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Sample records for acute antidepressant treatment

  1. Contrasting effects of acute vs. chronic tricyclic antidepressant treatment on central morphine analgesia.

    PubMed

    Kellstein, D E; Malseed, R T; Goldstein, F J

    1984-12-01

    Antinociception following central opioid microinjection in rats was assessed weekly via a tail-flick procedure during chronic tricyclic antidepressant (TCA) treatment. (1) Daily TCA: Subcutaneous injections of desipramine (DMI), 30 mg/kg, chlorimipramine (CMI), 10 mg/kg, or saline, 1 ml/kg, were given daily for 22 days. Morphine sulfate (M), 5 micrograms, was microinjected into the ventrolateral periaqueductal gray (VLPAG) at 7 day intervals. On day 1, DMI or CMI enhanced M analgesia whereas saline did not. Augmentation of M disappeared by days 8 and 15 for CMI and DMI, respectively, and was replaced by attenuation which was still observed on day 22 for both TCAs. L-Tryptophan (LT), 100 mg/kg, i.p., on days 15 and 22 temporarily restored TCA enhancement of M. Fourteen days after cessation of all daily TCA treatments, enhancement of M by CMI was similar to that observed on day 1, whereas recovery of DMI-induced facilitation was incomplete. (2) Weekly TCA: Weekly treatment with DMI, CMI, or saline in the same doses as above had similar effects. M analgesia was enhanced by the TCAs but not saline on day 1; this facilitation was absent by day 15. Attenuation of M by DMI or CMI was evident on day 22; 2 weeks after cessation of all weekly TCA treatments, complete recovery of TCA-induced augmentation was observed. Loss of M facilitation during chronic daily or weekly TCA administration may be related to reduction of central opioid and/or 5-HT2 receptors. PMID:6097858

  2. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Szuster-Ciesielska, Agnieszka; Wyska, Elżbieta; Wlaź, Piotr

    2016-10-01

    Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required. PMID:27283174

  3. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.

    PubMed

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Szuster-Ciesielska, Agnieszka; Wyska, Elżbieta; Wlaź, Piotr

    2016-10-01

    Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required.

  4. [Acute intoxications by tricyclic antidepressants (author's transl)].

    PubMed

    Bourin, M; Ginies, G; Renard, J P; Lamisse, F; Choutet, P; Breteau, M

    The authors report 87 cases of acute voluntary intoxications with tricyclic antidepressants. They essentially studied the cardiac complications; and conclude that the prognosis is more severe than for other intoxications.

  5. Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Acute Treatment of Adults with Major Depression

    ERIC Educational Resources Information Center

    Dimidjian, Sona; Hollon, Steven D.; Dobson, Keith S.; Schmaling, Karen B.; Kohlenberg, Robert J.; Addis, Michael E.; Gallop, Robert; McGlinchey, Joseph B.; Markley, David K.; Gollan, Jackie K.; Atkins, David C.; Dunner, David L.; Jacobson, Neil S.

    2006-01-01

    Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have…

  6. Antidepressant treatment in anxiety disorders.

    PubMed

    Bespalov, Anton Y; van Gaalen, Marcel M; Gross, Gerhard

    2010-01-01

    Antidepressant drug treatment is the clinical standard of care for all types of anxiety disorders. Broad efficacy of selective serotonin reuptake inhibitors suggests the importance of enhanced serotonergic function of the anxiolytic properties of current antidepressants. However, analysis of the preclinical evidence indicates that most conventional "anxiolytic" drug tests are not sensitive to antidepressants. Such dissociation is not surprising because of the traditional approach to validation of preclinical tests that is to a large extent based on establishing face validity as well as sensitivity to benzodiazepine anxiolytics. The present review argues for extending the cognitive model of antidepressant drug action to cover their anxiolytic properties as well. Such an approach is based on ambiguity or uncertainty in a broad sense as the hallmark of human stress that has different expressions ready for experimental modeling. These possibilities include schedule-induced behaviors that are directly based on intermittent reinforcement, conditioning to ambiguous stimuli, social stress where agonistic confrontations are possible but not predictable or controlled by the subject, and an even larger class of behaviors that are critically dependent on the inhibition of the prepotent responses in exchange for the ambiguous possibility of a later gain in reinforcement. Interestingly, in all these cases, antidepressant drug treatment is clearly effective in preclinical laboratory settings. One of the cognitive functions that appears to be affected by antidepressant drugs is inhibitory control. Inhibition of prepotent responding has beneficial effects in the "uncertainty" stress situations discussed above and therefore it is this cognitive function that may be critical for anxiolytic effects of antidepressants and novel anxiolytic drug development. PMID:21309117

  7. Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice

    PubMed Central

    Yang, Li-Ping; Jiang, Fang-Jie; Wu, Gui-Sheng; Deng, Ke; Wen, Meng; Zhou, Xiaoju; Hong, Xuechuan; Zhu, Michael X.; Luo, Huai-Rong

    2015-01-01

    Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research. PMID:26317356

  8. 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

  9. Comparative efficacy and acceptability of first-generation and second-generation antidepressants in the acute treatment of major depression: protocol for a network meta-analysis

    PubMed Central

    Salanti, Georgia; Atkinson, Lauren Z; Leucht, Stefan; Ruhe, Henricus G; Turner, Erick H; Chaimani, Anna; Ogawa, Yusuke; Takeshima, Nozomi; Hayasaka, Yu; Imai, Hissei; Shinohara, Kiyomi; Suganuma, Aya; Watanabe, Norio; Stockton, Sarah; Geddes, John R

    2016-01-01

    Introduction Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network meta-analysis aimed at updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression. Methods and analysis We will include all randomised controlled trials reported as double-blind and comparing one active drug with another or with placebo in the acute phase treatment of major depression in adults. We are interested in comparing the following active agents: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The main outcomes will be the proportion of patients who responded to or dropped out of the allocated treatment. Published and unpublished studies will be sought through relevant database searches, trial registries and websites; all reference selection and data extraction will be conducted by at least two independent reviewers. We will conduct a random effects network meta-analysis to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. To rank the various treatments for each outcome, we will use the surface under the cumulative ranking curve and the mean ranks. We will employ local as well as global methods to evaluate consistency. We will fit our model in a Bayesian framework using OpenBUGS, and produce results and various checks in Stata and R. We will also assess the quality of evidence contributing to network

  10. Ketamine: stimulating antidepressant treatment?

    PubMed Central

    Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A.; Gitlin, Michael; Kennedy, Sidney H.; Ketter, Terence A.; Lam, Raymond W.; McShane, Rupert; Mitchell, Alex J.; Ostacher, Michael J.; Rizvi, Sakina J.; Thase, Michael E.; Tohen, Mauricio

    2016-01-01

    Speaker’s Bureau payments): GlaxoSmithKline, and Sunovion Pharmaceuticals; royalties from American Psychiatric Publishing, Inc. Also, AstraZeneca Pharmaceuticals LP provided publication support to Parexel for preparation of a manuscript. Spouse employee and stockholder of Janssen Pharmaceuticals. R.W.L. Honoraria for speaking/advising/consulting, and/or received research funds: AstraZeneca, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson and Johnson, Lundbeck, Lundbeck Institute, Pfizer, Servier, St. Jude Medical, Takeda University, Health Network Foundation, and Vancouver Coastal Health Research Institute. R.M. Investigator Janssen trials of esketamine; ‘paid-for’ ketamine clinic operated by Oxford Health NHS Foundation Trust - fees used to support the Trust. M.J.O. Consultant: Sunovion and Acadia Pharmaceuticals. Full-time employee of U.S. Department of Veterans Affairs. M.E.T. Advisory/Consultant: Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb Company, Cerecor inc., Eli Lilly & Co., Forest Laboratories, Gerson Lehrman Group, Fabre-Kramer Pharmaceuticals, Inc., GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante Inc., Merck and Co. Inc. (formerly Schering Plough and Organon), Moksha8, Naurex Inc., Neuronetics Inc., Novartis, Ortho-McNeil Pharmaceuticals (Johnson & Johnson; Janssen), Otsuka, Pamlab, L.L.C. (Nestle), Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Shire US Inc., Sunovion Pharmaceuticals Inc., Trius Therapeutical Inc. and Takeda. Grant support: Agency for Healthcare Research and Quality, Alkermes, AssureRx, Avanir, Forest Pharmaceuticals, Janssen, National Institute of Mental Health, and Otsuka Pharmaceuticals. Speakers Bureau: None since June, 2010. Equity Holdings: MedAvante, Inc. Royalties: American Psychiatric Foundation, Guilford

  11. 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

  12. 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

  13. 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…

  14. The depressogenic-like effect of acute and chronic treatment with dexamethasone and its influence on the activity of antidepressant drugs in the forced swim test in adult mice.

    PubMed

    Wróbel, Andrzej; Serefko, Anna; Wlaź, Piotr; Poleszak, Ewa

    2014-10-01

    There is a close relationship between chronic stress, glucocorticoids and depression. Psychiatric and cognitive symptoms resembling major depression have been observed in patients experiencing elevated glucocorticoid levels, and a high percentage of people suffering from depression have undergone a stressful event/events prior to the onset of this mental disorder. In our study, we investigated whether acute and chronic treatment of dexamethasone induces depression-like behavior in mice and if dexamethasone therapy influences the activity of antidepressant drugs with diverse modes of action. The antidepressant-like effect was assessed by the forced swim test in adult mice. The depressogenic-like activity of dexamethasone turned out to be dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64μg/kg) given as a single injection increased immobility time, whereas 16μg/kg/day of dexamethasone (but not 4μg/kg/day) administered repeatedly induced a significant alteration in animal behavior. These depressogenic doses of dexamethasone (i.e., 64μg/kg and 16μg/kg/day for an acute and repeated administration, respectively) diminished the antidepressant potential of the therapeutic doses of imipramine (10mg/kg), amitriptyline (10mg/kg), tianeptine (25mg/kg), mianserin (10mg/kg), citalopram (15mg/kg) and moclobemide (25mg/kg). Two main findings of our study should be particularly underlined: (1) both single and repeated administration of dexamethasone evoked a depression-like behavior of mice, (2) both single and repeated administration of dexamethasone were able to modify the activity of the antidepressant agents from various pharmacological groups, which may lead to a considerable reduction in the efficacy of pharmacotherapy prescribed for patients with mood disorders. PMID:24984273

  15. The depressogenic-like effect of acute and chronic treatment with dexamethasone and its influence on the activity of antidepressant drugs in the forced swim test in adult mice.

    PubMed

    Wróbel, Andrzej; Serefko, Anna; Wlaź, Piotr; Poleszak, Ewa

    2014-10-01

    There is a close relationship between chronic stress, glucocorticoids and depression. Psychiatric and cognitive symptoms resembling major depression have been observed in patients experiencing elevated glucocorticoid levels, and a high percentage of people suffering from depression have undergone a stressful event/events prior to the onset of this mental disorder. In our study, we investigated whether acute and chronic treatment of dexamethasone induces depression-like behavior in mice and if dexamethasone therapy influences the activity of antidepressant drugs with diverse modes of action. The antidepressant-like effect was assessed by the forced swim test in adult mice. The depressogenic-like activity of dexamethasone turned out to be dose-dependent: only the highest tested dose of the glucocorticoid (i.e., 64μg/kg) given as a single injection increased immobility time, whereas 16μg/kg/day of dexamethasone (but not 4μg/kg/day) administered repeatedly induced a significant alteration in animal behavior. These depressogenic doses of dexamethasone (i.e., 64μg/kg and 16μg/kg/day for an acute and repeated administration, respectively) diminished the antidepressant potential of the therapeutic doses of imipramine (10mg/kg), amitriptyline (10mg/kg), tianeptine (25mg/kg), mianserin (10mg/kg), citalopram (15mg/kg) and moclobemide (25mg/kg). Two main findings of our study should be particularly underlined: (1) both single and repeated administration of dexamethasone evoked a depression-like behavior of mice, (2) both single and repeated administration of dexamethasone were able to modify the activity of the antidepressant agents from various pharmacological groups, which may lead to a considerable reduction in the efficacy of pharmacotherapy prescribed for patients with mood disorders.

  16. Therapeutic monitoring of treatment with antidepressants.

    PubMed

    Bourin, M S; Kergueris, M F; Lapierre, Y D

    1989-09-01

    The present status of the relationship between blood plasma concentrations of tricyclic antidepressants and clinical outcome is reviewed. Plasma levels of imipramine, desmethylimipramine and nortriptyline are generally accepted as useful clinically but it is more difficult to establish a well-defined relationship between clomipramine and amitriptyline blood levels and clinical outcome. These assays are clinically relevant, particularly in cases of treatment failure, but also in the treatment of the elderly and of overdosage. The technical problems of the assay have practically been solved with the development of new analytic methods.

  17. Lateral Diffusion of Gαs in the Plasma Membrane Is Decreased after Chronic but not Acute Antidepressant Treatment: Role of Lipid Raft and Non-Raft Membrane Microdomains

    PubMed Central

    Czysz, Andrew H; Schappi, Jeffrey M; Rasenick, Mark M

    2015-01-01

    GPCR signaling is modified both in major depressive disorder and by chronic antidepressant treatment. Endogenous Gαs redistributes from raft- to nonraft-membrane fractions after chronic antidepressant treatment. Modification of G protein anchoring may participate in this process. Regulation of Gαs signaling by antidepressants was studied using fluorescence recovery after photobleaching (FRAP) of GFP-Gαs. Here we find that extended antidepressant treatment both increases the half-time of maximum recovery of GFP-Gαs and decreases the extent of recovery. Furthermore, this effect parallels the movement of Gαs out of lipid rafts as determined by cold detergent membrane extraction with respect to both dose and duration of drug treatment. This effect was observed for several classes of compounds with antidepressant activity, whereas closely related molecules lacking antidepressant activity (eg, R-citalopram) did not produce the effect. These results are consistent with previously observed antidepressant-induced translocation of Gαs, but also suggest an alternate membrane attachment site for this G protein. Furthermore, FRAP analysis provides the possibility of a relatively high-throughput screening tool for compounds with putative antidepressant activity. PMID:25249058

  18. Lateral diffusion of Gαs in the plasma membrane is decreased after chronic but not acute antidepressant treatment: role of lipid raft and non-raft membrane microdomains.

    PubMed

    Czysz, Andrew H; Schappi, Jeffrey M; Rasenick, Mark M

    2015-02-01

    GPCR signaling is modified both in major depressive disorder and by chronic antidepressant treatment. Endogenous Gαs redistributes from raft- to nonraft-membrane fractions after chronic antidepressant treatment. Modification of G protein anchoring may participate in this process. Regulation of Gαs signaling by antidepressants was studied using fluorescence recovery after photobleaching (FRAP) of GFP-Gαs. Here we find that extended antidepressant treatment both increases the half-time of maximum recovery of GFP-Gαs and decreases the extent of recovery. Furthermore, this effect parallels the movement of Gαs out of lipid rafts as determined by cold detergent membrane extraction with respect to both dose and duration of drug treatment. This effect was observed for several classes of compounds with antidepressant activity, whereas closely related molecules lacking antidepressant activity (eg, R-citalopram) did not produce the effect. These results are consistent with previously observed antidepressant-induced translocation of Gαs, but also suggest an alternate membrane attachment site for this G protein. Furthermore, FRAP analysis provides the possibility of a relatively high-throughput screening tool for compounds with putative antidepressant activity. PMID:25249058

  19. Augmentation with antidepressants in schizophrenia treatment: benefit or risk

    PubMed Central

    Mao, Ye-Meng; Zhang, Ming-Dao

    2015-01-01

    We focused on the application of antidepressants in schizophrenia treatment in this review. Augmentation of antidepressants with antipsychotics is a common clinical practice to treat resistant symptoms in schizophrenia, including depressive symptoms, negative symptoms, comorbid obsessive–compulsive symptoms, and other psychotic manifestations. However, recent systematic review of the clinical effects of antidepressants is lacking. In this review, we have selected and summarized current literature on the use of antidepressants in patients with schizophrenia; the patterns of use and effectiveness, as well as risks and drug–drug interactions of this clinical practice are discussed in detail, with particular emphasis on the treatment of depressive symptoms in schizophrenia. PMID:25834445

  20. Antidepressant Effects of Mallotus oppositifolius in Acute Murine Models

    PubMed Central

    Kukuia, Kennedy K. E.; Mante, Priscilla K.; Ameyaw, Elvis O.; Adongo, Donatus W.

    2014-01-01

    Objective. Hydroalcoholic extract of leaves of Mallotus oppositifolius (MOE), a plant used for CNS conditions in Ghana, was investigated for acute antidepressant effects in the forced swimming (FST) and tail suspension tests (TST). Results. In both FST and TST, MOE (10, 30, and 100 mg kg−1) significantly decreased immobility periods and frequencies. A 3-day pretreatment with 200 mg kg−1, i.p., para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, reversed the decline in immobility and the increase of swimming score induced by MOE in the modified FST. Pretreatment with reserpine alone (1 mg kg−1), α-methyldopa alone (400 mg kg−1, i.p.), or a combination of both drugs failed to reverse the decline in immobility or the increase in swimming score caused by the extract in the modified FST. The extract potentiated the frequency of head twitch responses induced by 5-hydroxytryptamine. Pretreatment with d-serine (600 mg kg−1, i.p.), glycine/NMDA agonist, abolished the behavioural effects of MOE while d-cycloserine (2.5 mg kg−1, i.p.), a glycine/NMDA partial agonist, potentiated it in both TST and modified FST. Conclusion. The extract exhibited antidepressant effects in mice which is mediated by enhancement of serotoninergic neurotransmission and inhibition of glycine/NMDA receptor activation. PMID:25045543

  1. 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

  2. Antidepressant Use During Pregnancy: Current Controversies and Treatment Strategies

    PubMed Central

    Payne, Jennifer L.; Meltzer-Brody, Samantha

    2009-01-01

    The treatment of depression during pregnancy is both a common and complex clinical challenge. The decision to expose the fetus to antidepressant medication during pregnancy must be weighed against the risks of untreated maternal depression to both mother and fetus. Maternal depression during pregnancy has been associated with increased rates of preterm birth and maternal substance use. The safety of antidepressant use during pregnancy appears to be largely reassuring but there remain two areas of controversy including neonatal withdrawal syndrome and primary pulmonary hypertension of the newborn (PPHN). Individualized treatment recommendations based on the patient's history are essential in order to optimize outcomes. PMID:19661762

  3. Epigenetic alterations in depression and antidepressant treatment.

    PubMed

    Menke, Andreas; Binder, Elisabeth B

    2014-09-01

    Epigenetic modifications control chromatin structure and function, and thus mediate changes in gene expression, ultimately influencing protein levels. Recent research indicates that environmental events can induce epigenetic changes and, by this, contribute to long-term changes in neural circuits and endocrine systems associated with altered risk for stress-related psychiatric disorders such as major depression. In this review, we describe recent approaches investigating epigenetic modifications associated with altered risk for major depression or response to antidepressant drugs, both on the candidate gene levels as well as the genome-wide level. In this review we focus on DNA methylation, as this is the most investigated epigenetic change in depression research.

  4. Antidepressant-associated sexual dysfunction: impact, effects, and treatment.

    PubMed

    Higgins, Agnes; Nash, Michael; Lynch, Aileen M

    2010-01-01

    Sexual dysfunction is a common side effect of antidepressants and can have significant impact on the person's quality of life, relationships, mental health, and recovery. The reported incidence of sexual dysfunction associated with antidepressant medication varies considerably between studies, making it difficult to estimate the exact incidence or prevalence. The sexual problems reported range from decreased sexual desire, decreased sexual excitement, diminished or delayed orgasm, to erection or delayed ejaculation problems. There are a number of case reports of sexual side effects, such as priapism, painful ejaculation, penile anesthesia, loss of sensation in the vagina and nipples, persistent genital arousal and nonpuerperal lactation in women. The focus of this article is to explore the incidence, pathophysiology, and treatment of antidepressant iatrogenic sexual dysfunction. PMID:21701626

  5. New antidepressants in the treatment of neuropathic pain. A review.

    PubMed

    Mattia, C; Paoletti, F; Coluzzi, F; Boanelli, A

    2002-03-01

    Before 1980s, tricyclics (TCAs) were considered, between antidepressants, the standard in the treatment of different kinds of neuropathic pain, for their action on noradrenergic and serotoninergic pathways, thought the high incidence of side effects. In 1980s a new class of antidepressants has been introduced, the selective serotonin reuptake inhibitors (SSRI). We reviewed some publications, including trials comparing SSRIs with TCAs in pain management. The available literature did not show an effective superiority of the former on the latter, though improved side-effect profile. Recently new antidepressants were introduced in the clinical use, with a significant reduction in side effects and equivalent efficacy on mood disorders. These new drugs may be classified in three categories: Serotonin and Noradrenergic Reuptake Inhibitors (SNaRI), like venlafaxine and nefazodone; Noradrenergic and Specific Serotoninergic Antidepressants (NaSSA), like mirtazapine, and Noradrenaline Reuptake Inhibitors (NaRI), like reboxetine. In this review we present the available publications of their application in the treatment of neuropathic pain. Venlafaxine (SNaRI), the most investigated of these new drugs, was shown to be effective in the treatment of different kinds of pain, with side-effects profile significantly better than TCAs. The other new antidepressants have been less extensively studied, thus only anecdotal therapeutic results and experimental works have been found and reported. Existing data are surely insufficient to conclude which of these new classes of drugs has the best clinical profile and can be more effective in the treatment of neuropathic pain, but the lower incidence of side effects should be considered. Further evidence-based research in the safety and efficacy of these promising agents in pain relief, is warranted. PMID:11981519

  6. Postsynaptic serotonergic blockade following chronic antidepressive treatment with trazodone in an animal model of depression.

    PubMed

    Hingtgen, J N; Hendrie, H C; Aprison, M H

    1984-03-01

    Acute pretreatment with clinically equivalent doses of antidepressive drugs has been observed to block D,L-5-hydroxytryptophan (5-HTP) induced behavioral depression in rats working on a food-reinforced operant schedule. Data from studies designed to distinguish presynaptic from postsynaptic events, indicated that the antidepressants were acting in part as blockers of postsynaptic serotonergic receptors. Using the same 5-HTP model of depression, we studied both the chronic and acute effects of a recently introduced antidepressant, triazolopyridine compound. Rats working for milk reinforcement and exhibiting behavioral depression following administration of 50 mg/kg 5-HTP were pretreated (one hr before 5-HTP) with 1, 2, or 4 mg/kg trazodone with resulting blockade of 5-HTP induced depression of 35, 62 and 70% respectively. Chronic administration of trazodone (2 mg/kg trazodone/day) also resulted in a significant blockade of the 5-HTP effect (75%). Neither 2 mg/kg or 4 mg/kg trazodone was found to potentiate the shorter period of depression following 25 mg/kg 5-HTP. Chronic treatment with the antidepressant drugs, amitriptyline or mianserin also blocked 5-HTP depression. Thus, as in our earlier studies, these data suggest an important postsynaptic mechanism associated with chronic administration of trazodone, amitriptyline and mianserin which could be implicated in the therapeutic effectiveness of these drugs. The potency of trazodone in relation to other antidepressant drugs in our behavioral model of depression paralleled their potency in displacing radioligand binding to 5-HT receptors, and gives additional support for the new hypersensitive postsynaptic serotonin receptor theory of depression.

  7. 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

  8. Chronic Antidepressant Treatment Impairs the Acquisition of Fear Extinction

    PubMed Central

    Burghardt, Nesha S.; Sigurdsson, Torfi; Gorman, Jack M.; McEwen, Bruce S.; LeDoux, Joseph E.

    2012-01-01

    Background Like fear conditioning, the acquisition phase of extinction involves new learning that is mediated by the amygdala. During extinction training, the conditioned stimulus is repeatedly presented in the absence of the unconditioned stimulus and the expression of previously learned fear gradually becomes suppressed. Our previous study revealed that chronic treatment with a selective serotonin reuptake inhibitor (SSRI) impairs the acquisition of auditory fear conditioning. To gain further insight into how SSRIs affect fear learning, we tested the effects of chronic SSRI treatment on the acquisition of extinction. Methods Rats were treated chronically (22 days) or subchronically (9 days) with the SSRI citalopram (10 mg/kg/day) before extinction training. The results were compared to those following chronic and subchronic treatment with tianeptine (10 mg/kg/day), an antidepressant with a different method of action. The expression of the NR2B subunit of the NMDA receptor in the amygdala was examined after behavioral testing. Results Chronic but not subchronic administration of citalopram impaired the acquisition of extinction and downregulated the NR2B subunit of the NMDA receptor in the lateral and basal nuclei of the amygdala. Similar behavioral and molecular changes were found with tianeptine treatment. Conclusions These results provide further evidence that chronic antidepressant treatment can impair amygdala-dependent learning. Our findings are consistent with a role for glutamatergic neurotransmission in the final common pathway of antidepressant treatment. PMID:23260230

  9. 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

  10. Acute Exercise Improves Physical Sexual Arousal in Women Taking Antidepressants

    PubMed Central

    Lorenz, Tierney A.; Meston, Cindy M.

    2012-01-01

    Background Antidepressants can impair sexual arousal. Exercise increases genital arousal in healthy women, likely due to increasing sympathetic nervous system (SNS) activity. Purpose Test if exercise increases genital arousal in women taking antidepressants, including selective serotonin reuptake inhibitors (SSRIs), which suppress SNS activity, and selective serotonin and norepinephrine reuptake inhibitors (SNRIs), which suppress the SNS less. Method Women reporting antidepressant-related sexual arousal problems (N=47) participated in three counterbalanced sessions where they watched an erotic film while we recorded genital and SNS arousal. In two sessions, women exercised for 20 min, either 5 or 15 min prior to the films. Results During the no-exercise condition, women taking SSRIs showed significantly less genital response than women taking SNRIs. Exercise prior to sexual stimuli increased genital arousal in both groups. Women reporting greater sexual dysfunction had larger increases in genital arousal post-exercise. For women taking SSRIs, genital arousal was linked to SNS activity. Conclusions Exercise may improve antidepressant-related genital arousal problems. PMID:22403029

  11. 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

  12. Treatment of acute gout.

    PubMed

    Schlesinger, Naomi

    2014-05-01

    This article presents an overview of the treatment of acute gout. Nonpharmacologic and pharmacologic treatments, monotherapy versus combination therapy, suggested recommendations, guidelines for treatment, and drugs under development are discussed.

