepressant effect was observed after 7 days of treatment. To evaluate the participation of the serotoninergic system, the animals were pretreated with PCPA, an inhibitor of serotonin synthesis (100 mg/kg/day for 4 consecutive days). The animals were treated with the aqueous extract of T. lucida (50 mg/kg) and FLX (5 mg/kg) 24 h after the final injection and were then subjected to the FST. Pretreatment with PCPA inhibited the antidepressant effect of both T. lucida and FLX. Finally, T. lucida was administered p.o. and intraperitoneal route to evaluate its acute toxicological effect. The aqueous extract of T. lucida, administered p.o., did not produce lethality or any significant changes in behavior. In conclusion, the aqueous extract of T. lucida manifested an antidepressant-like effect in the FST mediated by the serotonergic system, with no adverse effects when administered p.o. PMID:22809029

  2. Long-Term Weight Change after Initiating Second-Generation Antidepressants.

    PubMed

    Arterburn, David; Sofer, Tamar; Boudreau, Denise M; Bogart, Andy; Westbrook, Emily O; Theis, Mary Kay; Simon, Greg; Haneuse, Sebastien

    2016-01-01

    (1) OBJECTIVE: To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change; (2) METHODS: We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment; (3) RESULTS: In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: -11.3, -2.8; p-value < 0.01); smokers who initiated bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: -2.3, 6.8; p-value = 0.33). Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02); (4) CONCLUSION: Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications. PMID:27089374

  3. Short communication-Evaluation of antianxiety and antidepressant properties of Carthamus tinctorius L. (Safflower) petal extract.

    PubMed

    Qazi, Nasreen; Khan, Rafeeq Alam; Rizwani, Ghazala H

    2015-05-01

    Nowadays anxiety and depression are most commonly encountered diseases. They are not only difficult to diagnose but even difficult to treat since both are sometimes seen together or one predisposes the other. Apart from this side effect profile of these drugs is also high; hence there is immense scope for the herbal drugs to treat these disorders. Present study was therefore performed to evaluate the antianxiety and antidepressant effect of Carthamus tinctorius petal extract. 28 white albino rats bred in the animal house of Department of Pharmacology, University of Karachi weighing 180-220gm were randomly divided into four groups (n=7/group) to assess behavioral effects. The anxiolytic and antidepressant effects of Carthamus tinctorius petal extract were evaluated using elevated plus maize and forced swim test respectively at100 and 200mg/kg. These effects were compared with standard drugs Diazepam (anxiolytic) 2mg/kg and Nortriptyline (antidepressant) 12.5mg/kg. Results show that CT produced highly significant anxiolytic and anti-depressant effects at both doses as compared to control, similar to standard anxiolytic and antidepressant drugs diazepam and nortriptyline. It increased the latency of first entry to closed arms and the time spent in open arms very significantly at both doses while entries to open arm were increased significantly at 100mg/kg and very significantly at 200mg/kg in EPM test and increased the immobility time very significantly in FST. Hence it can be concluded that CT may be used as an alternative therapeutic agent while treating patients with anxiety and depressive disorders. PMID:26004733

  4. Antidepressant or Antipsychotic Overdose in the Intensive Care Unit - Identification of Patients at Risk.

    PubMed

    Borg, Linda; Julkunen, Anna; Rørbaek Madsen, Kristian; Strøm, Thomas; Toft, Palle

    2016-07-01

    It is often advised that patients who have ingested an overdose of antidepressants (AD) or antipsychotics (AP) are monitored with continuous ECG for minimum of 12-24 hr. These patients are often observed in an ICU. Our aim was to identify the number of patients with AD and/or AP overdose without adverse signs at hospital admission that turned out to need intensive care treatment. The effect of the antidepressants overdose risk assessment (ADORA) system was evaluated in patients with antidepressant as well as antipsychotic overdose. Our hypothesis was that patients with low ADORA do not need intensive care treatment. This retrospective study was conducted in adult patients admitted to the ICU at Odense University Hospital after an overdose with AP and/or AD between 1 January 2009 and 1 September 2014. Patients with predefined adverse signs in the emergency department were excluded due to obvious need of intensive care. Of the 157 patients included, 12 patients (8%) developed events during the ICU stay. Only 3 patients received intubation, vasoactive drugs and/or dialysis. None developed ventricular dysrhythmias. There were no fatalities. All the patients with low-risk assessment by ADORA within the first 6 hr did not develop events within the first 24 hr after hospital admission. The vast majority of patients with AD and/or AP overdose and no adverse signs at admission did not require intensive care treatment. Low-risk ADORA identified patients with antidepressant as well as antipsychotic overdose who would not require initial intensive care treatment. This is the first time the ADORA system has been evaluated in patients with antidepressant as well as antipsychotic overdose. PMID:26663682

  5. Antidepressant-like activity of turmerone in behavioral despair t