  13. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    PubMed

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. PMID:27089522

  14. Patients' perspectives on antidepressant treatment in consultations with physicians.

    PubMed

    Fosgerau, Christina Fogtmann; Davidsen, Annette Sofie

    2014-05-01

    Patient perspectives on antidepressant treatment and physician attention, and responses toward these in consultations with patients diagnosed with depression, are rarely studied. We analyzed video-recorded consultations with general practitioners (GPs) and psychiatrists. We used conversation analysis and systemic functional linguistics and found that the perspectives patients expressed related to the possibility of achieving, and the inability to retain, a sense of agency. Patients also presented indirect expressions of shame and expressions suggesting alienation toward medical treatment. GPs attended to patient perspectives by talking about medication indirectly. When patients expressed their perspectives, GPs responded by being nonauthoritative but also without prompting patients to elaborate on their reflections. Psychiatrists responded authoritatively and never urged patients to reflect on their perspectives. Shared decision making did not take place because physicians did not explore patients' perspectives in depth or offer their expertise by taking these perspectives into consideration.

  15. Antidepressant treatment in helpless rats: effect on the electrophysiological activity of raphe dorsalis serotonergic neurons.

    PubMed

    Maudhuit, C; Prévot, E; Dangoumau, L; Martin, P; Hamon, M; Adrien, J

    1997-04-01

    Chronic treatment with antidepressants renders serotonergic neuronal firing less sensitive to the inhibitory effect of serotonin (5-HT) reuptake blockers in the rat, and this has been considered as a major correlate of the therapeutic action of these drugs. We investigated whether the same mechanisms could be evidenced in an experimental model of depression, the learned helplessness paradigm. Rats rendered helpless by a single session of inescapable electrical footshocks exhibit, for several days, depression-like behavioural deficits which can be reversed by sub-chronic, but not acute, treatment with antidepressants. Recording of serotonergic neurons in the dorsal raphe nucleus revealed that, under baseline conditions, the spontaneous firing was similar in helpless rats and in non-helpless controls. However, neurons in the former group exhibited an enhanced sensitivity to the inhibitory action of the 5-HT reuptake blocker, citalopram (ED50 = 0.18 +/- 0.02 mg/kg IV in helpless rats versus 0.27 +/- 0.03 mg/kg IV in controls, P < 0.05). Treatment with zimeldine during 3 consecutive days induced in both helpless and control rats, a decrease in the inhibitory response of serotonergic neurons to the citalopram challenge, which resulted in a normalization of the neuronal reactivity in the helpless group (ED50 = 0.31 +/- 0.03 mg/kg IV). Since this adaptive phenomenon parallels the behavioural improvement induced by the repeated administration of zimeldine and other antidepressants in helpless rats, it might be considered as a crucial event in the mechanism of therapeutic action of these drugs.

  16. Antidepressant treatment reduces Fos-like immunoreactivity induced by swim stress in different columns of the periaqueductal gray matter.

    PubMed

    Lino-de-Oliveira, Cilene; de Oliveira, Rúbia M W; Pádua Carobrez, Antonio; de Lima, Thereza C M; del Bel, Elaine Aparecida; Guimarães, Francisco Silveira

    2006-10-16

    Antidepressant treatment attenuates behavioral changes induced by uncontrollable stress. The periaqueductal gray matter (PAG) is proposed to be a brain site involved in the behavioral responses to uncontrollable stress and antidepressant effects. The main goal of the present study was to investigate the effect of antidepressant treatment on the pattern of neural activation of the PAG along its mediolateral and rostrocaudal subregions after a forced swim stress episode. Male Wistar rats were sub-acutely treated with desipramine (a selective noradrenaline re-uptake blocker, three injections of 10 mg/kg in 24 h) or clomipramine (a non-selective serotonin and noradrenaline re-uptake blocker, three injections of 10 mg/kg in 24 h) and submitted to the forced swimming test (FST). Two hours after the test their brain were removed for Fos immunohistochemistry. Fos-like immunoreactivity (FLI) in rostral, intermediate and caudal portions of dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG) PAG were quantified by a computerized system. The FST session increased FLI in most parts of the PAG. Previous treatment with desipramine or clomipramine reduced FLI in all columns of the PAG. FLI in the PAG correlated positively with to the immobility time and negatively with to climbing behavior scored during the test. These results indicate that neurons in the PAG are activated by uncontrollable stress. Moreover, inhibitory action of antidepressants on this activity may be associated with the anti-immobility effects of these drugs in the FST.

  17. Chronic Antidepressant Treatment in Normal Mice Induces Anxiety and Impairs Stress-coping Ability

    PubMed Central

    Baek, In-Sun; Park, Jin-Young

    2015-01-01

    Antidepressants are clinically used for patients with major depression. Antidepressant treatments in certain groups of patients are effective for relieving depression as well as anxiety disorder. However, it is not clearly known whether the use of current antidepressants in healthy persons is beneficial for upcoming depression- and anxiety-inducing life events. To address this question, normal mice were intraperitoneally administered with imipramine or fluoxetine for more than 2 weeks, and behaviors related to anxiety and depression were evaluated. Mice treated with imipramine or fluoxetine for more than 14 days exhibited significantly decreased immobility time in the forced swim test and tail suspension test, but these mice exhibited enhanced anxiety in several behavioral tests. Furthermore, chronic antidepressant treatments followed by sub-threshold level of stress in normal mice profoundly aggravated antidepressant-induced anxiety-like behaviors without further affecting depression-related behaviors. Chronic antidepressant treatments followed by sub-threshold level of stress produced swollen vesicles and ulcerations on the lips as well as a watery and inflammatory nose. Mice given chronic antidepressant treatments displayed intestinal abnormalities evidenced by a highly enlarged and inflamed small intestine full of defecation materials. These results suggest that chronic antidepressant treatment in normal mice provokes anxiety-like behaviors and impairs their stress-coping ability. PMID:26113795

  18. Pharmacogenetics of antidepressant treatment in obsessive-compulsive disorder: an update and implications for clinicians.

    PubMed

    Zai, Gwyneth; Brandl, Eva J; Müller, Daniel J; Richter, Margaret A; Kennedy, James L

    2014-06-01

    Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder with high genetic influence. Antidepressants such as serotonin reuptake inhibitors, are widely accepted as the first-line medications for OCD; however, approximately 50% of OCD patients show poor response. Personalized medicine utilizing genetic testing has recently received much attention because the variability of antidepressant response and tolerability are partly due to an individual's genetic variations. This has led to researchers investigating the role of specific genetic factors on antidepressant response and utility of testing in the clinical realm. Genetic test panels are showing promise for guiding antidepressant treatment to improve outcomes in depression. This article will review the most recent findings in the pharmacogenetics of OCD and its related disorders. Promising results have been reported for several serotonergic and glutamatergic system genes and the cytochrome CYP450 liver enzyme genes, which appear to play an important role in OCD and antidepressant response.

  19. The Antidepressant Treatment Response Index as a Predictor of Reboxetine Treatment Outcome in Major Depressive Disorder.

    PubMed

    Caudill, Marissa M; Hunter, Aimee M; Cook, Ian A; Leuchter, Andrew F

    2015-10-01

    Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

  20. Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance.

    PubMed

    Bigio, Benedetta; Mathé, Aleksander A; Sousa, Vasco C; Zelli, Danielle; Svenningsson, Per; McEwen, Bruce S; Nasca, Carla

    2016-07-12

    Although regulation of energy metabolism has been linked with multiple disorders, its role in depression and responsiveness to antidepressants is less known. We found that an epigenetic and energetic agent, acetyl-l-carnitine (LAC, oral administration), rapidly rescued the depressive- and central and systemic metabolic-like phenotype of LAC-deficient Flinders Sensitive Line rats (FSL). After acute stress during LAC treatment, a subset of FSL continued to respond to LAC (rFSL), whereas the other subset did not (nrFSL). RNA sequencing of the ventral dentate gyrus, a mood-regulatory region, identified metabolic factors as key markers predisposing to depression (insulin receptors Insr, glucose transporters Glut-4 and Glut-12, and the regulator of appetite Cartpt) and to LAC responsiveness (leptin receptors Lepr, metabotropic glutamate receptors-2 mGlu2, neuropeptide-Y NPY, and mineralocorticoid receptors MR). Furthermore, we found that stress-induced treatment resistance in nrFSL shows a new gene profile, including the metabolic regulator factors elongation of long chain fatty acids 7 (Elovl7) and cytochrome B5 reductase 2 (Cyb5r2) and the synaptic regulator NPAS4. Finally, while improving central energy regulation and exerting rapid antidepressant-like effects, LAC corrected a systemic hyperinsulinemia and hyperglicemia in rFSL and failed to do that in nrFSL. These findings establish CNS energy regulation as a factor to be considered for the development of better therapeutics. Agents such as LAC that regulate metabolic factors and reduce glutamate overflow could rapidly ameliorate depression and could also be considered for treatment of insulin resistance in depressed subjects. The approach here serves as a model for identifying markers and underlying mechanisms of predisposition to diseases and treatment responsiveness that may be useful in translation to human behavior and psychopathology. PMID:27354525

  1. 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

  2. [The current concept of augmentation of treatment efficiency with antidepressant medication].

    PubMed

    Damulin, I V; Suvorova, I A

    2015-01-01

    The introduction into clinical practice of new and highly effective antidepressants has certainly helped to resolve the problem of depression therapy. However, achieving a complete remission, which is a key point for therapy in depressed patients, remains a difficult task. It is known that a significant number of patients do not respond to antidepressants. So, special attention has been paid in recent years towards investigation of methods that could improve the treatment effectiveness in depressive. In this review presents the results of clinical trials of buspirone as an adjunctive therapy in cases with previous ineffective use of antidepressants in patients with major depressive disorder.

  3. 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

  4. Treatment Resistant Depression with Loss of Antidepressant Response: Rapid—Acting Antidepressant Action of Dextromethorphan, A Possible Treatment Bridging Molecule

    PubMed Central

    Lauterbach, Edward C.

    2016-01-01

    Dextromethorphan (DM) may have ketamine—like rapid—acting, treatment—resistant, and conventional antidepressant effects.1,2 This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment—resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid—acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days. Upon full relapse in DSM-5 MDD while taking 600 mg/day of the strong CYP2D6 inhibitor bupropion XL, a 300 mg oral loading dose of DM was given, followed by 60 mg po bid after an additional dose—finding period, without side effects. DM exhibited a ketamine—like rapid—acting antidepressant effect, thought to be mediated by mTOR activation (related to NMDA PCP site antagonism, sigma-1 and beta adrenergic receptor stimulation) and 5HTT inhibition, resulting in AMPA receptor trafficking, and dendritogenesis, spinogenesis, synaptogenesis, and increased neuronal survival (related to NMDA antagonism and sigma-1 and mTOR signaling). This report appears to be the first report of a rapid—acting effect in unipolar MDD and adds to antidepressant effects observed in the retrospective chart review of 77 patients with Bipolar II Disorder (Kelly and Lieberman 2014). If replicated, there is some reason to think that the administration of other agents with DM, such as lithium or D-cycloserine, might prolong the duration of the rapid-antidepressant effect. PMID:27738380

  5. [The effectiveness of antidepressants in the treatment of chronic non-cancer pain--a review].

    PubMed

    Miller, Adam; Rabe-Jabłońska, Jolanta

    2005-01-01

    Antidepressants are often applied in the treatment of chronic pain. Analgesic action of tricyclic antidepressants (TCAs) has been extensively studied and proven. TCAs are associated with a number of adverse effects which are inconvenient for patients. The newer antidepressants have fewer side effects and equivalent efficacy on mood disorders. This article reviews the available publications (mainly placebo-controlled trials) concerning the efficacy of these medications in the treatment of chronic pain. The data regarding selective serotonin reuptake inhibitors (SSRI) are conflicting. Trazodone (a serotonin-reuptake inhibitor as well as a postsynaptic serotonin receptor antagonist) does not appear to be effective for the treatment of chronic pain. No placebo-controlled studies are available for noradrenergic and specific serotoninergic antidepressant (NaSSA)--mirtazapine and noradrenaline reuptake inhibitor (NaRI)--reboxetine. Bupropion, a noradrenaline and dopamine-reuptake inhibitor appears to be effective in the treatment of neuropathic pain. Venlafaxine--selective serotonin and noradrenergic reuptake inhibitors (SNRI) was shown to be effective in the treatment of different kinds of pain. Duloxetine (SNRI) is effective in relieving both the emotional and painful physical symptoms of depression. Additional randomized, controlled trials are necessary to fully evaluate the role of new antidepressants in the treatment of chronic pain. PMID:15771151

  6. [Αnti-Inflammatory medication as adjunctive antidepressive treatment].

    PubMed

    Boufidou, F; Nikolaou, C

    2016-01-01

    Mounting data of evidence that have emerged during the last twenty years, point towards the existence of an inflammatory mechanism underlying the pathophysiology of depressive disorder. These data have inspired a number of clinical studies characterized by the administration of inflammatory response altering medication in addition to conventional medication in depressive disorder patients. The drugs were either Non Steroid Anti-inflammatory Drugs (NSAIDs) or Tumor Necrosis Factor-alpha (TNFa) inhibitors and were selected among those that are already in use for various diseases related to the immune system. The choice of these specific immunomodulatory agents for the co-administration with conventional antidepressive medication was based on a number of laboratory data and clinical evidence. A total of seven relevant clinical trials have been conducted, all of them with promising results that have been published between 2006 and 2013. However, only four out of them were eligibly designed regarding the homogeneity of the study groups, randomization, double-blinding and placebo controlling. These three studies showed clinical advantages of the adjunctive medication as estimated by significant drops in Hamilton scores. Of interest are the findings of the most recent and largest clinical trial of the TNF-a antagonist infliximab which show that treatment with anti-inflammatory agents may be beneficial only in depressive patients with raised levels of baseline inflammatory markers. A limitation of the studies was that, since no guidelines currently exist for anti-inflammatory agents and depression, adjunctive medication could have been under or overdosed. Other limitations were the follow-up period that was rather small and the number of the participants that was also small. Recently, a lot of progress has been made in identifying therapeutic targets along metabolic pathways in the brain relevant to depression, which could be manipulated by immune mediators. In fact

  7. The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment

    PubMed Central

    Pringle, Abbie; Harmer, Catherine J.

    2015-01-01

    Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients. PMID:26869848

  8. The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment.

    PubMed

    Pringle, Abbie; Harmer, Catherine J

    2015-12-01

    Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.

  9. 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

  10. Out of the Black Box: Treatment of Resistant Depression in Adolescents and the Antidepressant Controversy

    PubMed Central

    Asarnow, Joan Rosenbaum; Vitiello, Benedetto; Clarke, Gregory; Keller, Martin; Emslie, Graham J.; Ryan, Neal; Porta, Giovanna; Iyengar, Satish; Ritz, Louise; Zelanzny, Jamie; Onorato, Matthew; Brent, David

    2012-01-01

    Abstract Objective The purpose of this article is to describe the effects of the pediatric antidepressant controversy on the Treatment of Serotonin-Selective Reuptake Inhibitor (SSRI) Resistant Depression in Adolescents (TORDIA) trial. Method Adolescents, ages 12–18 years, with SSRI resistant depression were randomized to one of four treatments for a 12 week trial: Switch to different SSRI, switch to an alternate antidepressant (venlafaxine), switch to an alternate SSRI plus cognitive behavior therapy (CBT), or switch to venlafaxine plus CBT. Results The health advisories and “black box” warnings regarding suicidality and antidepressants in adolescents occurred during the course of the TORDIA trial. Revisions to the protocol, multiple-consent form changes, and re-consenting of patients were necessary. Recruitment of participants was adversely affected. Conclusion Despite a cascade of unforeseen events that delayed the completion of the study, the TORDIA trial resulted in clinically important information about treatment-resistant depression in adolescents. PMID:22251022

  11. Tianeptine treatment induces antidepressive-like effects and alters BDNF and energy metabolism in the brain of rats.

    PubMed

    Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Ribeiro, Karine F; Antunes, Altamir R; Scaini, Giselli; Jeremias, Isabela C; dos Santos, Lis Mairá M; Jeremias, Gabriela C; Streck, Emilio L; Quevedo, João

    2012-08-01

    The present study was aimed at investigating the behavioral and molecular effects of tianeptine. To this aim, Wistar rats were treated with tianeptine (5, 10 and 15 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The results showed that both treatments reduced the immobility time. The BDNF levels were increased in the prefrontal cortex with tianeptine and decreased in the nucleus accumbens after acute treatment; in chronic treatment, BDNF levels were increased in the prefrontal and hippocampus with tianeptine. Acute treatment decreased the citrate synthase activity in the prefrontal cortex with tianeptine, and increased it in the amygdala with imipramine; chronic treatment increased the citrate synthase in the hippocampus with tianeptine. The creatine kinase was increased in the prefrontal cortex with tianeptine and in the amygdala with imipramine after acute treatment; chronic treatment increased the creatine kinase activity in the hippocampus with imipramine and tianeptine. The complex I activity was decreased in the prefrontal cortex with imipramine and increased in the hippocampus with tianeptine. The other complexes were increased with imipramine and tianeptine at all doses, but were related to the treatment given and the brain area studied. Chronic treatment increased the malate dehydrogenase activity in the amygdala with tianeptine. Acute treatment decreased the succinate activity in the prefrontal cortex, hippocampus and amygdala with tianeptine; chronic treatment increased the succinate activity in the hippocampus with tianeptine at all doses. In conclusion, tianeptine exerted antidepressant-like behavior which can be attributed to its effects on pathways related to depression, such as BDNF and metabolism energy.

  12. Tianeptine treatment induces antidepressive-like effects and alters BDNF and energy metabolism in the brain of rats.

    PubMed

    Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Ribeiro, Karine F; Antunes, Altamir R; Scaini, Giselli; Jeremias, Isabela C; dos Santos, Lis Mairá M; Jeremias, Gabriela C; Streck, Emilio L; Quevedo, João

    2012-08-01

    The present study was aimed at investigating the behavioral and molecular effects of tianeptine. To this aim, Wistar rats were treated with tianeptine (5, 10 and 15 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The results showed that both treatments reduced the immobility time. The BDNF levels were increased in the prefrontal cortex with tianeptine and decreased in the nucleus accumbens after acute treatment; in chronic treatment, BDNF levels were increased in the prefrontal and hippocampus with tianeptine. Acute treatment decreased the citrate synthase activity in the prefrontal cortex with tianeptine, and increased it in the amygdala with imipramine; chronic treatment increased the citrate synthase in the hippocampus with tianeptine. The creatine kinase was increased in the prefrontal cortex with tianeptine and in the amygdala with imipramine after acute treatment; chronic treatment increased the creatine kinase activity in the hippocampus with imipramine and tianeptine. The complex I activity was decreased in the prefrontal cortex with imipramine and increased in the hippocampus with tianeptine. The other complexes were increased with imipramine and tianeptine at all doses, but were related to the treatment given and the brain area studied. Chronic treatment increased the malate dehydrogenase activity in the amygdala with tianeptine. Acute treatment decreased the succinate activity in the prefrontal cortex, hippocampus and amygdala with tianeptine; chronic treatment increased the succinate activity in the hippocampus with tianeptine at all doses. In conclusion, tianeptine exerted antidepressant-like behavior which can be attributed to its effects on pathways related to depression, such as BDNF and metabolism energy. PMID:22659397

  13. Effect of chronic treatment with the antidepressant tianeptine on the hypothalamo-pituitary-adrenal axis.

    PubMed

    Delbende, C; Tranchand Bunel, D; Tarozzo, G; Grino, M; Oliver, C; Mocaër, E; Vaudry, H

    1994-01-14

    The effects of acute and chronic administration of tianeptine, a novel antidepressant agent, on the hypothalamo-pituitary-adrenal axis were studied in the adult male rat. A single injection of tianeptine did not alter the activity of the hypothalamo-pituitary-adrenal axis. In contrast, chronic administration of tianeptine (10 mg/kg twice a day for 15 days) induced a significant decrease in the concentration of corticotropin-releasing factor (CRF) in the hypothalamus and adrenocorticotropin (ACTH) in the anterior lobe of the pituitary. Chronic tianeptine treatment did not modify CRF levels in the cerebral cortex and hippocampus, and did not alter alpha-melanocyte-stimulating hormone and beta-endorphin levels in the neurointermediate lobe of the pituitary. Using the in situ hybridization technique, we observed that chronic administration of tianeptine did not modify CRF mRNA levels in the paraventricular nucleus of the hypothalamus. The effect of chronic tianeptine treatment on the neuroendocrine response to stress was also investigated. Tube restraint stress for 30 min induced a significant depletion of hypothalamic CRF and a substantial increase of plasma ACTH and corticosterone. Tianeptine abolished the stress-induced reduction of hypothalamic CRF concentration and markedly reduced the stress-induced increase in plasma ACTH and corticosterone levels. Taken together, these results suggest that tianeptine acts primarily at the level of the hypothalamus: (1) in unstressed rats, tianeptine reduces hypothalamic CRF and pituitary ACTH contents; (2) in stressed animals, tianeptine attenuates the activation of the hypothalamo-pituitary-adrenal axis.

  14. A cognitive deficit induced in rats by chronic intermittent cold stress is reversed by chronic antidepressant treatment

    PubMed Central

    Danet, M.; Lapiz-Bluhm, S.; Morilak, David A.

    2010-01-01

    We have previously reported that 14-days of chronic intermittent cold (CIC) stress induced a cognitive deficit in reversal learning on the rat attentional set-shifting test. This effect may be related to dysregulation of 5-HT function in orbitofrontal cortex, as a model of cognitive dysfunction in depression. To test the ability of chronic antidepressant drug treatment to reverse the cognitive deficit induced by CIC, it was first necessary to assess the temporal characteristics of the CIC-induced cognitive deficit. Thus, in the first study, we assessed the duration of the cognitive deficit following 2-weeks CIC stress. Replicating previous experiments, CIC induced a reversal learning deficit tested 3 days after the last cold exposure. However, cognitive performance of CIC-stressed rats was no different from unstressed controls when tested 7, 14 or 21 days after termination of the stress treatment. We next compared behavior 3 days after 2-weeks CIC to that seen 3 days after 5-weeks CIC, and found similar deficits in reversal learning. Thus, in the final study, antidepressant drug treatment was initiated after 2-weeks of CIC stress, and was maintained for 3 weeks, concurrent with the continuation of CIC stress. Both chronic and acute treatment with the selective serotonin reuptake inhibitor, citalopram, but not the norepinephrine reuptake blocker, desipramine, reversed the cognitive deficit induced by CIC stress. Thus, this stress-induced cognitive deficit may be a useful model for cognitive deficits related to prefrontal cortical hypoactivity in depression, and for investigating neurobiological mechanisms underlying the beneficial effects of chronic antidepressant drug treatment. PMID:20149267

  15. Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments

    PubMed Central

    Leuchter, Andrew F.; Hunter, Aimee M.; Krantz, David E.; Cook, Ian A.

    2015-01-01

    Treatments for major depressive disorder (MDD) act at different hierarchical levels of biological complexity, ranging from the individual synapse to the brain as a whole. Theories of antidepressant medication action traditionally have focused on the level of cell-to-cell interaction and synaptic neurotransmission. However, recent evidence suggests that modulation of synchronized electrical activity in neuronal networks is a common effect of antidepressant treatments, including not only medications, but also neuromodulatory treatments such as repetitive transcranial magnetic stimulation. Synchronization of oscillatory network activity in particular frequency bands has been proposed to underlie neurodevelopmental and learning processes, and also may be important in the mechanism of action of antidepressant treatments. Here, we review current research on the relationship between neuroplasticity and oscillatory synchrony, which suggests that oscillatory synchrony may help mediate neuroplastic changes related to neurodevelopment, learning, and memory, as well as medication and neuromodulatory treatment for MDD. We hypothesize that medication and neuromodulation treatments may have related effects on the rate and pattern of neuronal firing, and that these effects underlie antidepressant efficacy. Elucidating the mechanisms through which oscillatory synchrony may be related to neuroplasticity could lead to enhanced treatment strategies for MDD. PMID:25809789

  16. Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments.

    PubMed

    Leuchter, Andrew F; Hunter, Aimee M; Krantz, David E; Cook, Ian A

    2015-05-01

    Treatments for major depressive disorder (MDD) act at different hierarchical levels of biological complexity, ranging from the individual synapse to the brain as a whole. Theories of antidepressant medication action traditionally have focused on the level of cell-to-cell interaction and synaptic neurotransmission. However, recent evidence suggests that modulation of synchronized electrical activity in neuronal networks is a common effect of antidepressant treatments, including not only medications, but also neuromodulatory treatments such as repetitive transcranial magnetic stimulation. Synchronization of oscillatory network activity in particular frequency bands has been proposed to underlie neurodevelopmental and learning processes, and also may be important in the mechanism of action of antidepressant treatments. Here, we review current research on the relationship between neuroplasticity and oscillatory synchrony, which suggests that oscillatory synchrony may help mediate neuroplastic changes related to neurodevelopment, learning, and memory, as well as medication and neuromodulatory treatment for MDD. We hypothesize that medication and neuromodulation treatments may have related effects on the rate and pattern of neuronal firing, and that these effects underlie antidepressant efficacy. Elucidating the mechanisms through which oscillatory synchrony may be related to neuroplasticity could lead to enhanced treatment strategies for MDD.

  17. Utilization and mechanism of action of tricyclic antidepressants in the treatment of chronic facial pain: a review of the literature.

    PubMed Central

    Brown, R. S.; Bottomley, W. K.

    1990-01-01

    Tricyclic antidepressants show promise in the treatment of chronic facial pain. The antinociceptive activity of this class of drugs appears to be independent of any antidepressant effects. An hypothesis is proposed that tricyclics antidepressants activate a descending serotonergic (5-HT1) antinociceptive pathway which in turn influences endogenous opioids. This antinociceptive pathway appears to utilize an endogenous pain modulation system. Future studies may demonstrate the operative mechanisms of action and open understanding as to etiologic factors. PMID:2096745

  18. Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

    PubMed Central

    Wang, Yunfeng; Yu, Ting; Wang, Yun; Jiang, Liuqin; Lin, Lin

    2015-01-01

    Aim The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome. Methods We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis. Results Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups. Conclusions TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS. PMID:26252008

  19. The role of antidepressants in the treatment of abdominal obesity.

    PubMed

    Rosmond, R; Björntorp, P

    2000-06-01

    The pathophysiology of abdominal obesity is unclear and controversial. Recent evidence now suggests that inadequate cortisol secretion is associated with abnormalities in glucose, insulin and lipid metabolism, including hypertension, bringing the importance of the hypothalamic-pituitary-adrenal (HPA) axis in the pathogenesis of abdominal obesity to the forefront. In addition, abnormal gonadal steroid concentrations and impaired plasma growth hormone levels accompany the abdominally obese state. Since the reproductive and growth axes are inhibited at many levels by various components of the HPA axis, increasing cortisol levels results in further depression of testosterone and growth hormone concentrations. Over the last decade, antidepressant (serotoninergic) drugs have proved useful as equalizers of HPA axis hyperactivity. Such therapy may interrupt the vicious circle of a hyperactive HPA axis leading to increasing abdominal obesity and endocrine perturbations that, in turn, leads to progressive accumulation of abdominal fat. Additionally, preliminary results indicate that serotoninergic agents decrease abdominal fat mass with improvements in related risk factors.

  20. Degradation and acute toxicity removal of the antidepressant Fluoxetine (Prozac(®)) in aqueous systems by electron beam irradiation.

    PubMed

    Silva, Vanessa Honda Ogihara; Dos Santos Batista, Ana Paula; Silva Costa Teixeira, Antonio Carlos; Borrely, Sueli Ivone

    2016-06-01

    Electron beam irradiation (EBI) has been considered an advanced technology for the treatment of water and wastewater, whereas very few previous investigations reported its use for removing pharmaceutical pollutants. In this study, the degradation of fluoxetine (FLX), an antidepressant marketed as Prozac(®), was investigated by using EBI at FLX initial concentration of 19.4 ± 0.2 mg L(-1). More than 90 % FLX degradation was achieved at 0.5 kGy, with FLX below the detection limit (0.012 mg L(-1)) at doses higher than 2.5 kGy. The elucidation of organic byproducts performed using direct injection mass spectrometry, along with the results of ion chromatography, indicated hydroxylation of FLX molecules with release of fluoride and nitrate anions. Nevertheless, about 80 % of the total organic carbon concentration remained even for 7.5 kGy or higher doses. The decreases in acute toxicity achieved 86.8 and 9.6 % for Daphnia similis and Vibrio fischeri after EBI exposure at 5 kGy, respectively. These results suggest that EBI could be an alternative to eliminate FLX and to decrease residual toxicity from wastewater generated in pharmaceutical formulation facilities, although further investigation is needed for correlating the FLX degradation mechanism with the toxicity results. PMID:26961524

  1. Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system.

    PubMed

    Lenzi, Juliana; Rodrigues, Andre Felipe; Rós, Adriana de Sousa; de Castro, Amanda Blanski; de Castro, Bianca Blanski; de Lima, Daniela Delwing; Magro, Débora Delwing Dal; Zeni, Ana Lúcia Bertarello

    2015-12-01

    Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation.

  2. Association of FKBP51 with Priming of Autophagy Pathways and Mediation of Antidepressant Treatment Response: Evidence in Cells, Mice, and Humans

    PubMed Central

    Zschocke, Jürgen; Stepan, Jens; Hafner, Kathrin; Zellner, Andreas; Kirmeier, Thomas; Kollmannsberger, Lorenz; Wagner, Klaus V.; Dedic, Nina; Balsevich, Georgia; Deussing, Jan M.; Kloiber, Stefan; Lucae, Susanne; Holsboer, Florian; Eder, Matthias; Uhr, Manfred; Ising, Marcus; Schmidt, Mathias V.; Rein, Theo

    2014-01-01

    Background FK506 binding protein 51 (FKBP51) is an Hsp90 co-chaperone and regulator of the glucocorticoid receptor, and consequently of stress physiology. Clinical studies suggest a genetic link between FKBP51 and antidepressant response in mood disorders; however, the underlying mechanisms remain elusive. The objective of this study was to elucidate the role of FKBP51 in the actions of antidepressants, with a particular focus on pathways of autophagy. Methods and Findings Established cell lines, primary neural cells, human blood cells of healthy individuals and patients with depression, and mice were treated with antidepressants. Mice were tested for several neuroendocrine and behavioral parameters. Protein interactions and autophagic pathway activity were mainly evaluated by co-immunoprecipitation and Western blots. We first show that the effects of acute antidepressant treatment on behavior are abolished in FKBP51 knockout (51KO) mice. Autophagic markers, such as the autophagy initiator Beclin1, were increased following acute antidepressant treatment in brains from wild-type, but not 51KO, animals. FKBP51 binds to Beclin1, changes decisive protein interactions and phosphorylation of Beclin1, and triggers autophagic pathways. Antidepressants and FKBP51 exhibited synergistic effects on these pathways. Using chronic social defeat as a depression-relevant stress model in combination with chronic paroxetine (PAR) treatment revealed that the stress response, as well as the effects of antidepressants on behavior and autophagic markers, depends on FKBP51. In human blood cells of healthy individuals, FKBP51 levels correlated with the potential of antidepressants to induce autophagic pathways. Importantly, the clinical antidepressant response of patients with depression (n = 51) could be predicted by the antidepressant response of autophagic markers in patient-derived peripheral blood lymphocytes cultivated and treated ex vivo (Beclin1/amitriptyline: r = 0.572, p

  3. 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

  4. 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

  5. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    PubMed Central

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  6. Medical treatment of acute pancreatitis.

    PubMed

    Mayerle, Julia; Simon, Peter; Lerch, Markus M

    2004-12-01

    Eighty percent of all cases of acute pancreatitis are linked etiologically to gallstone disease or caused by immoderate alcohol consumption. No specific causal treatment for acute pancreatitis exists. Early prognostic factors that indicate severe disease are three or more signs on organ failure scores according to Ranson, Imrie, or Acute Physiology and Chronic Health Evaluation (APACHE) 11, extrapancreatic complications of the disease, or the detection of pancreatic necrosis on CT scans. Elevated CRP levels above 130 mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Moreover, relief of often severe visceral pain is a high priority. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis, or other infectious complications. Enteral nutrition has no adverse effect compared with parenteral nutrition during the course of acute pancreatitis, and is probably beneficial in regard to outcome.

  7. Subchronic alpha-linolenic acid treatment enhances brain plasticity and exerts an antidepressant effect: a versatile potential therapy for stroke.

    PubMed

    Blondeau, Nicolas; Nguemeni, Carine; Debruyne, David N; Piens, Marie; Wu, Xuan; Pan, Hongna; Hu, XianZhang; Gandin, Carine; Lipsky, Robert H; Plumier, Jean-Christophe; Marini, Ann M; Heurteaux, Catherine

    2009-11-01

    Omega-3 polyunsaturated fatty acids are known to have therapeutic potential in several neurological and psychiatric disorders. However, the molecular mechanisms of action underlying these effects are not well elucidated. We previously showed that alpha-linolenic acid (ALA) reduced ischemic brain damage after a single treatment. To follow-up this finding, we investigated whether subchronic ALA treatment promoted neuronal plasticity. Three sequential injections with a neuroprotective dose of ALA increased neurogenesis and expression of key proteins involved in synaptic functions, namely, synaptophysin-1, VAMP-2, and SNAP-25, as well as proteins supporting glutamatergic neurotransmission, namely, V-GLUT1 and V-GLUT2. These effects were correlated with an increase in brain-derived neurotrophic factor (BDNF) protein levels, both in vitro using neural stem cells and hippocampal cultures and in vivo, after subchronic ALA treatment. Given that BDNF has antidepressant activity, this led us to test whether subchronic ALA treatment could produce antidepressant-like behavior. ALA-treated mice had significantly reduced measures of depressive-like behavior compared with vehicle-treated animals, suggesting another aspect of ALA treatment that could stimulate functional stroke recovery by potentially combining acute neuroprotection with long-term repair/compensatory plasticity. Indeed, three sequential injections of ALA enhanced protection, either as a pretreatment, wherein it reduced post-ischemic infarct volume 24 h after a 1-hour occlusion of the middle cerebral artery or as post-treatment therapy, wherein it augmented animal survival rates by threefold 10 days after ischemia. PMID:19641487

  8. Impact of social status and antidepressant treatment on neurogenesis in the baboon hippocampus.

    PubMed

    Wu, Melody V; Shamy, Jul Lea; Bedi, Gillinder; Choi, Chien-Wen J; Wall, Melanie M; Arango, Victoria; Boldrini, Maura; Foltin, Richard W; Hen, René

    2014-07-01

    Adult hippocampal neurogenesis is critically implicated in rodent models of stress and anxiety as well as behavioral effects of antidepressants. Whereas similar factors such as psychiatric disorder and antidepressant administration are correlated with hippocampal volume in humans, the relationship between these factors and adult neurogenesis is less well understood. To better bridge the gap between rodent and human physiology, we examined the numbers of proliferating neural precursors and immature cells in the hippocampal dentate gyrus (DG) as well as in vivo magnetic resonance imaging (MRI)-estimated whole hippocampal volume in eight socially dominant- or subordinate-like (SL) baboons administered the antidepressant fluoxetine or vehicle. SL baboons had lower numbers of proliferating cells and immature neurons than socially dominant-like baboons. Fluoxetine treatment was associated with a larger whole hippocampal volume but surprisingly resulted in lower numbers of immature neurons. These findings are the first to indicate that adult neurogenesis in the baboon hippocampal DG may be functionally relevant in the context of social stress and mechanisms of antidepressant action.

  9. Managing antidepressant treatment in pregnancy and puerperium. Careful with that axe, Eugene.

    PubMed

    Gentile, Salvatore

    2015-07-01

    Until 2005, selective serotonin reuptake inhibitors (SSRIs), the class of antidepressants most frequently used in clinical practice, had been deemed devoid of any teratogenic effects. However, in recent years several concerns have been raised about their reproductive safety, including: disturbed fetal development, increased rates of congenital anomalies, increased risks of neonatal complications, neuro-motor delay and even autism. Specific concerns are also arising about the safety of SSRIs for infants breastfed by mothers who take such medications in puerperium. Such considerations have led to the 'bad reproductive reputation' of SSRIs, whose utilization during pregnancy and breastfeeding is deemed incautious. Specific reproductive problems also involve tricyclic antidepressants, especially clomipramine. Thus, any conclusion about what antidepressant should be considered the safest during pregnancy must be stated and read with great caution. However, the risks associated with pharmacological treatment must be balanced with the effects of untreated antenatal maternal depression on the mother-fetus dyad, which are likely to be devastating. During puerperium, it is mandatory to weigh the risks to the infant of antidepressant exposure through breast milk against the disadvantage of not receiving mother's milk and being exposed to a relapse of maternal mood symptoms (which may also have tragic consequences for the patient). PMID:25882518

  10. PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder.

    PubMed

    Schuhmacher, Anna; Mössner, Rainald; Höfels, Susanne; Pfeiffer, Ute; Guttenthaler, Vera; Wagner, Michael; Schwab, Sibylle G; Maier, Wolfgang; Zobel, Astrid

    2011-03-01

    Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity. We investigated the influence of the coding variant rs2522833 in the PCLO gene on treatment response in 205 in-patients with unipolar depression. Treatment response was measured (1) at the level of psychopathology using the Hamilton Depression Rating Scale (HAMD) and (2) with the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which is a refined tool for showing dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, a neurobiological finding in depression. While we did not find an association between variation in PCLO and HAMD scores, HPA dysregulation was less pronounced in carriers of the AA genotype than in carriers of one or two C alleles. HPA activity of individuals with the AA genotype only marginally changed during 4-wk antidepressant treatment, whereas C allele carriers showed a higher hormonal secretion at admission than carriers of the AA genotype but lower responsivity to the Dex/CRH challenge after 4 wk. Our results point to a moderating role of PCLO SNP rs2522833 on HPA regulation during antidepressant treatment, which may represent a neurobiological feature of stability of clinical response.

  11. Are there gender differences in the temperature profile of mice after acute antidepressant administration and exposure to two animal models of depression?

    PubMed

    David, D J; Nic Dhonnchadha, B A; Jolliet, P; Hascoët, M; Bourin, M

    2001-03-15

    Numerous studies have reported gender differences in the rates of depression in humans, but few behavioural observations of antidepressant drug effects have been investigated in female mice. The forced swimming test (FST) is widely used as a predictor of antidepressant activity in rodents, as is the tail suspension test (TST), where immobility is objectively measured and in this last test, no hypothermia is induced by immersion in cold water. The present study investigated gender differences in the temperature profile of mice after acute antidepressant administration (imipramine and paroxetine) and exposure to two animal models of depression. Imipramine and paroxetine were active at 32 mg/kg in male mice in the FST, whereas they were active at 8, 16 and 32 mg/kg in female mice. In the TST, for both antidepressants immobility duration was reduced at a dose of 16 and 32 mg/kg in male mice and at 32 mg/kg in female mice. No significant difference was observed between male and female mice for immobility duration. Imipramine administration, but not paroxetine, decreased the temperature at the higher dose (32 mg/kg) in male and female mice in the FST. The body temperature was reduced in male and female mice for all treatment groups after FST challenge. Imipramine (16 and 32 mg/kg in male and 32 mg/kg in female mice), paroxetine (4, 16 and 32 mg/kg in male and 4 to 32 mg/kg in female mice) attenuated the reduction in temperature due to the FST. In the TST, imipramine tends to decrease the temperature in male and female mice, even though only imipramine at a dose of 32 mg/kg in female mice significantly decreases the temperature. Paroxetine had no effect on temperature. The TST enhanced the body temperature in male and female mice. In mice, there was no difference between the sexes after imipramine or paroxetine administration in the FST and TST. Both tests can be used to predict the activity of antidepressants as the decrease or enhancement of temperature is not

  12. A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression

    PubMed Central

    Pimontel, Monique A.; Rindskopf, David; Rutherford, Bret R.; Brown, Patrick J.; Roose, Steven P.; Sneed, Joel R.

    2015-01-01

    Objective Depressed older adults with executive dysfunction (ED) may respond poorly to antidepressant treatment. ED is a multifaceted construct and different studies have measured different aspects of ED, making it unclear which aspects predict poor response. Meta-analytic methods were used to determine whether ED predicts poor antidepressant treatment response in late-life depression and to determine which domains of executive functioning are responsible for this relationship. Methods A Medline search was conducted to identify regimented treatment trials contrasting executive functioning between elderly responders and nonresponders; only regimented treatment trials for depressed outpatients aged 50 and older were included. Following the most recent PRISMA guidelines, 25 measures of executive functioning were extracted from eight studies. Six domains were identified: cognitive flexibility, planning and organization, response inhibition, selective attention, verbal fluency, and the Dementia Rating Scale Initiation/Perseveration composite score (DRS I/P). Hedge’s g was calculated for each measure of executive functioning. A three-level Bayesian hierarchical linear model (HLM) was used to estimate effect sizes for each domain of executive functioning. Results The effect of planning and organization was significantly different from zero (Bayesian HLM estimate of domain effect size: 0.91; 95% CI: 0.32–1.58), whereas cognitive flexibility, response inhibition, selective attention, verbal fluency, and the DRS I/P composite score were not. Conclusion The domain of planning and organization is meaningfully associated with poor antidepressant treatment response in late-life depression. These findings suggest that therapies that focus on planning and organization may provide effective augmentation strategies for antidepressant nonresponders with late-life depression. PMID:26282222

  13. Structural Imaging in Late Life Depression: Association with Mood and Cognitive Responses to Antidepressant Treatment

    PubMed Central

    Marano, Christopher M.; Workman, Clifford I.; Lyman, Christopher H.; Munro, Cynthia A.; Kraut, Michael A.; Smith, Gwenn S.

    2014-01-01

    Objectives Recent positron emission tomography studies of cerebral glucose metabolism have identified the functional neural circuitry associated with mood and cognitive responses to antidepressant treatment in late life depression (LLD). The structural alterations in these networks are not well understood. The present study used magnetic resonance (MR) imaging and voxel-based morphometry (VBM) to evaluate the association between grey matter volumes and changes in mood symptoms and cognitive function with treatment with the antidepressant citalopram. Design Open label trial with baseline brain MR scan. Mood and cognitive assessments performed at baseline and during citalopram treatment. Setting Outpatient clinics of an academic medical center. Participants 17 previously unmedicated patients age 55 or older with a major depressive episode and 17 non-depressed comparison subjects. Intervention 12 week trial of flexibly dosed citalopram. Measurements Grey matter volumes, Hamilton Depression Rating Scale, California Verbal Learning Test, Delis–Kaplan Executive Function System™. Results In LLD, higher grey matter volumes in the cingulate gyrus, superior and middle frontal gyri, middle temporal gyrus and precuneus was associated with greater mood improvement. Higher grey matter volumes in primarily frontal areas were associated with greater improvement in verbal memory and verbal fluency performance. Conclusions Associations with antidepressant induced improvements in mood and cognition were observed in several brain regions previously correlated with normalization of glucose metabolism after citalopram treatment in LLD. Future studies will investigate molecular mechanisms underlying these associations (e.g. beta-amyloid, inflammation, glutamate). PMID:24238925

  14. Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis.

    PubMed

    Song, Guo-Min; Tian, Xu; Shuai, Ting; Yi, Li-Juan; Zeng, Zi; Liu, Shuang; Zhou, Jian-Guo; Wang, Yan

    2015-07-01

    Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta-analysis.Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biomediccal Literatures Database), and CNKI (China National Knowledge Infrastructure) were searched for relevant studies through November 21, 2014. Literature was screened, data were extracted and methodological quality of the eligible trial was assessed by 2 independent reviewers accordingly. Then, head-to-head and indirect comparison meta-analyses were carried out.A total of 17 studies which including 13 studies regarding ECT plus antidepressant versus antidepressant alone and 4 studies concerning ECT versus antidepressant alone containing a total of 1098 patients were incorporated into this meta-analysis. The head-to-head comparison suggested that response rate can be improved in the ECT plus antidepressant (RR, 1.82; 95% CI, 1.55-2.14) and ECT alone group (RR, 2.24, 95% CI, 1.51-3.33) compared with antidepressant alone, respectively; adverse complications including memory deterioration and somatization were not significantly increased except incidence of memory deterioration in ECT plus antidepressant in the 4th weeks after treatment (RR, 0.09, 95% CI, 0.02-0.49). Indirect comparison meta-analysis showed that no significant differences were detected in response rate and memory deterioration between ECT plus antidepressant and ECT alone. However, ECT plus antidepressant increased the incidence of memory deterioration relative to ECT alone.With present evidence, the regime of ECT plus antidepressant should not be preferentially recommended to treat the patients with TRD relative to ECT

  15. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis.

    PubMed Central

    Anderson, I. M.; Tomenson, B. M.

    1995-01-01

    OBJECTIVE--To assess treatment discontinuation rates with selective serotonin reuptake inhibitors compared with tricyclic antidepressants. DESIGN--Meta-analysis of 62 randomised controlled trials. SUBJECTS--6029 patients with major unipolar depression. MAIN OUTCOME MEASURES--Pooled risk ratios for drop out rates with respect to all cases of discontinuation and those due to side effects and treatment failure. RESULTS--The total discontinuation rate was 10% lower with selective serotonin reuptake inhibitors than with tricyclic antidepressants (risk ratio 0.90; 95% confidence interval 0.84 to 0.97) and the drop out rate due to side effects was 25% lower (risk ratio 0.75; 0.66 to 0.84). There was no significant difference between drug classes in the drop out rates for treatment failure. The risk ratios for drop out did not differ significantly between individual selective serotonin reuptake inhibitors. CONCLUSIONS--Selective serotonin reuptake inhibitors are better tolerated than tricyclic antidepressants as measured by total numbers of drop outs. The definite advantage to selective serotonin reuptake inhibitors is explained by fewer drop outs due to side effects. The overall difference, however, is comparatively small and may not be clinically relevant. Analyses of cost effectiveness should not overestimate the advantage to selective serotonin reuptake inhibitors. PMID:7613276

  16. Acute Migraine Treatment in Adults.

    PubMed

    Becker, Werner J

    2015-06-01

    There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID-triptan combinations, dihydroergotamine, non-opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti-emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence-based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication

  17. Adherence to antidepressant treatment: what the doctor thinks and what the patient says.

    PubMed

    Loayza, N; Crettol, S; Riquier, F; Eap, C B

    2012-07-01

    Adherence to antidepressant treatment has been shown to range from 30 to 70%. The aim of this study was to compare the patient's self-report of adherence with the doctors' estimation of adherence and therapeutic alliance in 104 outpatients with mood and/or anxiety disorder treated with antidepressants. The adherence scores estimated by the patients and the doctors were significantly different, the doctors underestimating adherence in 29% of cases and overestimating it in 31% of cases compared to the patients' evaluation. Adherence measured by drug plasma concentration, despite being higher than expected from previously published reports, was in line with the patients' self-reported score but not the doctors' estimation. Finally, the patients' and the doctors' Helping Alliance scores were not related to adherence self-report.

  18. Identification of genes regulated by chronic psychosocial stress and antidepressant treatment in the hippocampus.

    PubMed

    Alfonso, Julieta; Pollevick, Guido D; Van Der Hart, Marieke G; Flügge, Gabriele; Fuchs, Eberhard; Frasch, Alberto C C

    2004-02-01

    Analysis of differentially expressed genes in the brain is a promising tool for elucidating pathological mechanisms that lead to central nervous disorders. Stress is known to be involved in the development of psychopathologies such as depression. In the present study, we searched for differentially expressed genes in the hippocampal formation after chronic psychosocial stress and after treatment with the antidepressant clomipramine. Experiments were conducted in male tree shrews, a valid psychosocial stress model in which antidepressant drugs prevent diverse effects of stress. Because many effects of stress have been attributed to the stress-induced elevation in glucocorticoids, we screened two subtractive hippocampal cDNA libraries generated from RNA of chronic cortisol-treated animals. Using real-time PCR to measure mRNA amounts, we identified five sequences whose expression levels differed between stressed animals and controls. Transcript levels of four of them, nerve growth factor (NGF), membrane glycoprotein 6a (M6a), CDC-like kinase 1 (CLK-1) and G-protein alpha q (GNAQ) were reduced by chronic psychosocial stress. Reduced amounts of these genes, which are all related to processes of cell differentiation, is in agreement with previous findings showing a retraction of dendrites and an impairment of neurogenesis in the hippocampal formation after chronic stress. An additional expressed sequence that was also regulated by stress could not be assigned to any known gene. Treatment with the antidepressant clomipramine prevented stress effects on expression of M6a, CLK-1, GNAQ and the novel sequence, but showed no effect on NGF stress-induced down-regulation. These findings support the concept that depressive disorders are accompanied by processes of neuronal dedifferentiation, at least in the hippocampal formation, and that antidepressants prevent these processes. PMID:14984416

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

    PubMed Central

    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

  20. Pretreatment anterior cingulate activity predicts antidepressant treatment response in major depressive episodes.

    PubMed

    Rentzsch, Johannes; Adli, Mazda; Wiethoff, Katja; Gómez-Carrillo de Castro, Ana; Gallinat, Jürgen

    2014-04-01

    Major depressive disorder leads to substantial individual and socioeconomic costs. Despite the ongoing efforts to improve the treatment for this condition, a trial-and-error approach until an individually effective treatment is established still dominates clinical practice. Searching for clinically useful treatment response predictors is one of the most promising strategies to change this quandary therapeutic situation. This study evaluated the predictive value of a biological and a clinical predictor, as well as a combination of both. Pretreatment EEGs of 31 patients with a major depressive episode were analyzed with neuroelectric brain imaging technique to assess cerebral oscillations related to treatment response. Early improvement of symptoms served as a clinical predictor. Treatment response was assessed after 4 weeks of antidepressant treatment. Responders showed more slow-frequency power in the right anterior cingulate cortex compared to non-responders. Slow-frequency power in this region was found to predict response with good sensitivity (82 %) and specificity (100 %), while early improvement showed lower accuracy (73 % sensitivity and 65 % specificity). Combining both parameters did not further improve predictive accuracy. Pretreatment activity within the anterior cingulate cortex is related to antidepressive treatment response. Our results support the search for biological treatment response predictors using electric brain activity. This technique is advantageous due to its low individual and socioeconomic burden. The benefits of combining both, a clinically and a biologically based predictor, should be further evaluated using larger sample sizes.

  1. Switching and stopping antidepressants.

    PubMed

    Keks, Nicholas; Hope, Judy; Keogh, Simone

    2016-06-01

    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

  2. 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

  3. 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

  4. Obesity and Its Potential Effects on Antidepressant Treatment Outcomes in Patients with Depressive Disorders: A Literature Review.

    PubMed

    Woo, Young Sup; Seo, Hye-Jin; McIntyre, Roger S; Bahk, Won-Myong

    2016-01-12

    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.

  5. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  6. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  7. Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice.

    PubMed

    Crupi, Rosalia; Mazzon, Emanuela; Marino, Angela; La Spada, Giuseppina; Bramanti, Placido; Cuzzocrea, Salvatore; Spina, Edoardo

    2010-09-01

    Melatonin, involved in circadian cycle, provides protective effects on neuronal cells and acts as antidepressant by restoration of corticosterone levels. A mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone treatment, has been used to evaluate behavior and adult hippocampal neurogenesis in mice and their possible modulation under melatonin. With this aim, CD1 mice were subjected to 7 wk of corticosterone administration, and then behavioral tests as novelty-suppressed feeding, open field and a forced swim test were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by 5-bromo-2'-deoxyuridine and doublecortin immunohistochemistry techniques, and stereological procedure was used to quantify labeled cells. Golgi-impregnated method was used to evaluate the changes of dendritic spines in DG neurons. A new therapeutic approach with antidepressant-like substances (3 wk) such as melatonin (8 mg/kg) was employed to possibly modulate neural development in the adult hippocampus and the behavioral changes. The depressive-like state caused by chronic corticosterone treatment was reversed by exogenous administration of melatonin; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment (cort- 83.7 +/- 20.3 versus cort+ 60.5 +/- 18.2; P < 0.05), whereas long-term treatment with melatonin prevented the corticosterone-induced reduction in hippocampal cell proliferation (cort- 60.5 +/- 18.2 versus mel 133.4 +/- 26.9; P < 0.05). Corticosterone-treated mice exhibited a reduced spine density, which was ameliorated by melatonin administration. These findings suggest a strong correspondence between behavior and neurogenesis, strengthening the hypothesis that neurogenesis contributes to the effects of melatonin as an antidepressant. PMID:20536684

  8. Improvement of Glycemic Control in Insulin-Dependent Diabetics with Depression by Concomitant Treatment with Antidepressants

    PubMed Central

    Radojkovic, Jana; Sikanic, Natasa; Bukumiric, Zoran; Tadic, Marijana; Kostic, Nada; Babic, Rade

    2016-01-01

    Background It is still disputable whether negative effects of comorbid depression in diabetics can be diminished by successful treatment of depression. The primary aim of this study was to assess whether addition of antidepressants to existing insulin treatment would further improve glycemic control in these patients. A secondary objective was to assess whether such treatment impairs their lipid and inflammatory status. Material/Methods Total of 192 patients with poorly controlled diabetes (defined as HbA1c ≥8%) in the absence of any uncontrolled medical condition entered the 6-month run-in phase with optimization of diabetic therapy. Depression status was screened at the end of this phase by BDI-II depression testing. Patients with BDI-II ≥14 and psychiatric confirmation of depression (58 patients) entered the 6-month interventional phase with SSRI class antidepressants. Results Fifty patients completed the study. During the run-in phase, HbA1c dropped from 10.0±1.8% to 8.5±1.2% (p<0.001), and during the interventional phase it dropped from 8.5±1.2% to 7.7±0.7% (p<0.001). BDI-II scores improved significantly from 30.4±13.2 to 23.5±11.0 (p=0.02) during the interventional phase. A positive linear correlation between improvement in depression scale and improvement in glycemic control was observed (R2=0.139, p=0.008). Lipid profile and inflammatory status did not change significantly during the interventional phase. Conclusions Patients with poorly controlled diabetes and comorbid depression might benefit from screening and treatment of depression with SSRI antidepressants by achieving an incremental effect on glycoregulation. This therapy did not have any adverse effects on lipid profile or inflammatory status. PMID:27329213

  9. Improvement of Glycemic Control in Insulin-Dependent Diabetics with Depression by Concomitant Treatment with Antidepressants.

    PubMed

    Radojkovic, Jana; Sikanic, Natasa; Bukumiric, Zoran; Tadic, Marijana; Kostic, Nada; Babic, Rade

    2016-01-01

    BACKGROUND It is still disputable whether negative effects of comorbid depression in diabetics can be diminished by successful treatment of depression. The primary aim of this study was to assess whether addition of antidepressants to existing insulin treatment would further improve glycemic control in these patients. A secondary objective was to assess whether such treatment impairs their lipid and inflammatory status. MATERIAL AND METHODS Total of 192 patients with poorly controlled diabetes (defined as HbA1c ≥8%) in the absence of any uncontrolled medical condition entered the 6-month run-in phase with optimization of diabetic therapy. Depression status was screened at the end of this phase by BDI-II depression testing. Patients with BDI-II ≥14 and psychiatric confirmation of depression (58 patients) entered the 6-month interventional phase with SSRI class antidepressants. RESULTS Fifty patients completed the study. During the run-in phase, HbA1c dropped from 10.0±1.8% to 8.5±1.2% (p<0.001), and during the interventional phase it dropped from 8.5±1.2% to 7.7±0.7% (p<0.001). BDI-II scores improved significantly from 30.4±13.2 to 23.5±11.0 (p=0.02) during the interventional phase. A positive linear correlation between improvement in depression scale and improvement in glycemic control was observed (R²=0.139, p=0.008). Lipid profile and inflammatory status did not change significantly during the interventional phase. CONCLUSIONS Patients with poorly controlled diabetes and comorbid depression might benefit from screening and treatment of depression with SSRI antidepressants by achieving an incremental effect on glycoregulation. This therapy did not have any adverse effects on lipid profile or inflammatory status. PMID:27329213

  10. Acute treatment of migraine headaches.

    PubMed

    Taylor, Frederick R

    2010-04-01

    Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes. PMID:20352584

  11. Mitochondrial plasticity of the hippocampus in a genetic rat model of depression after antidepressant treatment.

    PubMed

    Chen, Fenghua; Wegener, Gregers; Madsen, Torsten M; Nyengaard, Jens R

    2013-03-01

    Depressive disorders and the treatment thereof have been associated with a number of neuroplastic events, such as neurogenesis and synaptic remodeling in discrete areas of the brain. The associations of these events in changes regarding the energy supply have not been investigated. Here, we investigated the changes in mitochondrial plasticity and its correlation to morphological alterations of neuroplasticity in the hippocampus, both associated with a depressive phenotype, and after treatment, with antidepressant imipramine. Design-based stereological methods were used to estimate the number and volume of mitochondria in CA1 of the hippocampus in two different strains of rats, the Sprague-Dawley (SD) and Flinders rats, which display a genetic susceptibility to depressive behavior, the Flinders-sensitive line (FSL) and their corresponding controls, the Flinders-resistant line (FRL). Results showed a significantly reduced number of mitochondria in CA1, which was significantly smaller in the untreated FSL saline group compared to the FRL group. However, the mean volume of mitochondria was significantly larger in the FSL saline group compared to the FRL saline group. Following treatment, the FSL imipramine group showed a significant increase in the number of mitochondria compared to the FSL saline group. Treatment with imipramine in the SD rats did not induce significant differences in the number of mitochondria. Our results indicate that depression may be related to impairments of mitochondrial plasticity in the hippocampus and antidepressant treatment may counteract with the structural impairments. Moreover, the changes in mitochondrial morphology and number are a consistent feature of neuroplasticity.

  12. Increased neuroplasticity and hippocampal microglia activation in a mice model of rapid antidepressant treatment.

    PubMed

    Muzio, Luca; Brambilla, Valentina; Calcaterra, Lorenza; D'Adamo, Patrizia; Martino, Gianvito; Benedetti, Francesco

    2016-09-15

    The search for biomarkers of antidepressant effects focused on pathways regulating synaptic plasticity, and on activated inflammatory markers. Repeated Sleep Deprivation (SD) provides a model treatment to reverse-translate antidepressant effects from in vivo clinical psychiatry to model organisms. We studied the effects of repeated SD alone (ASD) or combined with exercise on a slow spinning wheel (SSW), in 116 C57BL/6J male mice divided in three groups (ASD, SSW, untreated). Forced Swimming Test (FST) was used to detect antidepressant-like effects. Unbiased evaluation of the transcriptional responses were obtained in the hippocampus by Illumina Bead Chip Array system, then confirmed with real time PCR. Spine densities in granular neurons of the dentate gyrus (DG) were assayed by standard Golgi staining. Activation of Microglial/Macrophages cells was evaluated by immunufluorescence analysis for Iba1. Rates of cell proliferation was estimated pulsing mice with the S-phase tracer 5-Iodo-2'-deoxyuridine (IdU). All SD procedures caused a decreasing of floating time at FST, and increased expression of the immediate early gene Arc/Arg3.1. In addition, SSW also increased expression of the Microglia/Macrophages genes Iba-1 and chemokine receptors Cx3cR1 and CxcR4, of the canonical Wnt signaling gene Wnt7a, and of dendritic spines in CA4 neurons of the DG. SSW up-regulated both the number of Iba1+ cells and rates of cell proliferation in the subgranular region of the DG. The antidepressant-like effects of SD dissociated both, from hippocampal neuroplasticity in the DG (not occurring after ASD), and from microglial activation (not preventing behavioral response when occurring). The increase in dendritic spine density in the DG after SD and exercise was associated with an up-regulation of Wnt 7a, and with activation of the innate immune system of the brain. Increased Arc/Arg3.1 suggests however increased neuroplasticity, which could be common to all fast-acting antidepressants

  13. Escitalopram versus other antidepressive agents for depression

    PubMed Central

    Cipriani, Andrea; Santilli, Claudio; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; McGuire, Hugh; Churchill, Rachel; Barbui, Corrado

    2014-01-01

    Background Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs remain the mainstay of treatment in primary and secondary care settings. During the last 20 years, antidepressant prescribing has risen dramatically in western countries, mainly because of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants, which have progressively become the most commonly prescribed antidepressants. Escitalopram is the pure S-enantiomer of the racemic citalopram. Objectives To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics, other SSRIs, heterocyclics and newer agents in the acute-phase treatment of major depression. Search methods Electronic databases were searched up to July 2008. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. Selection criteria All randomised controlled trials comparing escitalopram against any other antidepressant (including non-conventional agents such as hypericum) for patients with major depressive disorder (regardless of the diagnostic criteria used). Data collection and analysis Data were entered by two review authors (double data entry). Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI) using the random effects model. Main results Fourteen trials compared escitalopram with another SSRI and eight compared escitalopram with a newer antidepressive agent (venlafaxine, bupropion and duloxetine). Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (OR 0.67, 95% CI 0.50 to 0.87). Escitalopram was also more effective than citalopram in terms of remission (OR

  14. FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties

    PubMed Central

    Wolfe, Sarah A.; Workman, Emily R.; Heaney, Chelcie F.; Niere, Farr; Namjoshi, Sanjeev; Cacheaux, Luisa P.; Farris, Sean P.; Drew, Michael R.; Zemelman, Boris V.; Harris, R. Adron; Raab-Graham, Kimberly F.

    2016-01-01

    Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters γ-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium. Furthermore, new GABABRs are synthesized in response to ethanol treatment, requiring fragile-X mental retardation protein (FMRP). Ethanol-dependent changes in GABABR expression, dendritic signalling, and antidepressant efficacy are absent in Fmr1-knockout (KO) mice. These findings indicate that FMRP is an important regulator of protein synthesis following alcohol exposure, providing a molecular basis for the antidepressant efficacy of acute ethanol exposure. PMID:27666021

  15. 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

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

    PubMed Central

    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

  17. Lack of association of acute phase response proteins with hormone levels and antidepressant medication in perimenopausal depression

    PubMed Central

    2014-01-01

    Background Major depression is associated with higher plasma levels of positive acute-phase proteins, as well as with lower plasma levels of negative acute-phase proteins. The aim of this study is to examine the levels of acute-phase response proteins and whether these levels are influenced by reproductive hormones and antidepressant medication in the perimenopausal depression. Methods Sixty-five women (age range: 40–58 years old) participated in this study. All women were in the perimenopausal phase. The diagnosis of depression was made through a psychiatric interview and with the aid of Hamilton Depression Rating Scale 17 (HAM-D 17). The acute-phase response proteins, such as haptoglobin (HP), transferrine (TRf), α1-antitrypsin, complement protein 3 (C3), complement protein 4 (C4) and C-reactive protein (CRP) and the reproductive hormones, for example follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), were analyzed using standard laboratory methods. Pearson’s correlations were applied to evaluate the relationship between acute-phase proteins and hormones. Results Perimenopausal women were divided into three groups. The first group consisted of normal controls, the second one involved depressed perimenopausal women, who were taking selective serotonin reuptake inhibitors (SSRIs), and the third one included depressed women that were not treated with SSRIs. Depressed women in perimenopause, when being compared to non-depressed women, did not differ as to serum levels of acute-phase proteins. There was a positive correlation between HP and E2 in depressed perimenopausal women, who were not taking SSRIs. Conclusions The lack of association between acute-phase proteins and depressive mood mentioned in this study does not support previous findings in patients with major depression. This negative finding in perimenopausal depression indicates either the absence or a more complex nature of the interactions between acute-phase proteins

  18. Lithium and Valproate Levels Do Not Correlate with Ketamine's Antidepressant Efficacy in Treatment-Resistant Bipolar Depression.

    PubMed

    Xu, Annie J; Niciu, Mark J; Lundin, Nancy B; Luckenbaugh, David A; Ionescu, Dawn F; Richards, Erica M; Vande Voort, Jennifer L; Ballard, Elizabeth D; Brutsche, Nancy E; Machado-Vieira, Rodrigo; Zarate, Carlos A

    2015-01-01

    Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine's antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine's antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n = 23, 0.79 ± 0.15 mEq/L) or valproate (n = 13, 79.6 ± 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure-the Montgomery-Åsberg Depression Rating Scale (MADRS)-was assessed before infusion and at numerous postinfusion time points. Both lithium (F 1,118 = 152.08, p < 0.001, and d = 2.27) and valproate (F 1,128 = 20.12, p < 0.001, and d = 0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F 1,28 = 2.51, p = 0.12, and d = 0.60). Serum lithium and valproate levels did not correlate with ketamine's antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithium may not potentiate ketamine's antidepressant efficacy in treatment-resistant bipolar depression.

  19. A Randomized, Placebo-Controlled Pilot Study of Quetiapine-XR Monotherapy or Adjunctive Therapy to Antidepressant in Acute Major Depressive Disorder with Current Generalized Anxiety Disorder

    PubMed Central

    Li, Ranran; Wu, Renrong; Chen, Jun; Kemp, David E.; Ren, Ming; Conroy, Carla; Chan, Philip; Serrano, Mary Beth; Ganocy, Stephen J.; Calabrese, Joseph R.; Gao, Keming

    2016-01-01

    Objectives To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD). Methods The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures. Results Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue. Conclusions In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings.

  20. [The dynamics of anxious depression under the treatment with antidepressants with different mechanisms of action].

    PubMed

    Maksimova, N M; Vertogradova, O P

    2012-01-01

    Peculiarities of the dynamics of anxious depression under the treatment with selective serotonergic antidepressants with different mechanisms of action on the serotonin reuptake were investigated. It was examined 61 patients with anxious depression (ICD-10 F32.1, F33.1, F34.1) treated with zoloft (sertraline) or coaxil (tianeptine) as a monotherapy. The following methods were used: clinical-psychopathological, psychometric (Hamilton Rating Scales for Depression and Anxiety, the Sheehan Patient-Related Anxiety Scale) and statistical analysis. The comparative investigation has shown that both zoloft and coaxil are practically equally effective in the treatment of anxious depression with some peculiarities in the dynamics of clinical parameters. PMID:23257755

  1. Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus.

    PubMed

    Alboni, Silvia; Benatti, Cristina; Montanari, Claudia; Tascedda, Fabio; Brunello, Nicoletta

    2013-12-01

    To gain insight into the possible immune targets of antidepressant, we evaluated the expression of several inflammatory mediators in the hypothalamus of rats chronically (28 days) treated with the serotonin selective reuptake inhibitor fluoxetine (5mg/kg, i.p.) or the tricyclic compound imipramine (15 mg/kg, i.p.). We focused our attention on the hypothalamus as it plays a key role in determining many of the somatic symptoms experienced by depressed patients. This brain region, critical also for expression of motivated behaviours, participates in the control of the hypothalamic-pituitary-adrenal axis activity and in stress response as well as coordinates physiological functions such as sleep and food intake that have been found altered in a high percentage of depressed patients. Notably, hypothalamus is a key structure for brain cytokine expression and function as it integrates signals from the neuro, immune, endocrine systems. By means of quantitative Real Time PCR experiments we demonstrated that a chronic treatment with either fluoxetine or imipramine resulted in a reduction of IL-6 and IFN-γ mRNAs and increased IL-4 mRNA expression in the rat hypothalamus. Moreover, we demonstrated that hypothalamic expression of members of IL-18 system was differentially affected by chronic antidepressant treatments. Chronically administered fluoxetine decreased IL-8 and CX3CL1 hypothalamic expression, while a chronic treatment with imipramine decreased p11 mRNA. Our data suggest that a shift in the balance of the inflammation toward an anti-inflammatory state in the hypothalamus may represent a common mechanism of action of both the chronic treatments with fluoxetine and imipramine.

  2. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression.

    PubMed

    Thomas, Samantha J; Shin, Mirae; McInnis, Melvin G; Bostwick, Jolene R

    2015-04-01

    Treatment-resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose for an adequate duration fail to respond. Further, approximately half of adults with major depressive disorder fail to achieve sustained remission despite various medication trials. The utilization of monoamine oxidase inhibitors (MAOIs) for the treatment of depression in clinical practice today is low due to their widely known adverse effects, some of which may be life threatening, and the risk for dietary and drug interactions. For these reasons, MAOIs are not recommended to be prescribed along with other antidepressants or certain prescription or nonprescription drugs. Pharmacologic options are limited for individuals with TRD, however, and there is a paucity of data on the efficacy of MAOIs in combination with other antidepressants for the management of TRD. We performed a search of the PubMed database (inception through January 25, 2015) to identify cases that illustrate the potential utility, as well as risks, of combination treatment with MAOIs and other antidepressants for the management of TRD; 18 articles met the criteria for our search. In addition, we performed a retrospective case series by reviewing the medical records of 29 adults treated for depression with an MAOI plus another psychotropic agent (an antidepressant or stimulant medication) between 2003 and 2012 at a large Midwestern teaching hospital. We compared the findings of the published experience with our local experience to allow for more informed decisions regarding pharmacotherapy in patients with TRD. We separated the local experience into two groups: 15 cases with the selective MAO type B inhibitor selegiline combined with medications presumed to increase the risk of serotonin syndrome and 14 cases with nonselective MAOIs (phenelzine and tranylcypromine) combined with other contraindicated medications. Although risks of

  3. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression.

    PubMed

    Thomas, Samantha J; Shin, Mirae; McInnis, Melvin G; Bostwick, Jolene R

    2015-04-01

    Treatment-resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose for an adequate duration fail to respond. Further, approximately half of adults with major depressive disorder fail to achieve sustained remission despite various medication trials. The utilization of monoamine oxidase inhibitors (MAOIs) for the treatment of depression in clinical practice today is low due to their widely known adverse effects, some of which may be life threatening, and the risk for dietary and drug interactions. For these reasons, MAOIs are not recommended to be prescribed along with other antidepressants or certain prescription or nonprescription drugs. Pharmacologic options are limited for individuals with TRD, however, and there is a paucity of data on the efficacy of MAOIs in combination with other antidepressants for the management of TRD. We performed a search of the PubMed database (inception through January 25, 2015) to identify cases that illustrate the potential utility, as well as risks, of combination treatment with MAOIs and other antidepressants for the management of TRD; 18 articles met the criteria for our search. In addition, we performed a retrospective case series by reviewing the medical records of 29 adults treated for depression with an MAOI plus another psychotropic agent (an antidepressant or stimulant medication) between 2003 and 2012 at a large Midwestern teaching hospital. We compared the findings of the published experience with our local experience to allow for more informed decisions regarding pharmacotherapy in patients with TRD. We separated the local experience into two groups: 15 cases with the selective MAO type B inhibitor selegiline combined with medications presumed to increase the risk of serotonin syndrome and 14 cases with nonselective MAOIs (phenelzine and tranylcypromine) combined with other contraindicated medications. Although risks of

  4. Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment

    SciTech Connect

    Garcia-Sevilla, J.A.; Zis, A.P.; Hollingsworth, P.J.; Greden, J.F.; Smith, C.B.

    1981-12-01

    The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors.

  5. Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

    PubMed Central

    Murrough, James W; Burdick, Katherine E; Levitch, Cara F; Perez, Andrew M; Brallier, Jess W; Chang, Lee C; Foulkes, Alexandra; Charney, Dennis S; Mathew, Sanjay J; Iosifescu, Dan V

    2015-01-01

    The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current study, 62 patients (mean age=46.2±12.2) with TRD free of concomitant antidepressant medication underwent neurocognitive assessments using components of the MATRICS Consensus Cognitive Battery (MCCB) before and after a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in a 2:1 fashion under double-blind conditions and underwent depression symptom assessments at 24, 48, 72 h, and 7 days post treatment using the Montgomery–Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment was conducted once at 7 days. Neurocognitive performance improved following the treatment regardless of treatment condition. There was no differential effect of treatment on neurocognitive performance and no association with antidepressant response. Slower processing speed at baseline uniquely predicted greater improvement in depression at 24 h following ketamine (t=2.3, p=0.027), while controlling for age, depression severity, and performance on other neurocognitive domains. In the current study, we found that ketamine was devoid of adverse neurocognitive effects at 7 days post treatment and that slower baseline processing speed was associated with greater antidepressant response. Future studies are required to further define the neurocognitive profile of ketamine in clinical samples and to identify clinically useful response moderators. PMID:25374095

  6. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

    PubMed

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

    2016-01-01

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators. PMID:27219347

  7. Antidepressant treatment differentially affects the phenotype of high and low stress reactive mice.

    PubMed

    Surget, Alexandre; Van Nieuwenhuijzen, Petra S; Heinzmann, Jan-Michael; Knapman, Alana; McIlwrick, Silja; Westphal, Willy-Paul; Touma, Chadi; Belzung, Catherine

    2016-11-01

    Modelling key endophenotypes can be a powerful approach to gain insight into mechanisms underlying the aetiology and pathophysiology of neuropsychiatric disorders. Based on evidence of stress hormone system dysregulations in depression, the Stress Reactivity (SR) mouse model has been generated by a selective breeding approach for extremes in HPA axis reactivity, resulting in high (HR), intermediate (IR) and low (LR) reactive mice. The characterisation of their phenotypic alterations has highlighted many similarities of HR and LR mice with the melancholic and atypical depression, respectively. We therefore aimed to examine whether the antidepressant fluoxetine (10 mg/kg/day i.p., 4-5 weeks) can ameliorate the phenotypic characteristics of HR and LR mice in neuroendocrine functions (HPA axis basal activity, stress reactivity, negative feedback), emotional reactivity/coping-strategy (open field, forced swim tests), spatial learning/memory (Morris water-maze) and hippocampal neurogenesis. Line differences in HPA axis reactivity were maintained under fluoxetine treatment. However, we observed fluoxetine effects on glucocorticoid-induced negative feedback, stress-coping behaviours, cognitive functions and neurogenesis. Specifically, our results revealed line-dependent consequences of fluoxetine treatment: (1) an amelioration of the 'melancholic-like' features of HR mice (reversing the negative feedback resistance, the hyperactive coping style and the memory deficits; increasing hippocampal neurogenesis); (2) an exacerbation of the phenotypic deviations of LR mice (increasing their pronounced negative feedback and passive coping style). Thus, these findings support the predictive validity of antidepressant treatment in the HR mouse line and emphasize the translational value of the SR mouse model for the development of therapeutic strategies based on endophenotype-driven classifications.

  8. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment

    PubMed Central

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C -C; Cole, S W

    2016-01-01

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1–4 (EGR1–4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators. PMID:27187237

  9. 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.

  10. 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 +…

  11. Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

    PubMed

    Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

    2016-08-30

    The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. PMID:27366831

  12. Antidepressant-like properties of prepro-TRH 178-199: acute effects in the forced swim test.

    PubMed

    Redei, E; Organ, M; Hart, S

    1999-11-01

    This study examined the central effects of rat prepro-TRH 178-199, a peptide with corticotropin release inhibiting activity at the pituitary, on the Porsolt forced swim test (FST) of depressive behavior in rats. Subacute intracerebroventricular administration of prepro-TRH 178-199 dose-responsively reduced floating and increased active behaviors in the FST. Chronic administration of 6 microg/kg prepro-TRH 178-199 decreased floating more than subacute treatment, but there were no significant differences between chronic and subacute treatment effects on active behavior. Biological activity of this peptide resides in the C-terminal fragment as prepro-TRH 178-199 and prepro-TRH 191-199 were equally potent in the FST. These data suggest that endogenous prepro-TRH 178-199 with its antidepressant-like activity might contribute to the etiology or manifestation of depressive behavior.

  13. The effects of antidepressant treatment on resting-state functional brain networks in patients with major depressive disorder.

    PubMed

    Wang, Li; Xia, Mingrui; Li, Ke; Zeng, Yawei; Su, Yunai; Dai, Wenji; Zhang, Qinge; Jin, Zhen; Mitchell, Philip B; Yu, Xin; He, Yong; Si, Tianmei

    2015-02-01

    Although most knowledge regarding antidepressant effects is at the receptor level, the neurophysiological correlates of these neurochemical changes remain poorly understood. Such an understanding could benefit from elucidation of antidepressant effects at the level of neural circuits, which would be crucial in identifying biomarkers for monitoring treatment efficacy of antidepressants. In this study, we recruited 20 first-episode drug-naive major depressive disorder (MDD) patients and performed resting-state functional magnetic resonance imaging (MRI) scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor-escitalopram. Twenty healthy controls (HCs) were also scanned twice with an 8-week interval. Whole-brain connectivity was analyzed using a graph-theory approach-functional connectivity strength (FCS). The analysis of covariance of FCS was used to determine treatment-related changes. We observed significant group-by-time interaction on FCS in the bilateral dorsomedial prefrontal cortex and bilateral hippocampi. Post hoc analyses revealed that the FCS values in the bilateral dorsomedial prefrontal cortex were significantly higher in the MDD patients compared to HCs at baseline and were significantly reduced after treatment; conversely, the FCS values in the bilateral hippocampi were significantly lower in the patients at baseline and were significantly increased after treatment. Importantly, FCS reduction in the dorsomedial prefrontal cortex was significantly correlated with symptomatic improvement. Together, these findings provided evidence that this commonly used antidepressant can selectively modulate the intrinsic network connectivity associated with the medial prefrontal-limbic system, thus significantly adding to our understanding of antidepressant effects at a circuit level and suggesting potential imaging-based biomarkers for treatment evaluation in MDD. PMID:25332057

  14. Possible Associations of NTRK2 Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach

    PubMed Central

    Hennings, Johannes M.; Kohli, Martin A.; Czamara, Darina; Giese, Maria; Eckert, Anne; Wolf, Christiane; Heck, Angela; Domschke, Katharina; Arolt, Volker; Baune, Bernhard T.; Horstmann, Sonja; Brückl, Tanja; Klengel, Torsten; Menke, Andreas; Müller-Myhsok, Bertram; Ising, Marcus; Uhr, Manfred; Lucae, Susanne

    2013-01-01

    Background Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. Methods We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. Results In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (Pcorr = .018, Pcorr = .015 and Pcorr = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients. Conclusions/Limitations Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies. PMID:23750220

  15. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment

    PubMed Central

    Shabel, Steven J.; Proulx, Christophe D.; Piriz, Joaquin; Malinow, Roberto

    2015-01-01

    The lateral habenula (LHb), a key regulator of monoaminergic brain regions, is activated by negatively-valenced events. Its hyperactivity is associated with depression. While enhanced excitatory input to the LHb has been linked to depression, little is known about inhibitory transmission. We discovered that GABA is co-released with its functional opponent, glutamate, from long-range basal ganglia inputs (which signal negative events) to limit LHb activity in rodents. At this synapse, the balance of GABA/glutamate signaling is shifted towards reduced GABA in a model of depression and increased GABA by antidepressant treatment. GABA and glutamate co-release therefore controls LHb activity, and regulation of this remarkable form of transmission may be important for determining the impact of negative life events on mood and behavior. PMID:25237099

  16. Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program

    PubMed Central

    Friedrich, Michaela-Elena; Akimova, Elena; Huf, Wolfgang; Konstantinidis, Anastasios; Papageorgiou, Konstantinos; Winkler, Dietmar; Toto, Sermin; Greil, Waldemar; Grohmann, Renate; Kasper, Siegfried

    2016-01-01

    Background: Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic. Methods: This observational study is based on data of Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries (Austria, Germany, and Switzerland) recording severe drug reactions in psychiatric inpatients. Of 184234 psychiatric inpatients treated with antidepressants between 1993 and 2011 in 80 psychiatric hospitals, 149 cases of drug-induced liver injury (0.08%) were reported. Results: The study revealed that incidence rates of drug-induced liver injury were highest during treatment with mianserine (0.36%), agomelatine (0.33%), and clomipramine (0.23%). The lowest probability of drug-induced liver injury occurred during treatment with selective serotonin reuptake inhibitors ([0.03%), especially escitalopram [0.01%], citalopram [0.02%], and fluoxetine [0.02%]). The most common clinical symptoms were nausea, fatigue, loss of appetite, and abdominal pain. In contrast to previous findings, the dosage at the timepoint when DILI occurred was higher in 7 of 9 substances than the median overall dosage. Regarding liver enzymes, duloxetine and clomipramine were associated with increased glutamat-pyruvat-transaminase and glutamat-oxalat-transaminase values, while mirtazapine hardly increased enzyme values. By contrast, duloxetine performed best in terms of gamma-glutamyl-transferase values, and trimipramine, clomipramine, and venlafaxine performed worst. Conclusions: Our findings suggest that selective serotonin reuptake inhibitors are less likely than the other antidepressants, examined in this study, to precipitate drug-induced liver injury, especially in patients with preknown liver dysfunction. PMID:26721950

  17. The Effect of Antidepressant Treatment on HIV and Depression Outcomes: The SLAM DUNC Randomized Trial

    PubMed Central

    PENCE, Brian W.; GAYNES, Bradley N.; ADAMS, Julie L.; THIELMAN, Nathan M.; HEINE, Amy D.; MUGAVERO, Michael J.; MCGUINNESS, Teena; RAPER, James L.; WILLIG, James H.; SHIREY, Kristen G.; OGLE, Michelle; TURNER, Elizabeth L.; QUINLIVAN, E. Byrd

    2015-01-01

    Background Depression is a major barrier to HIV treatment outcomes. Objective Test whether antidepressant management decision support integrated into HIV care improves antiretroviral adherence and depression morbidity. Design Pseudo-cluster randomized trial. Setting Four US infectious diseases clinics. Participants HIV-infected adults with major depressive disorder. Intervention Measurement-Based Care: depression care managers used systematic metrics to give HIV primary-care clinicians standardized antidepressant treatment recommendations. Measurements Primary: Antiretroviral medication adherence (monthly unannounced telephone-based pill counts for 12m). Primary timepoint: 6m. Secondary: Depressive severity, depression remission, depression-free days, measured quarterly for 12m. Results From 2010-2013, 149 participants were randomized to intervention and 155 to usual care. Participants were mostly male, Black non-Hispanic, unemployed, and virally suppressed with high baseline self-reported antiretroviral adherence and depressive severity. Over follow-up, no differences between arms in antiretroviral adherence or other HIV outcomes were apparent. At 6 months, depressive severity was lower among intervention participants than usual care (mean difference −3.7 [95% CI: −5.6, −1.7]), probability of depression remission was higher (risk difference 13% [1%, 25%]), and suicidal ideation was lower (RD −18% [−30%, −6%]). By 12 months the arms had comparable mental health outcomes. Intervention arm participants experienced an average of 29 (95% CI: 1-57) more depression-free days over 12 months. Conclusions In the largest trial of its kind among HIV-infected adults, MBC did not improve HIV outcomes, possibly because of high baseline adherence, but achieved clinically significant depression improvements and increased depression-free days. MBC may be an effective, resource-efficient approach to reducing depression morbidity among HIV patients. PMID:26134881

  18. The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

    PubMed

    Kaminska, K; Rogoz, Z

    2016-06-01

    Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

  19. The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

    PubMed

    Kaminska, K; Rogoz, Z

    2016-06-01

    Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

  20. Disparities in Depressive Symptoms and Antidepressant Treatment by Gender and Race/Ethnicity among People Living with HIV in the United States

    PubMed Central

    Crane, Heidi M.; Christopoulos, Katerina; Fredericksen, Rob J.; Gaynes, Bradley N.; Heine, Amy; Mathews, W. Christopher; Moore, Richard; Napravnik, Sonia; Safren, Steven; Mugavero, Michael J.

    2016-01-01

    Objective To describe disparities along the depression treatment cascade, from indication for antidepressant treatment to effective treatment, in HIV-infected individuals by gender and race/ethnicity. Methods The Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort includes 31,000 HIV-infected adults in routine clinical care at 8 sites. Individuals were included in the analysis if they had a depressive symptoms measure within one month of establishing HIV care at a CNICS site. Depressive symptoms were measured using the validated Patient Health Questionnaire-9 (PHQ-9). Indication for antidepressant treatment was defined as PHQ-9 ≥ 10 or a current antidepressant prescription. Antidepressant treatment was defined as a current antidepressant prescription. Evidence-based antidepressant treatment was considered treatment changes based on a person’s most recent PHQ-9, in accordance with clinical guidelines. We calculated the cumulative probability of moving through the depression treatment cascade within 24 months of entering CNICS HIV care. We used multivariable Cox proportional hazards models to estimate associations between gender, race/ethnicity, and a range of depression outcomes. Results In our cohort of HIV-infected adults in routine care, 47% had an indication for antidepressant treatment. Significant drop-offs along the depression treatment cascade were seen for the entire study sample. However, important disparities existed. Women were more likely to have an indication for antidepressant treatment (HR 1.54; 95% CI 1.34, 1.78), receive antidepressant treatment (HR 2.03; 95% CI 1.53, 2.69) and receive evidence-based antidepressant treatment (HR 1.67; 95% CI 1.03, 2.74), even after accounting for race/ethnicity. Black non-Hispanics (HR 0.47, 95% CI 0.35, 0.65), Hispanics (HR 0.63, 95% CI 0.44, 0.89) and other race/ethnicities (HR 0.35, 95% CI 0.17, 0.73) were less likely to initiate antidepressant treatment, compared to white

  1. Changes in the neural correlates of implicit emotional face processing during antidepressant treatment in major depressive disorder.

    PubMed

    Victor, Teresa A; Furey, Maura L; Fromm, Stephen J; Öhman, Arne; Drevets, Wayne C

    2013-11-01

    An emerging hypothesis regarding the mechanisms underlying antidepressant pharmacotherapy suggests that these agents benefit depressed patients by reversing negative emotional processing biases (Harmer, 2008). Neuropsychological indices and functional neuroimaging measures of the amygdala response show that antidepressant drugs shift implicit and explicit processing biases away from the negative valence and toward the positive valence. However, few studies have explored such biases in regions extensively connected with the amygdala, such as the pregenual anterior cingulate cortex (pgACC) area, where pre-treatment activity consistently has predicted clinical outcome during antidepressant treatment. We used functional magnetic resonance imaging (fMRI) to investigate changes in haemodynamic response patterns to positive vs. negative stimuli in patients with major depressive disorder (MDD) under antidepressant treatment. Participants with MDD (n = 10) underwent fMRI before and after 8 wk sertraline treatment; healthy controls (n = 10) were imaged across an equivalent interval. A backward masking task was used to elicit non-conscious neural responses to sad, happy and neutral face expressions. Haemodynamic responses to emotional face stimuli were compared between conditions and groups in the pgACC. The response to masked-sad vs. masked-happy faces (SN-HN) in pgACC in the depressed subjects was higher in the pre-treatment condition than in the post-treatment condition and this difference was significantly greater than the corresponding change across time in the controls. The treatment-associated difference was attributable to an attenuated response to sad faces and an enhanced response to happy faces. Pre-treatment pgACC responses to SN-HN correlated positively with clinical improvement during treatment. The pgACC participates with the amygdala in processing the salience of emotional stimuli. Treatment-associated functional changes in this limbic network may influence

  2. From Pharmacogenetics to Pharmacogenomics: The Way Toward the Personalization of Antidepressant Treatment

    PubMed Central

    Fabbri, Chiara; Porcelli, Stefano; Serretti, Alessandro

    2014-01-01

    Objective: Major depressive disorder is the most common psychiatric disorder, worldwide, yet response and remission rates are still unsatisfactory. The identification of genetic predictors of antidepressant (AD) response could provide a promising opportunity to improve current AD efficacy through the personalization of treatment. The major steps and findings along this path are reviewed together with their clinical implications and limitations. Method: We systematically reviewed the literature through MEDLINE and Embase database searches, using any word combination of “antidepressant,” “gene,” “polymorphism,” “pharmacogenetics,” “genome-wide association study,” “GWAS,” “response,” and “adverse drug reactions.” Experimental works and reviews published until March 2012 were collected and compared. Results: Numerous genes pertaining to several functional systems were associated with AD response. The more robust findings were found for the following genes: solute carrier family 6 (neurotransmitter transporter), member 4; serotonin receptor 1A and 2A; brain-derived neurotrophic factor; and catechol-O-methyltransferase. Genome-wide association studies (GWASs) provided many top markers, even if none of them reached genome-wide significance. Conclusions: AD pharmacogenetics have not produced any knowledge applicable to routine clinical practice yet, as results were mainly inconsistent across studies. Despite this, the rising awareness about methodological deficits of past studies could allow for the identication of more suitable strategies, such as the integration of the GWAS approach with the candidate gene approach, and innovative methodologies, such as pathway analysis and study of depressive endophenotypes. PMID:24881125

  3. Antidepressants for older people: what can we learn from the current evidence base?

    PubMed

    Katona, Cornelius; Bindman, Dorothea C; Katona, Cara P

    2014-10-01

    This paper updates our previous review of the evidence base for managing depression in old age while focusing more specifically on the use of antidepressants. Overall, recent systematic reviews and meta-analyses indicate that antidepressants are effective in the acute treatment of depression in old age but that the superiority of active drug over placebo is quite modest. The depression of Alzheimer's disease is probably not treated effectively with antidepressants. The most consistent evidence is for the effectiveness of continued antidepressant treatment in those depressed patients who respond well to acute treatment. There remains a clear need for more research to identify effective treatments for resistant depression though therapeutic nihilism should be avoided if first-line treatment fails. PMID:24975955

  4. Anxiolytic-like effects of antidepressants after acute administration in a four-plate test in mice.

    PubMed

    Hascoët, M; Bourin, M; Colombel, M C; Fiocco, A J; Baker, G B

    2000-02-01

    The four-plate test (FPT) is an animal model of anxiety based on stress caused by unconditioned fear. An increase of spontaneous punished behavior was used as a measure to determine the anxiolytic effects of various antidepressants (ADs). In the present study. ADs with different mechanisms of action, including tricyclics, selective serotonin reuptake inhibitors (SSRIs), a monoamine oxidase inhibitor (MAOI), and atypicals, were studied in the FPT to evaluate their anxiolytic-like effects following acute administration. The number of punished crossings was dramatically increased by the SSRIs citalopram, fluvoxamine, and paroxetine, but not fluoxetine. The mixed 5-HT/NE reuptake inhibitors, milnacipran and venlafaxine, also demonstrated strong antipunishment effects. The specific NE reuptake inhibitors, desipramine and maprotiline, and the atypical AD trazodone, enhanced freezing behavior, suggesting anxiogenic-like behavior. It was concluded that, in the FPT, a model based on spontaneous response, where animals are exposed to an aversive environment from which they can only escape by being motionless, this kind of behavior might be related to anticipatory anxiety. In this situation, ADs acting preferentially on 5-HT transmission possessed clear anxiolytic like effects. The balance between the two transmitters, 5-HT and NE, seemed to be a crucial factor.

  5. Electro-peroxone treatment of the antidepressant venlafaxine: Operational parameters and mechanism.

    PubMed

    Li, Xiang; Wang, Yujue; Zhao, Jian; Wang, Huijiao; Wang, Bin; Huang, Jun; Deng, Shubo; Yu, Gang

    2015-12-30

    Degradation of the antidepressant venlafaxine by a novel electrocatalytic ozonation process, electro-peroxone (E-peroxone), was studied. The E-peroxone treatment involves sparging ozone generator effluent (O2 and O3 gas mixture) into an electrolysis reactor that is equipped with a carbon-polytetrafluoroethylene cathode to electrocatalytically transform O2 in the bubbled gas to H2O2. The in-situ generate H2O2 then reacts with the bubbled O3 to yield OH, which can non-selectively degrade organic compounds rapidly in the solution. Thanks to the significant OH production, the E-peroxone treatment greatly enhanced both venlafaxine degradation and total organic carbon (TOC) removal as compared to ozonation and electrolysis alone. Under optimal reaction conditions, complete venlafaxine degradation and TOC elimination could be achieved within 3 and 120 min of E-peroxone process, respectively. Based on the by-products (e.g., hydroxylated venlafaxine, phenolics, and carboxylic acids) identified by UPLC-UV and UPLC/Q-TOF-mass spectrometry, plausible reaction pathways were proposed for venlafaxine mineralization by the E-peroxone process. The results of this study suggest that the E-peroxone treatment may provide a promising way to treat venlafaxine contaminated water.

  6. [Antidepressants in epilepsy].

    PubMed

    Castaño-Monsalve, Beatriz

    2013-08-01

    Depression is a common condition in patients with epilepsy that entails a deterioration of the quality of life of this population and that, therefore, requires appropriate treatment. The potential risk of antidepressants in relation to the seizure threshold is overestimated by many professionals, and this has an influence when it comes to making the decision to treat them. It sometimes means that the patients do not receive antidepressant drugs. In this regard, the aim of this review is to present the current state of the art in terms of the safety of antidepressants in patients with epilepsy. A search of the medical literature was conducted and, following its analysis, the most significant results are presented. Current information indicates that most antidepressants are safe for epileptic patients at therapeutic doses and that the risk of seizures occurs mainly in cases of overdose. Preferred drugs for treating depression in epilepsy are serotonin reuptake inhibitors. Bupropion and tricyclic antidepressants must be avoided.

  7. Nonnarcotic analgesics and tricyclic antidepressants for the treatment of chronic nonmalignant pain.

    PubMed

    Richlin, D M

    1991-05-01

    Chronic nonmalignant pain is often characterized by multiple treatment failures, a pattern of maladaptive behavior, and depression. Often there is a history of inappropriate and excessive use of medications for pain. Prior and ongoing use of narcotics and sedatives acts to compound and aggravate the chronic pain syndrome. A first step in treatment is controlled withdrawal of these agents. Nonnarcotic analgesics, NSAIDs, and tricyclic antidepressants are commonly employed in patients with chronic pain. Effective use of these agents requires understanding of their pharmacokinetic and pharmacodynamic properties. Use of a fixed-time schedule is necessary to achieve an effective, sustained therapeutic response. Careful patient education and monitoring for side effects and toxicity are necessary, particularly in the elderly and patients with coexisting medical disorders. Incidence of side effects and toxicity may be reduced by choice of drug and modification of dosing regimen. Nonnarcotic analgesics, TCAs, and NSAIDs are seldom effective by themselves in resolving the pain and distress of patients with chronic nonmalignant pain. This is particularly true when maladaptive behavior coexists. A comprehensive multimodal pain management program encompassing additional pain-relieving strategies and behavior-modifying techniques should be considered and utilized in conjunction with medication.

  8. Stress, depression and antidepressant treatment options in patients suffering from multiple sclerosis.

    PubMed

    Schumann, Robert; Adamaszek, Michael; Sommer, Norbert; Kirkby, Kenneth C

    2012-01-01

    Stress constitutes a risk factor for diseases where the immune system plays a significant role. Stress is recognized as a possible trigger for flare ups during the course of multiple sclerosis (MS). The disclosure to the patient of the diagnosis of MS, the commencement of immunomodulatory therapy, and the unpredictability and vagaries of disease progression are all sources of stress. Biological stress systems such as the hypothalamic-pituitary-adrenal system and the sympathetic nervous system may influence the pathogenesis and the disease course of MS. The ability to cope with stress may also be impaired, mediated for example by cognitive deficits or loss of abilities and resources as disease progresses or by the high prevalence of concurrent mood disturbances such as depression and chronic fatigue. Psychiatric comorbidities of MS disease or therapy as well as impairments of coping strategies are underrecognized in clinical practice. Treatment plans for depression among MS patients, as the most common psychiatric comorbidity, should be individualized with integrated approaches. Antidepressants are effective for the treatment of depression in MS patients although further clinical research into the neurobiological and psychological bases of depressive disorders in MS patients is clearly needed. In therapy, coping strategies can be enhanced through multidisciplinary assessment of the various challenges and restrictions imposed by the disease and assisting and supporting the patient in addressing these. Exercise, as a form of positive stress (eustress), also has a role in therapy.

  9. Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants

    PubMed Central

    Li, Dian-Jeng; Tseng, Ping-Tao; Chen, Yen-Wen; Wu, Ching-Kuan; Lin, Pao-Yen

    2016-01-01

    Abstract Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P < 0.001), and the treatment effect was similar to other antidepressants/standard treatments (P = 0.220). There were no significant differences in the dropout rate (P = 0.285) and rate of phase shifting (P = 0.952) between BD patients who received bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other

  10. Enhanced care by community health workers in improving treatment adherence to antidepressant medication in rural women with major depression

    PubMed Central

    Pradeep, Johnson; Isaacs, Anton; Shanbag, Deepthi; Selvan, Sumithra; Srinivasan, Krishnamachari

    2014-01-01

    Background & objectives: Depression remains largely undiagnosed in women residing in rural India and consequently many do not seek help. Moreover, among those who are diagnosed, many do not complete treatment due to high rates of attrition. This study was aimed to compare the effectiveness of enhanced care with usual care in improving treatment seeking and adherence to antidepressant medication in women with depression living in rural India. Methods: Six villages from rural Bangalore were randomized to either community health worker supported enhanced care or usual care. A total of 260 adult depressed women formed the final participants for the analysis. The outcome measures were number of women who sought and completed treatment, number of clinic visits, duration of treatment with antidepressant, changes in severity of depression (HDRS) and changes in quality of life [WHO-QOL (Brev) scale]. Results: A significantly greater number of women from the treatment intervention (TI) group completed the treatment and were on treatment for a longer duration compared to the treatment as usual (TAU) group. However, there were no significant differences in the severity of depression or quality of life between the TI and the TAU groups or between treatment completers and treatment dropouts at six months. Interpretation & conclusions: Enhanced care provided by the trained community health workers to rural women with major depression living in the community resulted in greater number of women seeking help and adhering to treatment with antidepressants. However, despite enhanced care a significant number of rural women diagnosed with depression either did not seek help or discontinued treatment prematurely. These findings have significant public health implications, as untreated depression is associated with considerable disability. PMID:24718398

  11. [The comparative study on the efficacy of the combination of serotonin reuptake inhibitor antidepressants and antipsychotics in the treatment of recurrent depressive disorders].

    PubMed

    D'iakonov, A L; Lobanova, I V

    2012-01-01

    A combination of serotonin reuptake inhibitor antidepressants (prozac and stimulaton) with atypical antipsychotics (zyprexa and solian) reduced depression in patients with recurrent depressive disorders during 10 days. The effect was evenly distributed between 10, 20 and 40 days of treatment. Other symptoms had a peculiar dynamics depending on the therapy. By the end of the study, similar effects were achieved for all groups. The addition of antipsychotics to antidepressant treatment insignificantly increased the number of adverse events.

  12. [Treatment and prevention of acute radiation dermatitis].

    PubMed

    Benomar, S; Boutayeb, S; Lalya, I; Errihani, H; Hassam, B; El Gueddari, B K

    2010-06-01

    Acute radiation dermatitis is a common side-effect of radiotherapy which often necessitates interruption of the therapy. Currently, there is no general consensus about its prevention or about the treatment of choice. The goal of this work was to focus on optimal methods to prevent and manage acute skin reactions related to radiation therapy and to determine if there are specific topical or oral agents for the prevention of this acute skin reaction. The prevention and the early treatment are the two focus points of the management of the acute radiation dermatitis.

  13. Treatment effects of serotonergic and noradrenergic antidepressants on the intensity dependence of auditory ERP components in major depression.

    PubMed

    Linka, Thomas; Sartory, Gudrun; Wiltfang, Jens; Müller, Bernhard W

    2009-09-29

    The intensity dependent amplitude change of auditory evoked potentials (IDAP), an assumed indicator of the level of central nervous serotonergic neurotransmission, was measured in major depressive disorder (MDD, DSM-IV: 296.2, 296.3; APA 1994) before and after treatment with either a selective serotonin reuptake inhibitor or a selective noradrenaline reuptake inhibitor antidepressant and compared with the results of a healthy control group. Auditory evoked P1, N1, P2, P1/N1 and N1/P2 peak-to-peak amplitudes were evaluated in 26 in-patients with MDD prior to and after antidepressant treatment with citalopram (24 days, n=14) or reboxetine (25 days, n=12), and in 43 healthy control subjects. Clinical symptoms of MDD were assessed by means of standardized psychiatric rating scales (CGI, HDRS, HAMA and BDI). The IDAP within the control group remained stable over 24 days (N1 amplitude slope retest ANOVA p=.79). Neither applied antidepressants nor decrease of HDRS total score during treatment had a significant effect on the IDAP in the patients' sample. The conclusion that the IDAP does not reflect the temporary depressive state in MDD is discussed.

  14. Chronic antidepressant treatment exerts sexually dimorphic immunomodulatory effects in an experimental model of major depression: do females lack an advantage?

    PubMed

    Pitychoutis, Pothitos M; Griva, Eirini; Ioannou, Kyriaki; Tsitsilonis, Ourania E; Papadopoulou-Daifoti, Zeta

    2009-10-01

    Major depression is a stress-related disorder that affects about 20% of the population, with women outnumbering men by 2:1. However, research focusing on stress/antidepressant-related immunomodulation overlooks sex differences, although an established sexual dimorphism also characterizes the immune system. We report for the first time that both chronic clomipramine treatment (10 mg/kg, twice daily) and chronic mild stress (CMS) application in rats, exert sexually dimorphic effects on cellular immunoreactivity (natural killer and lymphokine-activated killer cell cytotoxicity and interleukin-2-induced T-cell proliferation), with females presenting a relatively immunosuppressed phenotype compared to males. Moreover, following chronic antidepressant treatment, thymic monoamines presented sex-related alterations, as well as intriguing associations with peripheral T-cell responses. This study highlights the sex-related effects of chronic clomipramine treatment and CMS application on the cellular arm of immunity, and represents a preliminary exposé of a thymus-dependent route pertaining to the interactions between antidepressants and the immune system.

  15. Desvenlafaxine succinate: a newer antidepressant for the treatment of depression and somatic symptoms.

    PubMed

    Seo, Ho-Jun; Sohi, Manmohandeep Singh; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

    2010-01-01

    Desvenlafaxine succinate (DVS) is one of several serotonin-norepinephrine reuptake inhibitors (SNRIs). Others are venlafaxine hydrochloride, milnacipran, and duloxetine. Desvenlafaxine has been approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) based on a number of randomized, placebo-controlled clinical trials. Clinical studies have investigated the efficacy of DVS in doses ranging from 50 to 400 mg/day for the treatment of MDD in adult outpatients. The effects of DVS 50 mg/day have been clearly distinguished from placebo in the reduction of MDD symptoms in such clinical trials. No additional therapeutic benefits were found at doses > 50 mg/day. The recommended dose of DVS ranges from 50 to 100 mg. Desvenlafaxine is currently the third SNRI approved by the FDA for this indication. Preliminary evidence also suggests the clinical usefulness of DVS in the treatment of vasomotor symptoms of menopause, anxiety symptoms, and painful physical symptoms. The modified pharmacokinetic and pharmacodynamic profiles of DVS differentiate this drug from the original product, venlafaxine. Significant points of difference, compared with venlafaxine, are once-daily dosing and the achievement of steady-state plasma concentrations within 4 to 5 days. To summarize, current evidence indicates that DVS has proven efficacy, acceptable safety and tolerability profiles, convenient dosing, and minimal impact on the cytochrome P450 enzyme system. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other selective serotonin noradrenaline reuptake inhibitors. Desvenlafaxine succinate has demonstrated its efficacy for treating MDD but its variable efficacy, as shown in individual studies, limited long-term data, and its different risk-to-benefit ratio compared with earlier antidepressants, means that further investigation of this drug is necessary.

  16. Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

    PubMed Central

    Alves, José Carlos; Rego, Raquel Garcia

    2016-01-01

    Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice. PMID:27807450

  17. Dopamine, depression and antidepressants.

    PubMed

    Dailly, Eric; Chenu, Franck; Renard, Caroline E; Bourin, Michel

    2004-12-01

    Abstract The relationship between depression and dopamine deficiency in the mesolimbic pathway has been hypothesized for many years. The experimental studies with animal models of depression and the human studies implicate the role of the dopamine system in depression. Not only do dopaminergic receptor agonists, but also antagonists such as olanzapine exhibit antidepressant effects associated with standard antidepressants in patients with treatment-resistant depression. This paradoxical result suggests that further investigations are necessary to understand the role played by dopamine in depression.

  18. Rapid improvement of depressive symptoms in suicide attempters following treatment with milnacipran and tricyclic antidepressants - a case series.

    PubMed

    Kirino, Eiji; Gitoh, Masao

    2011-01-01

    Suicide is a serious social problem in many countries, including Japan. The majority of people who commit suicide suffer from depression. Suicide attempt patients suffering from serious physical injuries are initially treated in hospital emergency departments. The present post hoc analysis examined data from patients admitted to an emergency hospital for treatment of physical injuries, resulting from a suicide attempt, and initial psychiatric treatment for depression and prevention of future suicide attempts. The effects on depressive symptoms were studied in two groups of patients using the 17-item Hamilton depression scale (HAMD). One group (n = 6) had received intravenous tricyclic antidepressants (TCA) (amitriptyline or clomipramine) while the other group (n = 7) had been treated orally with milnacipran, a serotonin and norepinephrine reuptake inhibitor antidepressant. Prior to treatment the four highest scoring items on the HAMD scale were the same in both groups namely, item 1 (depressed mood), item 3 (suicidality), item 7 (interest in work and activities), and item 10 (psychic anxiety). After 1 week of treatment, mean global HAMD scores were significantly reduced in both groups. Treatment resulted in a significant reduction of five HAMD items in the TCA group, whereas in the milnacipran group 12 HAMD items were significantly reduced. Suicidality (item 3) was significantly improved by 1 week treatment with milnacipran, but not by TCAs. Milnacipran rapidly improved a wide range of depressive symptoms, including suicidality within the first week. The improvement with milnacipran would appear to be, at least, equivalent to that achieved with TCAs, possibly affecting a wider range of symptoms. Since milnacipran has been shown in comparative studies to be better tolerated than TCAs, this antidepressant offers an interesting option for the treatment of suicidal patients in an emergency setting. PMID:22247614

  19. Effects of single and repeated treatment with antidepressants on apomorphine-induced yawning in the rat: the implication of alpha-1 adrenergic mechanisms in the D-2 receptor function.

    PubMed

    Delini-Stula, A; Hunn, C

    1990-01-01

    Acute (10 or 20 mg/kg IP) and subchronic (2 x 5 or 10 mg/kg IP daily for 7 days) effects of desipramine, imipramine, maprotiline, (+)- and (-)-oxaprotiline enantiomers as well as selective 5-HT-uptake inhibitors citalopram and ifoxetine on yawning, induced by low doses of apomorphine, were investigated in the rat. In addition, the effects of alpha-1 receptor agonist adrafinil and antagonist prazosin were also tested. After acute treatment, desipramine, the stereoselective NA-uptake inhibiting (+)-enantiomer of oxaprotiline, and the alpha-1 agonist adrafinil, markedly and significantly suppressed yawning. Prazosin, in contrast, clearly potentiated it. This potentiating effect was abolished by the pretreatment with (+)-oxaprotiline and adrafinil. Other drugs were inactive. After subchronic administration, yawning was antagonized by NA-uptake-inhibiting antidepressants, including imipramine and maprotiline. By comparison to the acute treatment, the inhibitory effects of desipramine and (+)-oxaprotiline were considerably enhanced. Neither selective 5-HT-uptake inhibitors nor (-)-oxaprotiline (levoprotiline) were active. Antidepressants therefore modulate the functional activity of D-2 receptors, activated by low doses of apomorphine, predominantly by the virtue of their noradrenergic enhancing properties. This modulatory effect appears to be mediated by alpha-1 adrenergic receptors. PMID:1971448

  20. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  1. Treatment Options for Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  2. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  3. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  4. Antidepressants in the treatment of depression/depressive symptoms in cancer patients: a systematic review and meta-analysis

    PubMed Central

    2013-01-01

    Background Over the past thirty years a number of studies have suggested that antidepressants can be effective in the treatment of depressive symptoms in patients with cancer. The aim of this paper was to review randomized controlled trials (RCTs) and to perform a meta-analysis in order to quantify their overall effect. Methods Pubmed and the Cochrane libraries were searched for the time period between 1980 and 2010. Results Nine RCTs were identified and reviewed. Six of them (with a total of 563 patients) fulfilled the criteria for meta-analysis, but exhibited an unclear risk for bias. The estimated effect size was 1.56 with 95% CI: 1.07- 2.28 (p= 0.021). There were no differences in discontinuation rates between antidepressants and placebo groups (RR= 0.86 with 95% CI 0.47- 1.56, p=0.62). Conclusions This meta-analysis suggests that antidepressants can be effective in treating depressive symptoms beside clinical depression. When considering the risk of side effects and interactions and the heterogeneity among the mostly small studies, a general recommendation cannot be made until well-controlled studies are conducted. PMID:23679841

  5. [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

  6. [Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

    PubMed

    Kudryashov, N V; Kalinina, T S; Voronina, T A

    2015-02-01

    The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

  7. Different molecular forms of cholecystokinin and CCKB receptor binding in the rat brain after chronic antidepressant treatment.

    PubMed

    Harro, J; Löfberg, C; Pähkla, R; Matto, V; Rägo, L; Oreland, L; Allikmets, L

    1997-01-01

    Cholecystokinin (CCK) is a neuropeptide recently implicated in affective disorders. This study aimed at measuring the levels of different molecular forms of CCK and the binding characteristics of CCKB receptors in the rat brain after three weeks of treatment with four different antidepressants, imipramine, amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per day i.p.). Chronic treatment with imipramine and desipramine had a significant immobility-reducing effect in the Porsolt's swim test. The effect of amitriptyline, albeit in the same direction, was not significant, and citalopram had no effect in this test. In the elevated plus-maze test of anxiety, all drugs tended to increase the number of open arm entries and the ratio open/total arm entries, but only the effects of imipramine were statistically significant. None of the treatments affected the total levels of CCK or the levels of CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was no effect of the treatments on CCKB receptor binding in the frontal cortex, hippocampus, or striatum. Imipramine and amitriptyline, however, increased the affinity of CCKB receptor binding in the hypothalamus. Thus, no consistent effect of chronic antidepressant treatment on the CCK-ergic neurotransmission in the rats was found.

  8. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    PubMed

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice. PMID:24125781

  9. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    PubMed

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice.

  10. Endoscopic Treatment of Recurrent Acute Pancreatitis and Smoldering Acute Pancreatitis.

    PubMed

    Das, Rohit; Yadav, Dhiraj; Papachristou, Georgios I

    2015-10-01

    Recurrent acute pancreatitis (RAP) is a challenging condition that can lead to chronic pancreatitis and long-term morbidity. Etiology-based treatment can potentially have an impact on the natural history of RAP and its progression to chronic pancreatitis. In cases of divisum-associated RAP and idiopathic RAP, several studies have been performed to evaluate the efficacy of endoscopic therapy in alleviation of symptoms and frequency of AP events. This review discusses the literature available on these topic as well as touching on the role of endoscopic therapy in smoldering acute pancreatitis.

  11. 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

  12. Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder

    PubMed Central

    Korgaonkar, Mayuresh S.; Rekshan, William; Gordon, Evian; Rush, A. John; Williams, Leanne M.; Blasey, Christine; Grieve, Stuart M.

    2014-01-01

    Background Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs. Methods 157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants. Findings Overall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume < 14 · 8 mL & right angular gyrus volume > 6 · 3 mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle < 0 · 63, right superior fronto-occipital fasciculus < 0 · 54 and right superior longitudinal fasciculus < 0 · 50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters. Interpretation Pretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients. Funding Brain Resource Ltd is the sponsor for the i

  13. Social stress-induced hypothyroidism is attenuated by antidepressant treatment in rats.

    PubMed

    Olivares, Emerson L; Silva-Almeida, Cláudio; Pestana, Fernanda M; Sonoda-Côrtes, Rafael; Araujo, Iracema G; Rodrigues, Nayana C; Mecawi, André S; Côrtes, Wellington S; Marassi, Michelle P; Reis, Luis Carlos; Rocha, Fábio F

    2012-01-01

    Although serotonergic system has been classically implicated in mood modulation, there has been relatively little study on the relationship between this system and thyroid hormones (TH) economy in stress models. When TH are studied, the effects of stress on thyroid function seems to be complex and depend on the kind and time of stress which counts for the elusiveness of mechanisms underlying changes in TH economy. Herein, we hypothesized that serum TH are affected in a time-dependent fashion after repeated social stressful stimuli and serotonergic system is implicated in these changes. Therefore, we aimed to investigate the possible alterations in thyroid hormone economy and type 1 (D1) and type 2 (D2) deiodinase activity in a model of social defeat stress. Thereafter, we tested the responsiveness of these changes to fluoxetine treatment. Both short (STS) and a long-term (LTS) stress were performed. Blood samples were drawn just before and 1 (STS) or 4 and 8 weeks (LTS) after the beginning of stress to assess serum T4, T3 and corticosterone. Deiodinases activity was assessed at the end of each protocol. Stress-induced behavior studied in open field arena and hypercorticosteronemia were mainly observed in LTS (week 4). Stress-induced behavior was associated to hypothyroidism which occurred before, since week 1 in stressed group. Serum TH was restored to control levels in week 8, when behavior changes were not observed anymore, and was mainly associated with high brown adipose tissue D2 activity since thyroid and liver D1 activity were low or normal in the STS and LTS respectively in stressed rats compared to control. Antidepressant study revealed that fluoxetine treatment (10mg/kg po during four weeks) fully reversed stress-induced behavior and normalized serum T4, but not T3 levels and hypercorticosteronemia in stressed group compared to control. The current work adds new concepts concerning TH metabolism changes induced by social stress and suggests that

  14. 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

  15. GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality.

    PubMed

    Anderberg, Rozita H; Richard, Jennifer E; Hansson, Caroline; Nissbrandt, Hans; Bergquist, Filip; Skibicka, Karolina P

    2016-03-01

    Glucagon-like peptide 1 (GLP-1), produced in the intestine and hindbrain, is known for its glucoregulatory and appetite suppressing effects. GLP-1 agonists are in clinical use for treatment of type 2 diabetes and obesity. GLP-1, however, may also affect brain areas associated with emotionality regulation. Here we aimed to characterize acute and chronic impact of GLP-1 on anxiety and depression-like behavior. Rats were subjected to anxiety and depression behavior tests following acute or chronic intracerebroventricular or intra-dorsal raphe (DR) application of GLP-1 receptor agonists. Serotonin or serotonin-related genes were also measured in the amygdala, DR and the hippocampus. We demonstrate that both GLP-1 and its long lasting analog, Exendin-4, induce anxiety-like behavior in three rodent tests of this behavior: black and white box, elevated plus maze and open field test when acutely administered intraperitoneally, into the lateral ventricle, or directly into the DR. Acute central GLP-1 receptor stimulation also altered serotonin signaling in the amygdala. In contrast, chronic central administration of Exendin-4 did not alter anxiety-like behavior but significantly reduced depression-like behavior in the forced swim test. Importantly, this positive effect of Exendin-4 was not due to significant body weight loss and reduced food intake, since rats pair-fed to Exendin-4 rats did not show altered mood. Collectively we show a striking impact of central GLP-1 on emotionality and the amygdala serotonin signaling that is divergent under acute versus chronic GLP-1 activation conditions. We also find a novel role for the DR GLP-1 receptors in regulation of behavior. These results may have direct relevance to the clinic, and indicate that Exendin-4 may be especially useful for obese patients manifesting with comorbid depression. PMID:26724568

  16. Effects of antidepressant treatment on total antioxidant capacity and free radical levels in patients with major depressive disorder.

    PubMed

    Chang, Cheng-Chen; Lee, Chun-Te; Lan, Tsuo-Hung; Ju, Po-Chung; Hsieh, Yi-Hsien; Lai, Te-Jen

    2015-12-15

    In this prospective study, we investigated the effects of antidepressant therapy on total antioxidant capacity and free radical levels in patients with major depressive disorder (MDD). We recruited thirty-five first-episode patients who met the criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders of MDD and 35 age- and sex-matched healthy controls. Superoxide and hydroxyl radicals were measured to investigate oxidative status and the total radical-trapping antioxidant parameter (TRAP) assay was performed to evaluate antioxidant capacity in healthy controls and in patients before and after receiving a 12-week regimen of sertraline. The severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale (HDRS). Before treatment, the mean HDRS score in patients with MDD was 26.11±4.93. Of the 35 patients with MDD, 19 (54.29%) completed the 12-week treatment regimen and all achieved remission. Patients with MDD had significantly lower TRAP baseline values than healthy controls. After adjusting for age, sex, occupation, education and marital status, we found that HDRS score was negatively correlated with TRAP value and level of superoxide radicals. After treatment, the MDD group demonstrated significantly higher TRAP values and significantly lower levels of superoxide and hydroxyl radicals. In conclusion, MDD patients are accompanied by lowered antioxidant capacity than healthy individuals. Antidepressant treatment for 12 weeks results in increased antioxidant capacity and a decrease in circulating free radicals.

  17. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  18. Acute scurvy during treatment with interleukin-2.

    PubMed

    Alexandrescu, D T; Dasanu, C A; Kauffman, C L

    2009-10-01

    The association of vitamin C deficiency with nutritional factors is commonly recognized. However, an acute form of scurvy can occur in patients with an acute systemic inflammatory response, which is produced by sepsis, medications, cancer or acute inflammation. The frequency of acute hypovitaminosis C in hospitalized patients is higher than previously recognized. We report the occurrence of acute signs and symptoms of scurvy (perifollicular petechiae, erythema, gingivitis and bleeding) in a patient hospitalized for treatment of metastatic renal-cell carcinoma with high-dose interleukin-2. Concomitantly, serum vitamin C levels decreased to below normal. Better diets and longer lifespan may result a lower frequency of acute scurvy and a higher frequency of scurvy associated with systemic inflammatory responses. Therefore, increased awareness of this condition can lead to early recognition of the cutaneous signs of acute scurvy in hospitalized patients with acute illnesses or in receipt of biological agents, and prevent subsequent morbidity such as bleeding, anaemia, impaired immune defences, oedema or neurological symptoms.

  19. [Treatment of chronic back pain with antidepressant cymbalta: an experimental study].

    PubMed

    Voznesenskaia, T G; Leonova, A R; Kaverina, I V

    2007-01-01

    Thirty-two patients at the acute stage of chronic back pain have been studied. Cymbalta was used as a monotherapy in dosage 60 mg daily during 6 weeks simultaneously with traditional non-pharmacological therapy. Treatment efficacy was assessed using self-rating methods and quantitative scales measuring pain intensity as well as Spilberger trait/state anxiety inventory, Beck depression scale, Plutchik scale measuring psychological defense mechanisms, quality of sleep, quality of life and evaluation of autonomic dysfunction. The treatment with cymbalta resulted in significant reduction of pain in 90% patients, with full stopping of the syndrome in 10% and marked reduction in 55%. The stopping of pain syndrome was correlated with significant improvement of emotional status and quality of life and sleep normalization of the patients. PMID:18379477

  20. Cardiovascular Adverse Reactions During Antidepressant Treatment: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2010

    PubMed Central

    Spindelegger, Christoph Josef; Papageorgiou, Konstantinos; Grohmann, Renate; Engel, Rolf; Greil, Waldemar; Konstantinidis, Anastasios; Agelink, Marcus Willy; Bleich, Stefan; Ruether, Eckart; Toto, Sermin

    2015-01-01

    Background: Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations. Methods: Of 169 278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Results: Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%), TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure. Conclusions: Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings. PMID:25522416

  1. Treatment of major depressive disorder and dysthymic disorder with antidepressants in patients with comorbid opiate use disorders enrolled in methadone maintenance therapy: a meta-analysis.

    PubMed

    Pedrelli, Paola; Iovieno, Nadia; Vitali, Mario; Tedeschini, Enrico; Bentley, Kate H; Papakostas, George I

    2011-10-01

    Depression and opiate-use disorders (abuse, dependence) often co-occur, each condition complicating the course and outcome of the other. It has been recommended that clinicians prescribe antidepressant therapy for mood symptoms in patients with active substance-use disorders, but whether antidepressants are effective in this specific population is not entirely clear. Therefore, the aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder (DD) with comorbid opiate-use disorders currently in methadone maintenance treatment (MMT). Medline/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the treatment of MDD/DD in patients with comorbid opiate-use disorders currently in MMT. The search was limited to articles published between January 1, 1980, and June 30, 2010 (inclusive). Four manuscripts were found eligible for inclusion in our analysis (n = 317 patients). We found no statistically significant difference in response rates between antidepressant and placebo therapy in trials of MDD/DD patients with comorbid opiate-use disorders currently in MMT (risk ratio for response, 1.182; 95% CI: 0.822-1.700; P = 0.366). These results show no difference in the depressive outcome of patients with comorbid opiate-use disorders on MMT whether they are on medication or placebo. Future studies examining the effectiveness of antidepressants while controlling for several variables such as psychosocial treatment and assessing the specific classes of antidepressants are needed.

  2. Acute antidepressant response to sleep deprivation combined with light therapy is influenced by the catechol-O-methyltransferase Val(108/158)Met polymorphism.

    PubMed

    Benedetti, Francesco; Barbini, Barbara; Bernasconi, Alessandro; Fulgosi, Mara Cigala; Dallaspezia, Sara; Gavinelli, Chiara; Locatelli, Clara; Lorenzi, Cristina; Pirovano, Adele; Radaelli, Daniele; Smeraldi, Enrico; Colombo, Cristina

    2010-02-01

    Catechol-O-methyltransferase (COMT) inactivates norepinephrine and dopamine via methyl conjugation, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity. It is a current area of debate whether rs4680 can influence antidepressant response in major depressive disorder, and whether this influence extends to bipolar depression. Chronotherapeutic interventions, such as sleep deprivation and light therapy, are multi-target in nature and are effective in bipolar depression. Here we studied the effect of rs4680 on response to sleep deprivation combined with light therapy (36 h awake followed by a night of undisturbed sleep, with 10,000 lx light administered for 30 min during the night awake and upon awakening) in 87 bipolar depressed inpatients. Patients who were homozygotic for the Val/Val variant showed a significantly less efficient antidepressant effect after the night awake than those who were heterozygotic and homozygotic for the Met variant. This effect of rs4680 is similar to its observed influence on response to serotonergic and noradrenergic drug treatments in major depressive disorder. This is the first study reporting an influence of rs4680 on antidepressant response in bipolar depression. This finding supports the hypothesis of a major role for catecholamines in the mechanism of action of chronotherapeutics, and for rs4680 in modulating this effect.

  3. Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis

    PubMed Central

    Gartlehner, Gerald; Gaynes, Bradley N; Forneris, Catherine; Asher, Gary N; Morgan, Laura C; Coker-Schwimmer, Emmanuel; Boland, Erin; Lux, Linda J; Gaylord, Susan; Bann, Carla; Pierl, Christiane Barbara; Lohr, Kathleen N

    2015-01-01

    Study question What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults? Methods This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT. Summary answer and limitations Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, −0.38, −2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of

  4. 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

  5. Antidepressant-like cognitive and behavioral effects of acute ketamine administration associated with plasticity in the ventral hippocampus to medial prefrontal cortex pathway

    PubMed Central

    Jett, Julianne D.; Boley, Angela M.; Girotti, Milena; Shah, Amiksha; Lodge, Daniel J.; Morilak, David A.

    2015-01-01

    Rationale Acute low-dose administration of the NMDA receptor antagonist, ketamine, produces rapid and sustained antidepressant-like effects in humans and rodents. Recently, we found that the long-lasting effect of ketamine on the forced swim test requires ventral hippocampal (vHipp) activity at the time of drug administration. The medial prefrontal cortex (mPFC), a target of the vHipp dysregulated in depression, is important for cognitive flexibility and response strategy selection. Deficits in cognitive flexibility, the ability to modify thoughts and behaviors in response to changes in the environment, are associated with depression. We have shown that chronic stress impairs cognitive flexibility on the attentional set-shifting test (AST), and induces a shift from active to passive response strategies on the shock-probe defensive burying test (SPDB). Objective In this study, we tested the effects of ketamine on chronic stress-induced changes in cognitive flexibility and coping behavior on the AST and SPDB, respectively. Subsequently, we investigated vHipp-mPFC plasticity as a potential mechanism of ketamine’s therapeutic action. Results Ketamine reversed deficits in cognitive flexibility and restored active coping behavior in chronically stressed rats. Further, high frequency stimulation in the vHipp replicated ketamine’s antidepressant-like effects on the forced swim test and AST, but not on the SPDB. Conclusion These results show that ketamine restores cognitive flexibility and coping response strategy compromised by stress. Activity in the vHipp-mPFC pathway may represent a neural substrate for some of the antidepressant-like behavioral effects of ketamine, including cognitive flexibility, but other circuits may mediate the effects of ketamine on coping response strategy. PMID:25986748

  6. Treatment of human aggression with major tranquilizers, antidepressants, and newer psychotropic drugs.

    PubMed

    Itil, T M; Wadud, A

    1975-02-01

    Most of the drugs used in the treatment of aggressive syndromes have originally been developed for other clinical applications. Despite significant differences in the pathogenesis of various aggressive disorders, the frequently used "antiaggression" drugs are the major tranquilizers (neuroleptics). If the aggresstion is associated with psychosis, chlorpromazine or haloperidol are the drugs of choice. Aggressive disorders within the acute and chronic brain syndromes are best treated with pericyazine, thioridazine, and thiothixene. In aggressive symptoms of mentally retarded patients, particularly with epileptic syndromes, a new benzazepine (SCH12,679)was found to be very effective. Aggression associated with alcoholism or narcotic addiction showed best response to chlorpormazine and haloperidol. As a general rule, in aggressive patients with clinically known epilepsy, or with abnormal electroencephalographic findings, the major tranquilizers with potent sedative properties should be given with great caution.

  7. 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

  8. Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction.

    PubMed

    Godsil, B P; Bontempi, B; Mailliet, F; Delagrange, P; Spedding, M; Jay, T M

    2015-11-01

    Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug's acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine's clinical efficacy, as well as its potential influence on CEA-based learning mechanisms. PMID:25560759

  9. Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction.

    PubMed

    Godsil, B P; Bontempi, B; Mailliet, F; Delagrange, P; Spedding, M; Jay, T M

    2015-11-01

    Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug's acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine's clinical efficacy, as well as its potential influence on CEA-based learning mechanisms.

  10. Burnout as a risk factor for antidepressant treatment - a repeated measures time-to-event analysis of 2936 Danish human service workers.

    PubMed

    Madsen, Ida E H; Lange, Theis; Borritz, Marianne; Rugulies, Reiner

    2015-06-01

    Burnout is a state of emotional exhaustion, feelings of reduced personal accomplishment, and withdrawal from work thought to occur as a consequence of prolonged occupational stress. The condition is not included in the diagnostic classifications, but is considered likely to develop into depressive disorder in some cases. We examined the prospective association between burnout and antidepressant treatment, as an indicator of clinically significant mental disorder. We further investigated potential effect-modifiers of the association, to identify factors that may prevent this progression of burnout. We used questionnaire data from a three-wave study of Danish human service workers conducted during 1999-2005, linked with national register data on purchases of antidepressants (ATC: N06A). We included 4788 observations from 2936 individuals (81% women) and analysed data by Aalens additive hazards modeling, examining the risk of entering antidepressant treatment in relation to the level of work-related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers we examined both sociodemographic factors and a range of psychosocial work environment factors. The level of burnout predicted antidepressant treatment. This association was modified by sex (p < 0.01). In men, high vs. intermediate burnout was associated with a 5% increased risk of antidepressant treatment per year of follow-up. This risk difference was 1% for women. Due to the sex specific patterns, we restricted effect modification analyses to women. We found no effect-modification by the examined work environment factors, though a sensitivity analysis indicated a possible stronger association in women of lower occupational position. In conclusion, burnout predicted antidepressant treatment, with a stronger association in men than women. We found no evidence of effect-modification by any of the examined psychosocial work environment factors. PMID:25943951

  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. Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, β-catenin and antidepressant-like effects

    PubMed Central

    Pilar-Cuéllar, F; Vidal, R; Pazos, A

    2012-01-01

    BACKGROUND AND PURPOSE 5-HT2A receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically. EXPERIMENTAL APPROACH Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2′-deoxyuridine (BrdU) incorporation, and β-catenin protein expression in different cellular fractions, as well as 5-HT1A receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy. KEY RESULTS mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of β-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT1A receptor function in any of the groups studied. CONCLUSIONS AND IMPLICATIONS The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT2A receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated β-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT1A receptor desensitization in the dorsal raphe nucleus. PMID:21627639

  13. [SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

    PubMed

    Shepehtko, E N; Garmash, D A; Kurbanov, A K; Marchenko, V O; Kozak, Yu S

    2016-04-01

    Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection. PMID:27434952

  14. Tissue-specific bioconcentration of antidepressants in fish exposed to effluent from a municipal sewage treatment plant.

    PubMed

    Grabicova, Katerina; Lindberg, Richard H; Ostman, Marcus; Grabic, Roman; Randak, Tomas; Larsson, D G Joakim; Fick, Jerker

    2014-08-01

    Tissue-specific bioconcentration of selected antidepressants was studied in rainbow trout (Oncorhynchus mykiss) exposed to undiluted effluent from a Swedish municipal sewage treatment plant for 13 days. Citalopram, sertraline and venlafaxine were found in the brains and livers of most fish, but not in blood plasma or muscle. Venlafaxine was the only drug found in plasma (3/20 fish). Fluoxetine was not detected in any fish tissue, in accordance with a low concentration in the effluent and a comparably high limit of quantification in tissues. Concentrations of citalopram, sertraline and venlafaxine in fish brain were up to 1/12, 1/8 and 1/26, respectively, of the lowest concentrations found in the brains of mammals treated with therapeutic doses. Thus, given co-exposure to several antidepressants and an assumed similar potency in fish, the margin of safety for target-related effects in fish residing in effluent-dominated streams is relatively low. Furthermore, the non-detectable levels of these drugs in blood plasma suggest that analyses of concentrations in target tissues (brain) would be more informative in field studies and other studies with environmentally realistic exposure concentrations. PMID:24814035

  15. Successful treatment of six patients with neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure.

    PubMed

    Sanai, Toru; Matsui, Rei; Hirano, Tadashi; Torichigai, Shinichi; Yotsueda, Hideki; Higashi, Harumichi; Hirakata, Hideki; Iida, Mitsuo

    2006-01-01

    Neuroleptic malignant syndrome is a rare but potentially lethal, rare reaction to neuroleptics which is characterized by altered levels of consciousness, extrapyramidal effects, autonomic instability, hyperthermia, and elevated serum creatine phosphokinase levels. The most serious complication of neuroleptic malignant syndrome is acute renal failure. We investigated six cases of neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure due to rhabdomyolysis and effect of hemodialysis or hemodiafiltration. The patients were five males and one female with a mean age of 43.5 yr. All of the patients, who developed acute renal failure induced from rhabdomyolysis, had previously received butyrophenone (haloperidol), phenothiazine, benzamide, iminomide, benzisoxazole, antidepressants, and hypnotics (benzodiazepine and barbiturate) for the treatment of schizophrenia. The clinical manifestations of neuroleptic malignant syndrome were characterized by altered consciousness, muscle rigidity and weakness, fever, and excessive perspiration. The peak laboratory data were blood urea nitrogen 102 +/- 26 (mean +/- SD) mg/dL, serum creatinine 9.1 +/- 2.1 mg/dL, serum creatine phosphokinase 229,720 +/- 289,940 IU/L, and all of them developed oliguric acute renal failure. Dantrolene sodium administration was given to five cases and hemodialysis or hemodiafiltration was performed in all of them. The serum creatinine level after hemodialysis or hemodiafiltration was 1.4 +/- 1.0 mg/dL. All patients were successfully cured of acute renal failure by hemodialysis or hemodiafiltration. As a result, myoglobulinemic acute renal failure associated with neuroleptic malignant syndrome was successfully treated by hemodialysis or hemodiafiltration.

  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. 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

  18. 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.

  19. Acute withdrawal: diagnosis and treatment.

    PubMed

    Brust, John C M

    2014-01-01

    Symptoms of alcohol withdrawal range in severity from mild "hangover" to fatal delirium tremens (DTs). Tremor, hallucinosis, and seizures usually occur within 48 hours of abstinence. Seizures tend to be generalized without focality, occurring singly or in a brief cluster, but status epilepticus is not unusual. DTs usually appears after 48 hours of abstinence and consists of marked inattentiveness, agitation, hallucinations, fluctuating level of alertness, marked tremulousness, and sympathetic overactivity. The mainstay of treatment for alcohol withdrawal is benzodiazepine pharmacotherapy, which can be used to control mild early symptoms, to prevent progression to DTs, or to treat DTs itself. Alternative less evidence-based pharmacotherapies include phenobarbital, anticonvulsants, baclofen, gamma-hydroxybutyric acid, beta-blockers, alpha-2-agonists, and N-methyl-d-aspartate receptor blockers. Treatment of DTs is a medical emergency requiring heavy sedation in an intensive care unit, with close attention to autonomic instability, fever, fluid loss, and electrolyte imbalance. Frequent comorbid disorders include hypoglycemia, liver failure, pancreatitis, sepsis, meningitis, intracranial hemorrhage, and Wernicke-Korsakoff syndrome.

  20. The influence of patients' attributions of the immediate effects of treatment of depression on long-term effectiveness of behavioural activation and antidepressant medication.

    PubMed

    Moradveisi, Latif; Huibers, Marcus J H; Arntz, Arnoud

    2015-06-01

    Patients' attributions of effects of treatment are important, as these can affect long-term outcome. Most studies so far focused on the influence of attributions to medication for anxiety and depression disorders. We investigated the effects of patients' attributions made after acute treatment on the long-term outcome of antidepressant medication (ADM) and psychological treatment (behavioural activation, BA). Data are based on a randomized trial testing the effectiveness of BA vs. ADM for major depression (MDD) in Iran. Patients with MDD (N = 100) were randomized to BA (N = 50) or ADM (N = 50). Patients' attributions were assessed at post-test (after completion of the treatments). Scores on an attribution questionnaire were factor analysed, and factor scores were retained as predictors of depressive symptoms at 1-year follow-up. Regression analysis was used to test whether attributions predicted depressive symptoms at 1-yr follow-up, controlling for symptom level, condition, and their interaction at post-test. Belief in coping efficacy was the only attribution factor significantly predicting 1-year HRSD scores, controlling for condition, post-test HRSD and their interaction. It also mediated the condition differences at follow-up. Credit to self was the single attribution factor that predicted BDI follow-up scores, controlling for condition, posttest BDI, and their interaction. It partially mediated the condition differences on the BDI at follow-up. Attribution to increased coping capacities and giving credit to self appear essential. In the long-term (at 1 year follow-up), the difference in outcome between BA and ADM (with BA being superior to ADM) is at least partially mediated by attributions.

  1. 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

  2. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for acute myeloid leukemia What’s new in acute myeloid leukemia research and treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  3. Microbiology and Treatment of Acute Apical Abscesses

    PubMed Central

    Rôças, Isabela N.

    2013-01-01

    SUMMARY Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease. PMID:23554416

  4. Preferential reduction of binding of sup 125 I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments

    SciTech Connect

    Ordway, G.A.; Gambarana, C.; Tejani-Butt, S.M.; Areso, P.; Hauptmann, M.; Frazer, A. )

    1991-05-01

    This study utilized quantitative receptor autoradiography to examine the effects of repeated administration of antidepressants to rats on the binding of the beta adrenoceptor antagonist, {sup 125}I-iodopindolol ({sup 125}I-IPIN) to either beta-1 or beta-2 adrenoceptors in various regions of brain. Antidepressants were selected to represent various chemical and pharmacological classes including tricyclic compounds (desipramine and protriptyline), monoamine oxidase inhibitors (clorgyline, phenelzine and tranylcypromine), atypical antidepressants (mianserin and trazodone) and selective inhibitors of the uptake of serotonin (citalopram and sertraline). Additionally, rats were treated with various psychotropic drugs that lack antidepressant efficacy (cocaine, deprenyl, diazepam and haloperidol). Repeated treatment of rats with desipramine, protriptyline, clorgyline, phenelzine, tranylcypromine or mianserin reduced the binding of {sup 125}I-IPIN to beta-1 adrenoceptors in many brain areas. Only in the basolateral and lateral nuclei of the amygdala did all six of these antidepressants significantly reduce {sup 125}I-IPIN binding to beta-1 adrenoceptors. In these amygdaloid nuclei, the magnitude of the reduction in the binding of {sup 125}I-IPIN caused by each of these drugs was comparable to or greater than the reduction in binding produced in any other region of brain. Reductions of binding of {sup 125}I-IPIN after antidepressant treatments were not consistently observed in the cortex, the area of brain examined most often in homogenate binding studies. Only the monoamine oxidase inhibitors caused reductions in the binding of {sup 125}I-IPIN to beta-2 adrenoceptors, and this effect was generally localized to the amygdala and hypothalamus.

  5. 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

  6. [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.

  7. Mood regulation. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment.

    PubMed

    Shabel, Steven J; Proulx, Christophe D; Piriz, Joaquin; Malinow, Roberto

    2014-09-19

    The lateral habenula (LHb), a key regulator of monoaminergic brain regions, is activated by negatively valenced events. Its hyperactivity is associated with depression. Although enhanced excitatory input to the LHb has been linked to depression, little is known about inhibitory transmission. We discovered that γ-aminobutyric acid (GABA) is co-released with its functional opponent, glutamate, from long-range basal ganglia inputs (which signal negative events) to limit LHb activity in rodents. At this synapse, the balance of GABA/glutamate signaling is shifted toward reduced GABA in a model of depression and increased GABA by antidepressant treatment. GABA and glutamate co-release therefore controls LHb activity, and regulation of this form of transmission may be important for determining the effect of negative life events on mood and behavior.

  8. Seasonal changes in antibiotics, antidepressants/psychiatric drugs, antihistamines and lipid regulators in a wastewater treatment plant.

    PubMed

    Golovko, Oksana; Kumar, Vimal; Fedorova, Ganna; Randak, Tomas; Grabic, Roman

    2014-09-01

    Seasonal changes in the concentration of 21 pharmaceuticals in a wastewater treatment plant (WWTP) in České Budějovice were investigated over 12months. The target compounds were 10 antibiotics, 4 antidepressants, 3 psychiatric drugs, 2 antihistamines and 2 lipid regulators. 272 Wastewater samples (136 influents and 136 effluents) were collected from March 2011 to February 2012 and analyzed using two-dimensional liquid chromatography coupled with tandem mass spectrometry. All studied pharmaceuticals were frequently detected in both the influent and the effluent wastewater samples, except for meclozine, which was only found in the influent. The mean concentration of pharmaceuticals varied from 0.006μgL(-1) to 1.48μgL(-1) in the influent and from 0.003μgL(-1) to 0.93μgL(-1) in the effluent. The concentration of most pharmaceuticals was higher during winter. PMID:24997947

  9. Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder

    PubMed Central

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R. Bruce; Walling, David; Schooler, Nina; Lindenmayer, Jean-Pierre; Canuso, Carla; Alphs, Larry

    2016-01-01

    Abstract The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subjects with acute exacerbation of SCA (ie, with psychotic and either depressive and/or manic symptoms) were enrolled and treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers (combination therapy group). After flexible-dose treatment with PP1M for 13 weeks, stabilized subjects continued into a 12-week fixed-dose PP1M treatment period. A total of 667 subjects were enrolled; 320 received monotherapy and 347 received PP1M as combination therapy; 334 subjects completed the entire 25-week treatment. Statistically significant and clinically meaningful improvements from baseline were observed for all efficacy measures in psychosis (per Positive and Negative Syndrome Scale), mood symptoms (per Young Mania Rating Scale and Hamilton Depression Rating Scale—21 items), and functioning (per Personal and Social Performance Scale) from week 1 to all time points during the 25-week treatment period (P < 0.001). Similar improvements in efficacy measures were observed between subjects receiving monotherapy or combination therapy. Efficacy benefits persisted throughout the 25-week period. The most common adverse events were akathisia (11.1%), injection-site pain (10.6%), and insomnia (10.0%). Paliperidone palmitate once-monthly administered as monotherapy or in combination with mood stabilizers or antidepressants in patients with an acute exacerbation of SCA provided rapid, broad, and persistent reduction in psychotic, depressive, and manic symptoms, as well as improved functioning. PMID:27322760

  10. Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder.

    PubMed

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R Bruce; Walling, David; Schooler, Nina; Lindenmayer, Jean-Pierre; Canuso, Carla; Alphs, Larry

    2016-08-01

    The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subjects with acute exacerbation of SCA (ie, with psychotic and either depressive and/or manic symptoms) were enrolled and treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers (combination therapy group). After flexible-dose treatment with PP1M for 13 weeks, stabilized subjects continued into a 12-week fixed-dose PP1M treatment period. A total of 667 subjects were enrolled; 320 received monotherapy and 347 received PP1M as combination therapy; 334 subjects completed the entire 25-week treatment. Statistically significant and clinically meaningful improvements from baseline were observed for all efficacy measures in psychosis (per Positive and Negative Syndrome Scale), mood symptoms (per Young Mania Rating Scale and Hamilton Depression Rating Scale-21 items), and functioning (per Personal and Social Performance Scale) from week 1 to all time points during the 25-week treatment period (P < 0.001). Similar improvements in efficacy measures were observed between subjects receiving monotherapy or combination therapy. Efficacy benefits persisted throughout the 25-week period. The most common adverse events were akathisia (11.1%), injection-site pain (10.6%), and insomnia (10.0%). Paliperidone palmitate once-monthly administered as monotherapy or in combination with mood stabilizers or antidepressants in patients with an acute exacerbation of SCA provided rapid, broad, and persistent reduction in psychotic, depressive, and manic symptoms, as well as improved functioning. PMID:27322760

  11. Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV.

    PubMed

    Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

    2016-01-01

    Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0-2 months), young adult (2-4 months), and old adult (12-14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults. PMID:27648918

  12. Region-dependent and stage-specific effects of stress, environmental enrichment, and antidepressant treatment on hippocampal neurogenesis.

    PubMed

    Tanti, Arnaud; Westphal, Willy-Paul; Girault, Virginie; Brizard, Bruno; Devers, Severine; Leguisquet, Anne-Marie; Surget, Alexandre; Belzung, Catherine

    2013-09-01

    Chronic stress and depression are associated with decreased levels of hippocampal neurogenesis. On the other hand, antidepressants as well as environmental enrichment may rely in part on their pro-neurogenic effects to improve cognition and mood. Because a functional heterogeneity has been consistently reported along the septo-temporal axis of the hippocampus, regional changes in neurogenesis could differentially contribute to these effects and affect distinct hippocampal functions. Mapping these regional changes could therefore provide a better understanding of the function of newborn neurons. While some studies report region-specific effects of stress and antidepressants on neurogenesis, it is unclear whether these changes affect distinct populations of newborn neurons according to their developmental stage in a region-specific manner. By using endogenous markers and BrdU labeling we quantified the regional changes in cell proliferation and survival as well as in the number of neuronal progenitors and immature neurons following unpredictable chronic mild stress (UCMS), environmental enrichment (EE) and chronic fluoxetine (20 mg/kg/day) treatment along the septo-temporal axis of the hippocampus. EE promoted cell proliferation and survival of 4-week-old newborn cells as well as increased the number and proportion of post-mitotic immature neurons specifically within the septal hippocampus. By contrast, UCMS uniformly decreased cell proliferation, survival and immature newborn neurons but differentially affected progenitor cells with a decrease restricted to the temporal regions of the hippocampus. Whereas fluoxetine treatment in control mice affected proliferation and survival specifically in the temporal hippocampus, it reversed most of the UCMS-induced alterations all along the septo-temporal axis. These results highlight that different factors known for exerting a mood improving effect differentially regulate neurogenesis along the septo-temporal axis of the

  13. Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV.

    PubMed

    Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

    2016-09-20

    Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0-2 months), young adult (2-4 months), and old adult (12-14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults.

  14. Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV

    PubMed Central

    Jha, S; Dong, B E; Xue, Y; Delotterie, D F; Vail, M G; Sakata, K

    2016-01-01

    Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0–2 months), young adult (2–4 months), and old adult (12–14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults. PMID:27648918

  15. [Incidence and therapeutic relevance of the adverse effects of antidepressive agents within the scope of ambulatory neurologic treatment].

    PubMed

    Schmidt, L G; Schüssler, G; Linden, M; Müller-Oerlinghausen, B

    1988-04-01

    Within a postmarketing drug surveillance study the incidence and relevance of ADRs leading to drug discontinuation in therapy of depressed outpatients were examined. In addition, corresponding drug prescribing patterns of patients under routine treatment conditions were recorded. It was found that most psychiatric outpatients were able to identify common ADRs and to differentiate them from the underlying illnesses and comedication. Low-dose therapy was confirmed as routine treatment in the majority of psychiatric outpatients. No differences regarding age, sex, and dosage could be found between patients with further drug intake and those who stopped their antidepressant medication because of ADRs. Such events had been recorded in 11.5% of patients with first prescriptions made by the treating physicians in a monitoring of three months. However, only 0.3% of patients on long-term therapy (that had been initiated at treatment terms preceding the monitoring period) experienced an ADR indicating a decreased risk for drug discontinuation (because of ADR) the longer the patient was on treatment. Knowing ADR(-profiles) of prescribed drugs by treating psychiatrist may aid the treatment of compliance or prevention of ADRs. PMID:3384381

  16. 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

  17. Depressed College Students and Tricyclic Antidepressant Therapy.

    ERIC Educational Resources Information Center

    Brown, Ben Maurice

    1978-01-01

    Depressed college students representing several distinct diagnostic groups were studied. Evidence indicates that patients with depressive neurosis show optimal treatment outcomes following tricyclic antidepressant therapy. (JMF)

  18. 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

  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. Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study.

    PubMed

    Perlis, Roy H; Moorjani, Priya; Fagerness, Jesen; Purcell, Shaun; Trivedi, Madhukar H; Fava, Maurizio; Rush, A John; Smoller, Jordan W

    2008-11-01

    Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (KCNK2 (TREK1), SLC18A2 (VMAT2), S100A10, and HDAC5) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C(16)) score < or =5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in KCNK2 were associated with treatment response (Bonferroni-corrected, gene-based empirical p<0.001). In follow-up analyses, KCNK2 was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (n=225). These findings indicate that genetic variation in KCNK2 may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.

  1. Biochemical profile in patients with anxious depression under the treatment with serotonergic antidepressants with different mechanisms of action.

    PubMed

    Uzbekov, Marat G; Misionzhnik, Eduard Y; Maximova, Natella M; Vertogradova, Olga P

    2006-03-01

    The pharmacodynamics of serotonergic antidepressants that differentially influence serotonin reuptake transporters is poorly investigated. The aim of this study was to compare the biochemical profiles in patients with anxious depression under the treatment with tianeptine, a serotonin reuptake enhancer, and sertraline, a selective serotonin reuptake inhibitor. Platelet monoamine oxidase (MAO) and serum amine oxidase (AO) activities, concentration of middle-mass endotoxic molecules (MMEM) and parameters that characterize the functional properties of serum albumin were investigated in 43 patients with anxious depression (ICD-10: F 32.1 and F 33.1). It was established that, in comparison with healthy controls, patients with anxious depression were characterized by the significant increase in MAO activity (by 95%), MMEM concentration (by 86%), and a significant decrease in AO activity (by 43%) and also in functional albumin activity. The results of the study show that both tianeptine and sertraline are equally effective in the treatment of anxious depression. The present biochemical investigation, however, suggests that the underlying biochemical changes are more complete following tianeptine treatment.

  2. Long-term voluntary exercise and the mouse hypothalamic-pituitary-adrenocortical axis: impact of concurrent treatment with the antidepressant drug tianeptine.

    PubMed

    Droste, S K; Schweizer, M C; Ulbricht, S; Reul, J M H M

    2006-12-01

    We investigated whether voluntary exercise and concurrent antidepressant treatment (tianeptine; 20 mg/kg/day; 4 weeks) exert synergistic effects on the mouse hypothalamic-pituitary-adrenocortical (HPA) axis. Animals had access to a running wheel, were treated with the antidepressant, or received both conditions combined. Control mice received no running wheel and no drug treatment. Exercise resulted in asymmetric changes in the adrenal glands. Whereas sedentary mice had larger left adrenals than right ones, this situation was abolished in exercising animals, mainly due to enlargement of the right adrenal cortex. However, antidepressant treatment alone was ineffective whereas the combination of antidepressant treatment and exercise resulted in an enlargement of both adrenal cortices. In these respective conditions, the levels of tyrosine hydroxylase (TH) mRNA expression in the left and right adrenal medullas varied greatly in parallel to the changes observed in the adrenal cortex sizes. TH mRNA expression in the locus coeruleus of exercising mice was significantly increased irrespective of concomitant tianeptine treatment. Corticotrophin-releasing factor mRNA levels in the hypothalamic paraventricular nucleus were decreased after voluntary exercise but were unaffected by tianeptine. Exercise, particularly in combination with tianeptine treatment, resulted in decreased early morning baseline plasma levels of corticosterone. If animals were exposed to novelty (i.e. a mild psychological stressor), a decreased response in plasma corticosterone levels was observed in the exercising mice. By contrast, after restraint, a mixed physical and psychological stressor, exercising mice showed an enhanced response in plasma corticosterone compared to the controls; a response which was even further boosted in exercising mice concomitantly treated with tianeptine. Under either condition, plasma adrenocorticotrophic hormone levels were not different between groups. Thus, voluntary

  3. Functional Dyspepsia Treatment Trial (FDTT): A double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics

    PubMed Central

    Talley, Nicholas J.; Locke, G. Richard; Herrick, Linda M.; Silvernail, Vickie M.; Prather, Charlene M.; Lacy, Brian E.; DiBaise, John K.; Howden, Colin W.; Brenner, Darren M.; Bouras, Ernest P.; El-Serag, Hashem B.; Abraham, Bincy P.; Moayyedi, Paul; Zinsmeister, Alan R.

    2014-01-01

    Background Functional dyspepsia (FD) is a common problem affecting up to 10–25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. Objectives The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. Design The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNβ3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. Methods The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651). PMID:22343090

  4. Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial

    PubMed Central

    El-Mallakh, Rif S.; Vöhringer, Paul A.; Ostacher, Michael M.; Baldassano, Claudia F.; Holtzman, Niki S.; Whitham, Elizabeth A.; Thommi, Sairah B.; Goodwin, Frederick K.; Ghaemi, S. Nassir

    2015-01-01

    Background The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic. Methods As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue versus discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers. Results In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs NRC was 0.85 ± 0.37 (SE), df=28, p =0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals [9.9%, 46.5%], p = 0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size. Conclusions In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, versus antidepressant discontinuation. PMID:26142612

  5. Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients.

    PubMed

    Rzezniczek, S; Obuchowicz, M; Datka, W; Siwek, M; Dudek, D; Kmiotek, K; Oved, K; Shomron, N; Gurwitz, D; Pilc, A

    2016-01-01

    Major depression disorder (MDD) is the most widespread mental disorder. Selective serotonin reuptake inhibitors (SSRIs) are used as first-line MDD treatment but are effective in <70% of patients. Thus, biomarkers for the early identification of treatment-resistant (TR) MDD patients are needed for prioritizing them for alternative therapeutics. SSRI-induced inhibition of the growth of peripheral blood mononuclear cells (PBMCs) is mediated via their target, the serotonin transporter (SERT). Here, we examined whether antidepressant drug-induced inhibition of the growth of PBMCs differed between MDD patients and healthy controls. PBMCs from well-characterized 33 treatment-sensitive (TS) and 33 TR MDD patients, and 24 healthy volunteers were studied. Dose-dependent inhibition of PBMCs growth was observed for both the non-SSRI antidepressant mirtazapine and the SSRI antidepressant paroxetine. Significantly lower sensitivities to 20 μm paroxetine were observed in MDD compared with control PBMCs prior to treatment onset (13% and 46%, respectively; P<0.05). Following antidepressant drug treatment for 4 or 7 weeks, the ex vivo paroxetine sensitivity increased to control levels in PBMCs from TS but not from TR MDD patients. This suggests that the low ex vivo paroxetine sensitivity phenotype reflects a state marker of depression. A significantly lower expression of integrin beta-3 (ITGB3), a co-factor of the SERT, was observed in the PBMCs of MDD patients prior to treatment onset compared with healthy controls, and may explain their lower paroxetine sensitivity. Further studies with larger cohorts are required for clarifying the potential of reduced PBMCs paroxetine sensitivity and lower ITGB3 expression as MDD biomarkers. PMID:27244236

  6. Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants: A Meta-Analysis Following the PRISMA Guidelines.

    PubMed

    Li, Dian-Jeng; Tseng, Ping-Tao; Chen, Yen-Wen; Wu, Ching-Kuan; Lin, Pao-Yen

    2016-03-01

    Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P < 0.001), and the treatment effect was similar to other antidepressants/standard treatments (P = 0.220). There were no significant differences in the dropout rate (P = 0.285) and rate of phase shifting (P = 0.952) between BD patients who received bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other antidepressants as

  7. Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants: A Meta-Analysis Following the PRISMA Guidelines.

    PubMed

    Li, Dian-Jeng; Tseng, Ping-Tao; Chen, Yen-Wen; Wu, Ching-Kuan; Lin, Pao-Yen

    2016-03-01

    Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P < 0.001), and the treatment effect was similar to other antidepressants/standard treatments (P = 0.220). There were no significant differences in the dropout rate (P = 0.285) and rate of phase shifting (P = 0.952) between BD patients who received bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other antidepressants as

  8. [Differentiated treatment of acute diffuse brain injuries].

    PubMed

    Pedachenko, E G; Dziak, L A; Sirko, A G

    2012-01-01

    Diagnosis and treatment results of 57 patients with acute diffuse brain injury have been analyzed. Patients were divided into two groups: first study period 2000-2005; second study period 2006-2010. The main differences between the first and the second study periods were in health condition and brain functions monitoring parameters, therapy approaches and goals. Increasing of axial and lateral dislocation symptoms during progression from the first type of diffuse injury to the fourth one is related to intracranial hypertension (ICH) occurrence rate and significance it's significance. During the second study period, ICH was found in 25% patients with the second type of injury, 57% patients with the third type of injury, and 80%, with the fourth type of injury. Mean ICP in the group of patients with the second type of diffuse injury comprised 14.4 +/- 6.6 mmHg; with the third type of injury, 30 +/- 20.6 mmHg; with the fourth type of injuty, 37.6 +/- 14.1 mmHg. Introduction of differentiated approach to conservative or surgical treatment method application to acute diffuse brain injuries patients based on ICP monitoring data led to 13.8% reduction in mortality in the second study period compared with the first study period.

  9. Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment.

    PubMed

    Heller, Aaron S; Johnstone, Tom; Light, Sharee N; Peterson, Michael J; Kolden, Gregory G; Kalin, Ned H; Davidson, Richard J

    2013-02-01

    OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.

  10. Use of antidepressants in the treatment of major depressive disorder in primary care during a period of economic crisis

    PubMed Central

    Sicras-Mainar, Antoni; Navarro-Artieda, Ruth

    2016-01-01

    Objective To describe antidepressant (AD) use in the treatment of major depressive disorder during a period of economic crisis. Patients and methods This was a retrospective, observational study using population-based databases. Two periods were considered: 1) 2008–2009, precrisis, and 2) 2012–2013, economic crisis. Certain inclusion/exclusion criteria were taken into account for the study (initiation of AD treatment). Patients were followed up for 12 months. The main measures were use (defined daily doses), epidemiologic measures, strategies used and treatment persistence, referrals, and use of resources. Statistical significance was set at P<0.05. Results In the precrisis period, 3,662 patients were enrolled, and 5,722 were enrolled in the period of economic crisis. Average age was 58.8 years and 65.4% were women. Comparing the two periods, major depressive disorder prevalence was 5.4% vs 8.1%, P<0.001. During the period of economic crisis, AD use rose by 35.2% and drug expenditures decreased by 38.7%. Defined daily dose per patient per day was 10.0 mg vs 13.5 mg, respectively, P<0.001. At 12-month follow-up, the majority of patients (60.8%) discontinued the treatment or continued on the same medication as before, and in 23.3% a change of AD was made. Conclusion Primary health care professionals are highly involved in the management of the illness; in addition, during the period of economic crisis, patients with major depressive disorder showed higher rates of prevalence of the illness, with increased use of AD drugs. PMID:26766910

  11. Treatment and pathogenesis of acute hyperkalemia

    PubMed Central

    Mushiyakh, Yelena; Dangaria, Harsh; Qavi, Shahbaz; Ali, Noorjahan; Pannone, John; Tompkins, David

    2012-01-01

    This article focuses on the pathogenesis, clinical manifestations, and various treatment modalities for acute hyperkalemia and presents a systematic approach to selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused by extracellular potassium shift or decreased renal potassium excretion, usually presents with non-specific symptoms. Early recognition of moderate to severe hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle paralysis. Management of hyperkalemia includes the elimination of reversible causes (diet, medications), rapidly acting therapies that shift potassium into cells and block the cardiac membrane effects of hyperkalemia, and measures to facilitate removal of potassium from the body (saline diuresis, oral binding resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L or EKG changes is a medical emergency and should be treated accordingly. Treatment should be started with calcium gluconate to stabilize cardiomyocyte membranes, followed by insulin injection, and b-agonists administration. Hemodialysis remains the most reliable method to remove potassium from the body and should be used in cases refractory to medical treatment. Prompt detection and proper treatment are crucial in preventing lethal outcomes. PMID:23882341

  12. Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial

    PubMed Central

    IJff, Marjoliek A; Huijbregts, Klaas ML; van Marwijk, Harm WJ; Beekman, Aartjan TF; Hakkaart-van Roijen, Leona; Rutten, Frans F; Unützer, Jürgen; van der Feltz-Cornelis, Christina M

    2007-01-01

    Background Depressive disorder is currently one of the most burdensome disorders worldwide. Evidence-based treatments for depressive disorder are already available, but these are used insufficiently, and with less positive results than possible. Earlier research in the USA has shown good results in the treatment of depressive disorder based on a collaborative care approach with Problem Solving Treatment and an antidepressant treatment algorithm, and research in the UK has also shown good results with Problem Solving Treatment. These treatment strategies may also work very well in the Netherlands too, even though health care systems differ between countries. Methods/design This study is a two-armed randomised clinical trial, with randomization on patient-level. The aim of the trial is to evaluate the treatment of depressive disorder in primary care in the Netherlands by means of an adapted collaborative care framework, including contracting and adherence-improving strategies, combined with Problem Solving Treatment and antidepressant medication according to a treatment algorithm. Forty general practices will be randomised to either the intervention group or the control group. Included will be patients who are diagnosed with moderate to severe depression, based on DSM-IV criteria, and stratified according to comorbid chronic physical illness. Patients in the intervention group will receive treatment based on the collaborative care approach, and patients in the control group will receive care as usual. Baseline measurements and follow up measures (3, 6, 9 and 12 months) are assessed using questionnaires and an interview. The primary outcome measure is severity of depressive symptoms, according to the PHQ9. Secondary outcome measures are remission as measured with the PHQ9 and the IDS-SR, and cost-effectiveness measured with the TiC-P, the EQ-5D and the SF-36. Discussion In this study, an American model to enhance care for patients with a depressive disorder, the

  13. A role for galanin in antidepressant actions with a focus on the dorsal raphe nucleus

    PubMed Central

    Lu, Xiaoying; Barr, Alasdair M.; Kinney, Jefferson W.; Sanna, Pietro; Conti, Bruno; Behrens, M. Margarita; Bartfai, Tamas

    2005-01-01

    Selective serotonin reuptake inhibitors, such as fluoxetine (FLX), are the most commonly used drugs in the treatment of major depression. However, there is a limited understanding of their molecular mechanism of action. Although the acute effect of selective serotonin reuptake inhibitors in elevating synaptic serotonin concentrations is well known, the clinical amelioration of depressive symptoms requires 14-21 days of treatment, suggesting that numerous other rearrangements of function in the CNS must take place. In the present study, we demonstrated that 14 days of FLX treatment up-regulated galanin mRNA levels by 100% and GalR2-binding sites by 50%, in the rat dorsal raphe nucleus, where galanin coexists with serotonin. Furthermore, a galanin receptor antagonist, M40, attenuated the antidepressant-like effect of FLX in the forced swim test, a rodent preclinical screen commonly used to evaluate antidepressant-like efficacy. Direct activation of galanin receptors by a galanin receptor agonist, galnon, was found to produce an antidepressant-like effect in the same task. Two other antidepressant treatments also affected the galaninergic system in the monoaminergic nuclei: Electroconvulsive shock elevated galanin mRNA levels in dorsal raphe nucleus, whereas sleep deprivation increased galanin mRNA levels in the locus coeruleus, further underlining the connection between activation of the galaninergic system and antidepressant action of various clinically proven treatments. PMID:15647369

  14. Efficacy of Chronic Antidepressant Treatments in a New Model of Extreme Anxiety in Rats

    PubMed Central

    Javelot, Hervé; Weiner, Luisa; Terramorsi, Roxane; Rougeot, Catherine; Lalonde, Robert; Messaoudi, Michaël

    2011-01-01

    Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders. PMID:21808731

  15. Relationship Between Depressive State and Treatment Characteristics of Acute Cervical Spinal Cord Injury in Japan

    PubMed Central

    Matsuda, Yasufumi; Kubo, Tatsuhiko; Fujino, Yoshihisa; Matsuda, Shinya; Wada, Futoshi; Sugita, Atsuko

    2016-01-01

    Background Few studies have assessed whether treatment of acute cervical spinal cord injury (SCI) patients contributes to depression. Methods Using an administrative database, we assessed patients for whom the diagnosis was unspecified injuries of cervical spinal cord (International Classification of Diseases and Injuries-10th (ICD-10) code; S14.1). We categorized patients with codes for depressive episode (ICD-10 code; F32) or recurrent depressive disorder (F33), or those prescribed antidepressants (tricyclic, tetracyclic, Selective Serotonin Reuptake Inhibitors, Serotonin Noradrenaline Reuptake Inhibitors, Trazodone, Sulpiride, or Mirtazapine) as having a depressive state. We compared the rate of each acute treatment between the depressive state group and the non-depressive state group using chi-square tests, and a multiple logistic regression model was used to identify the association between the acute treatment and depressive state. Results There were 151 patients who were judged to be in a depressive state, and the other 2115 patients were categorized into the non-depressive state group. Intervention of intravenous anesthesia, tracheostomy, artificial respiration, and gastrostomy had a significant positive correlation with depressive state. Multiple logistic regression analysis showed that tracheostomy (odds ratio [OR] 2.18; 95% confidence interval [CI], 1.09–4.38) and artificial respiration (OR 2.28; 95% CI, 1.32–3.93) were significantly associated with depressive state, and men had a 36% reduction in the risk of depressive state compared with women (OR 0.64; 95% CI, 0.44–0.94), whereas age, wound-treatment, all of the orthopedic procedures, intravenous anesthesia, and gastrostomy were not associated with depressive state. Conclusions These findings suggest that tracheostomy, artificial respiration and female gender in the acute phase after cervical SCI might be associated with the development of depression. PMID:26567604

  16. Acute migraine: Current treatment and emerging therapies

    PubMed Central

    Kalra, Arun A; Elliott, Debra

    2007-01-01

    Migraine is a common disabling primary headache disorder. Despite the need for a perfect treatment of this debilitating condition, the ideal “cure” eludes us. In 1992, the first triptan was released in the US for use in acute migraine. Triptans are more specific for the serotonin receptor 5-hydroxy triptamine (5-HT) 1 than previously prescribed drugs, such as ergotamines, with fewer side effects. This was an important first step in specific acute migraine therapy. Today however, triptans continue to be underutilized. There remains a concern, among practitioners and patients, about possible cardiovascular safety issues, despite the lack of strong evidence of serious adverse events. In fact, triptans now have a safe track record over more than a decade of use. Other perceived downfalls to use, include cost and variable efficacy. The more we learn about the clinical features and pathophysiology of migraine, the closer we are to finding a satisfactory monotherapy. Until then, recognizing that mixed mechanisms underlie migraine symptoms, rational polytherapy can be useful. Research on the roles of serotonin, calcitonin gene related peptide, glutamine and N-methyl-D-aspartate in the trigeminovascular system holds promise for those searching for the perfect migraine headache cure. PMID:18488069

  17. Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study.

    PubMed

    White, K; Pistole, T; Boyd, J L

    1980-11-01

    Thirty newly hospitalized patients with RDC major or minor depressive disorder were randomly assigned to open treatment according to fixed dosage steps with 1) amitriptyline alone, up to a maximum dose of 300 mg/day; 2) tranylcypromine alone, up to a maximum dose of 40 mg/day; or 3) the combination of amitriptyline, up to 150 mg/day, and tranylcypromine, up to 20 mg/day. For 28 patients this protocol continued for 4 weeks or until discharge. As measured by the Hamilton and Zung depression scales, patients in all three treatment groups improved equally. The combination treatment produced a nonsignificantly higher frequency of minor side effects, none of which required discontinuation of treatment. The results indicate the feasibility and safety of further controlled clinical research with combined treatment, although caution is advised.

  18. 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

  19. 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.

  20. Antidepressant, Antipsychotic, and Hallucinogen Drugs for the Treatment of Psychiatric Disorders: A Convergence at the Serotonin-2A Receptor.

    PubMed

    Howland, Robert H

    2016-07-01

    Antidepressant, atypical antipsychotic, and hallucinogen drugs mediate their actions in part by interactions with the serotonin-2A (5HT2A) receptor. Serotonergic hallucinogen drugs, such as psilocybin, bind most potently as agonists at the 5HT2A receptor, producing profound changes in perception, mood, and cognition. Some of these drugs have been or are currently being investigated in small Phase 2 studies for depression, alcoholism, smoking cessation, anxiety, and posttraumatic stress disorder. However, unlike the synergistic effects of combining antidepressant and atypical antipsychotic drugs, the potential therapeutic effects of hallucinogen drugs may be attenuated by the concurrent use of these medications because antidepressant and atypical antipsychotic drugs desensitize and/or down-regulate 5HT2A receptors. This finding has important implications for optimizing the potential therapeutic use of hallucinogen drugs in psychiatry. [Journal of Psychosocial Nursing and Mental Health Services, 54(7), 21-24.]. PMID:27362381

  1. 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

  2. Endovascular treatment of acute ischemic stroke.

    PubMed

    Leslie-Mazwi, Thabele; Rabinov, James; Hirsch, Joshua A

    2016-01-01

    Endovascular thrombectomy is an effective treatment for major acute ischemic stroke syndromes caused by major anterior circulation artery occlusions (commonly referred to as large vessel occlusion) and is superior to intravenous thrombolysis and medical management. Treatment should occur as quickly as is reasonably possible. All patients with moderate to severe symptoms (National Institutes of Health stroke scale >8) and a treatable occlusion should be considered. The use of neuroimaging is critical to exclude hemorrhage and large ischemic cores. Very shortly after stroke onset (<3 hours) computed tomography (CT) and CT angiography provide sufficient information to proceed; diffusion magnetic resonance imaging (MRI) is less reliable during this early stage. After 3 hours from onset diffusion MRI is the most reliable method to define ischemic core size and should be used in centers that can offer it rapidly. Recanalization is highly effective with a stentriever or using a direct aspiration technique, with the patient awake or under conscious sedation rather than general anesthesia, if it may be performed safely. After thrombectomy the patient should be admitted to an intensive care setting and inpatient rehabilitation undertaken as soon as feasible. Patient outcomes should be assessed at 3 months, preferably using the modified Rankin score. PMID:27430469

  3. Treatment of the acute traumatic acromioclavicular separation.

    PubMed

    Bishop, Julie Y; Kaeding, Christopher

    2006-12-01

    Injuries to the acromioclavicular joint occur commonly in athletes, especially those involved in contact sports. The majority of these injuries are type I and II acromioclavicular joint separations and are treated nonoperatively with rehabilitation. A rapid and full return to play is expected. Acute types IV, V, and VI are less common and operative intervention is recommended. The type III injury is more controversial and current trends are towards initial nonoperative management. Operative treatment is sought only when the athlete remains symptomatic with painful instability. However, some do support early intervention in the overhead athlete. The goal of operative intervention is to create a stiff and strong repair/reconstruction of the coracoclavicular ligaments while providing stability in all planes. This will allow early and more aggressive rehabilitation. Surgical treatment includes reconstruction of the coracoclavicular ligaments with an augmented coracoacromial ligament transfer and more recently tendon graft reconstructions. Biomechanical research supports an anatomic reconstruction of the ligaments to confer the most function and stability.

  4. Pterostilbene as treatment for severe acute pancreatitis.

    PubMed

    Lin, Y J; Ding, Y; Wu, J; Ning, B T

    2016-01-01

    Acute pancreatitis (AP) has a fast onset and progression, which lead to an unfavorable prognosis. Therefore, the development of novel drugs for its treatment is critical. As a homologous derivative of resveratrol, pterostilbene exerts a variety of effects including anti-inflammatory, antioxidant, and antitumor effects. This study investigated the potential of pterostilbene for treatment of severe AP (SAP) and related mechanisms. Effects of pterostilbene were evaluated in a Wistar rat model of AP. Serum levels of amylase (AMY), creatinine (Cr), and alanine aminotransferase (ALT) were quantified. Furthermore, serum levels of tumor necrosis factor (TNF)-a and interleukin (IL)-1b were quantified using enzyme-linked immunosorbent assay. Nuclear factor (NF)-kB expression in pancreatic tissues was quantified by real-time PCR and western blotting. The production of reactive oxygen species (ROS) was determined using a spectrometer, while superoxide dismutase (SOD) activity was assayed. In the AP rat model, the expression of inflammatory markers TNF-a and IL-1b, expression of NF-kB, and serum indices (AMY, Cr, and ALT) increased compared to the corresponding levels in the control group (P < 0.05). Pterostilbene reduced serum levels of TNF-a and IL-1b; decreased NF-kB gene expression, serum indices, and ROS generation; and increased SOD activity in a dose-dependent manner. In conclusion, pterostilbene can alleviate SAP-induced tissue damage by decreasing the inflammatory response and by promoting antioxidation leading to the protection of pancreatic tissues. PMID:27525946

  5. Inflammatory Biomarkers as Differential Predictors of Antidepressant Response

    PubMed Central

    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

  6. Inflammatory biomarkers as differential predictors of antidepressant response.

    PubMed

    Hashimoto, Kenji

    2015-04-08

    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.

  7. Antidepressant treatment outcome depends on the quality of the living environment: a pre-clinical investigation in mice.

    PubMed

    Branchi, Igor; Santarelli, Sara; Capoccia, Sara; Poggini, Silvia; D'Andrea, Ivana; Cirulli, Francesca; Alleva, Enrico

    2013-01-01

    Antidepressants represent the standard treatment for major depression. However, their efficacy is variable and incomplete. A growing number of studies suggest that the environment plays a major role in determining the efficacy of these drugs, specifically of selective serotonin reuptake inhibitors (SSRI). A recent hypothesis posits that the increase in serotonin levels induced by SSRI may not affect mood per se, but enhances neural plasticity and, consequently, renders the individual more susceptible to the influence of the environment. Thus, SSRI administration in a favorable environment would lead to a reduction of symptoms, while in a stressful environment might lead to a worse prognosis. To test this hypothesis, we treated C57BL/6 adult male mice with chronic fluoxetine while exposing them to either (i) an enriched environment, after exposure to a chronic stress period aimed at inducing a depression-like phenotype, or (ii) a stressful environment. Anhedonia, brain BDNF and circulating corticosterone levels, considered endophenotypes of depression, were investigated. Mice treated with fluoxetine in an enriched condition improved their depression-like phenotype compared to controls, displaying higher saccharin preference, higher brain BDNF levels and reduced corticosterone levels. By contrast, when chronic fluoxetine administration occurred in a stressful condition, mice showed a more distinct worsening of the depression-like profile, displaying a faster decrease of saccharin preference, lower brain BDNF levels and increased corticosterone levels. Our findings suggest that the effect of SSRI on depression-like phenotypes in mice is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

  8. Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response

    PubMed Central

    Yuen, Genevieve S.; Gunning, Faith M.; Woods, Eric; Klimstra, Sibel A.; Hoptman, Matthew J.; Alexopoulos, George S.

    2014-01-01

    Background Apathy is a prominent feature of geriatric depression that predicts poor clinical outcomes and hinders depression treatment. Yet little is known about the neurobiology and treatment of apathy in late-life depression. This study examined apathy prevalence in a clinical sample of depressed elderly, response of apathy to selective serotonin reuptake inhibitor (SSRI) treatment, and neuroanatomical correlates that distinguished responders from nonresponders and healthy controls. Methods Participants included 45 non-demented, elderly with major depression and 43 elderly comparison individuals. After a 2-week single-blind placebo period, depressed participants received escitalopram 10mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Rating Scale (HDRS) were administered at baseline and 12 weeks. MRI scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate grey matter and associated white matter tracts. Results 35.5% of depressed patients suffered from apathy. This declined to 15.6% (p<0.1) following treatment, but 43% of initial sufferers continued to report significant apathy. Improvement of apathy with SSRI was independent of change in depression but correlated with larger left posterior subgenual cingulate volumes and greater fractional anisotropy of left uncinate fasciculi. Limitations modest sample size, no placebo control, post-hoc secondary analysis, use of 1.5T MRI scanner Conclusions While prevalent in geriatric depression, apathy is separable from depression with regards to medication response. Structural abnormalities of the posterior subgenual cingulate and uncinate fasciculus may perpetuate apathetic states by interfering with prefrontal cortical recruitment of limbic activity essential to motivated behavior. PMID:25012429

  9. 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

  10. ANXIETY AND DEPRESSIVE NEUROSIS - THEIR RESPONSE TO ANXIOLYTIC AND ANTIDEPRESSANT TREATMENT

    PubMed Central

    Singh, Gurmeet; Sharma, R.K.

    1987-01-01

    SUMMARY A total of 90 patients including 30 patients of generalized anxiety disorder and 30 of dysthymic disorder according to DSM III criteria plus 30 patients of mixed anxiety-depressive disorder were given a detailed psychiatric evaluation and four rating scales were made for measuring the level of anxiety and depression at intake and to record their improvement with treatment. Half the subjects in each group were randomly selected for treatment with imipramine and the other half with diazepam. Imipramine and diazepam were found to be equally effective (62.8% vs 62.2%) in reducing anxiety in all subjects. Imipramine was significantly better than diazepam in reducing the level of depression in the depressed group but as effective as diazepam in the other two groups. Imipramine was significantly better for the symptoms of ‘depressed mood’ and ‘retardation’, while diazepam was better in the symptom of ‘fears’. None of the other symptoms was discriminatory. PMID:21927208

  11. Antidepressants increase glial cell line-derived neurotrophic factor production through monoamine-independent activation of protein tyrosine kinase and extracellular signal-regulated kinase in glial cells.

    PubMed

    Hisaoka, Kazue; Takebayashi, Minoru; Tsuchioka, Mami; Maeda, Natsuko; Nakata, Yoshihiro; Yamawaki, Shigeto

    2007-04-01

    Recent studies show that neuronal and glial plasticity are important for therapeutic action of antidepressants. We previously reported that antidepressants increase glial cell line-derived neurotrophic factor (GDNF) production in rat C6 glioma cells (C6 cells). Here, we found that amitriptyline, a tricyclic antidepressant, increased both GDNF mRNA expression and release, which were selectively and completely inhibited by mitogen-activated protein kinase kinase inhibitors. Indeed, treatment of amitriptyline rapidly increased extracellular signal-regulated kinase (ERK) activity, as well as p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase activities. Furthermore, different classes of antidepressants also rapidly increased ERK activity. The extent of acute ERK activation and GDNF release were significantly correlated to each other in individual antidepressants, suggesting an important role of acute ERK activation in GDNF production. Furthermore, antidepressants increased the acute ERK activation and GDNF mRNA expression in normal human astrocytes as well as C6 cells. Although 5-hydroxytryptamine (serotonin) (5-HT), but not noradrenaline or dopamine, increased ERK activation and GDNF release via 5-HT2A receptors, ketanserin, a 5-HT2A receptor antagonist, did not have any effect on the amitriptyline-induced ERK activation. Thus, GDNF production by amitriptyline was independent of monoamine. Both of the amitriptyline-induced ERK activation and GDNF mRNA expression were blocked by genistein, a general protein tyrosine kinase (PTK) inhibitor. Actually, we found that amitriptyline acutely increased phosphorylation levels of several phosphotyrosine-containing proteins. Taken together, these findings indicate that ERK activation through PTK regulates antidepressant-induced GDNF production and that the GDNF production in glial cells may be a novel action of the antidepressant, which is independent of monoamine. PMID:17210798

  12. Circadian Rhythm Hypotheses of Mixed Features, Antidepressant Treatment Resistance, and Manic Switching in Bipolar Disorder

    PubMed Central

    Son, Gi-Hoon; Geum, Dongho

    2013-01-01

    Numerous hypotheses have been put forth over the years to explain the development of bipolar disorder. Of these, circadian rhythm hypotheses have gained much importance of late. While the hypothalamus-pituitary-adrenal (HPA) axis hyperactivation hypothesis and the monoamine hypothesis somewhat explain the pathogenic mechanism of depression, they do not provide an explanation for the development of mania/hypomania. Interestingly, all patients with bipolar disorder display significant disruption of circadian rhythms and sleep/wake cycles throughout their mood cycles. Indeed, mice carrying the Clock gene mutation exhibit an overall behavioral profile that is similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, and lower anxiety. It was recently reported that monoamine signaling is in fact regulated by the circadian system. Thus, circadian rhythm instability, imposed on the dysregulation of HPA axis and monoamine system, may in turn increase individual susceptibility for switching from depression to mania/hypomania. In addition to addressing the pathophysiologic mechanism underlying the manic switch, circadian rhythm hypotheses can explain other bipolar disorder-related phenomena such as treatment resistant depression and mixed features. PMID:24302944

  13. 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

  14. The ability of early changes in motivation to predict later antidepressant treatment response

    PubMed Central

    Gorwood, Philip; Vaiva, Guillaume; Corruble, Emmanuelle; Llorca, Pierre-Michel; Baylé, Franck J; Courtet, Philippe

    2015-01-01

    Introduction Baseline values and early changes of emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception have not been studied to any extent in unipolar depression, although they could help to characterize different dimensions of illness that are harder to capture by clinicians, give new insights on how patients improve, and offer new early clinical markers for later treatment response. Methods About 1,565 adult outpatients with major depressive disorder receiving agomelatine completed the clinician-rated 16-item quick inventory of depressive symptoms, Clinical Global Impression, and Multidimensional Assessment of Thymic States (MAThyS) rating scales at inclusion, Week 2 and Week 6. The MAThyS includes a 20-item self-rated visual analog scale (from inhibition [0] to activation [10], with [5] representing the usual state) leading to five a priori dimensions (emotional reactivity, cognitive speed, psychomotor function, motivation, and sensory perception). Results All MAThyS dimension scores increased from inclusion to Week 2 and from inclusion to Week 6 (P<0.001). Improvement was around 2 points (out of 10) for motivation, 1.5 points for psychomotor function, and 0.5 points for other dimensions. Motivation showed a trend to being more severely impaired at inclusion in future nonresponders (t=1.25, df=1,563, P=0.10). Its improvement at Week 2 was the most discriminating MAThyS dimension between future responders and nonresponders, and represents the best predictor of future response, with the highest area under the receptor operating characteristic curve (area under curve =0.616, 95% confidence interval [0.588–0.643], P<0.001). Finally, improvements in motivation correlated the most strongly with clinician-rated 16-item quick inventory of depressive symptoms improvement (r=−0.491, df=1,563, P<0.001). Conclusion Motivation had the most capacity for early improvement, the best predictive value for response, and the largest

  15. ANTIDEPRESSANT ACTIONS OF HDAC INHIBITORS

    PubMed Central

    Covington, Herbert E.; Maze, Ian; LaPlant, Quincey C.; Vialou, Vincent F.; Yoshinori, Ohnishi N.; Berton, Olivier; Fass, Dan M.; Renthal, William; Rush, Augustus J.; Wu, Emma Y.; Ghose, Subroto; Krishnan, Vaishnav; Russo, Scott J.; Tamminga, Carol; Haggarty, Stephen J.; Nestler, Eric J.

    2009-01-01

    Persistent symptoms of depression suggest the involvement of stable molecular adaptations in brain, which may be reflected at the level of chromatin remodeling. We find that chronic social defeat stress in mice causes a transient decrease, followed by a persistent increase, in levels of acetylated histone H3 in the nucleus accumbens, an important limbic brain region. This persistent increase in H3 acetylation is associated with decreased levels of histone deacetylase 2 (HDAC2) in the nucleus accumbens. Similar effects were observed in the nucleus accumbens of depressed humans studied postmortem. These changes in H3 acetylation and HDAC2 expression mediate long-lasting positive neuronal adaptations, since infusion of HDAC inhibitors into the nucleus accumbens, which increases histone acetylation, exerts robust antidepressant-like effects in the social defeat paradigm and other behavioral assays. HDAC inhibitor (MS-275) infusion also reverses the effects of chronic defeat stress on global patterns of gene expression in the nucleus accumbens, as determined by microarray analysis, with striking similarities to the effects of the standard antidepressant, fluoxetine. Stress-regulated genes whose expression is normalized selectively by MS-275 may provide promising targets for the future development of novel antidepressant treatments. Together, these findings provide new insight into the underlying molecular mechanisms of depression and antidepressant action, and support the antidepressant potential of HDAC inhibitors and perhaps other agents that act at the level of chromatin structure. PMID:19759294

  16. Sleep and cognition at baseline and the effects of REM sleep diminution after 1 week of antidepressive treatment in patients with depression.

    PubMed

    Göder, Robert; Seeck-Hirschner, Mareen; Stingele, Karoline; Huchzermeier, Christian; Kropp, Cornelia; Palaschewski, Milena; Aldenhoff, Josef; Koch, Jakob

    2011-12-01

    It has been hypothesized that non-rapid eye movement (NREM) sleep facilitates declarative memory consolidation, and rapid eye movement (REM) sleep is particularly important in promoting procedural learning. The aim of this study was to examine the effects of pharmacological REM sleep suppression on performance in different neuropsychological tasks. For our baseline, we chose 41 moderately depressed patients (age range 19-44 years), who were not taking antidepressants. In the morning after polysomnography, we tested memory recall and cognitive flexibility by assessment of verbal and figural fluency, a shift of attention task and the Trail Making Test B. After recording baseline values, patients were assigned randomly to one of three treatment groups: medication with citalopram; medication with reboxetine; or exclusive treatment with psychotherapy. Retesting took place 1 week after onset of treatment. The main results were: (1) an association of slow-wave sleep with verbal memory performance at baseline; (2) a suppression of REM sleep in patients taking citalopram and reboxetine; (3) no differences regarding neuropsychological performance within the treatment groups; and (4) no association of REM sleep diminution with decreases in memory performance or cognitive flexibility in patients treated with citalopram or reboxetine. In line with other studies, our results suggest that there are no negative effects of a decrease in REM sleep on memory performance in patients taking antidepressants.

  17. A pubertal immune challenge alters the antidepressant-like effects of chronic estradiol treatment in inbred and outbred adult female mice

    PubMed Central

    Ismail, Nafissa; Kumlin, Ashley M.; Blaustein, Jeffrey D.

    2012-01-01

    Puberty is a period characterized by brain reorganization that contributes to the development of neural and behavioral responses to gonadal steroids. A single injection of the bacterial endotoxin, lipopolysaccharide (LPS), during the pubertal period decreases sexual receptivity in response to ovarian hormones in adulthood. Because chronic estradiol treatment alleviates depression-like symptoms in ovariectomized adult mice, we investigated the effect of pubertal LPS treatment on estradiol’s antidepressant effects. We hypothesized that pubertal LPS treatment would decrease the antidepressant-like effect of estradiol in adult ovariectomized female mice, as it decreases other behavioral responses to ovarian hormones. As expected, chronic estradiol treatment decreased depression-like behavior, as measured by the duration of immobility, in saline-treated mice from two different strains, as well as in mice treated with LPS in adulthood. In contrast, in mice treated pubertally with LPS, estradiol strikingly increased the duration of immobility. No difference in body weight and in locomotion was found among the groups, suggesting that the differences in depression-like behavior were not due to differences in body weight or locomotor activity between LPS-treated and control mice. These results suggest that exposure to an immune challenge during the pubertal period alters the responsiveness of depression-like behavior to estradiol. PMID:23036617

  18. Antidepressants and psychotherapy: a clinical research review

    PubMed Central

    Frank, Ellen; Novick, Danielle; Kupfer, David J.

    2005-01-01

    This review focuses on information concerning antidepressants and psychotherapy in the treatement of both acute and chronic forms of unipolar depression in the English language literature. In it, we address the use of combination therapy, both from the outset of treatment and in a variety of sequences, ie, we examine the potential advantages of adding a targeted psychotherapy to an incompletely effective pharmacotherapy and the potential advantages of adding pharmacotherapy to an incompletely effective psychotherapy The number of research reports available to address these questions is small relative to their importance for clinical practice. There is a clear need for more information about the relative efficacy of pharmacotherapy-psychotherapy combinations or sequences versus either pharmacotherapy or psychotherapy provided as monotherapies. PMID:16156384

  19. New Hippocampal Neurons Mature Rapidly in Response to Ketamine But Are Not Required for Its Acute Antidepressant Effects on Neophagia in Rats123

    PubMed Central

    Soumier, Amelie; Carter, Rayna M.; Schoenfeld, Timothy J.

    2016-01-01

    Abstract Virtually all antidepressant agents increase the birth of granule neurons in the adult dentate gyrus in rodents, providing a key basis for the neurogenesis hypothesis of antidepressant action. The novel antidepressant ketamine, however, shows antidepressant activity in humans within hours, far too rapid for a mechanism involving neuronal birth. Ketamine could potentially act more rapidly by enhancing maturation of new neurons born weeks earlier. To test this possibility, we assessed the effects of S-ketamine (S-(+)-ketamine hydrochloride) injection on maturation, as well as birth and survival, of new dentate gyrus granule neurons in rats, using the immediate-early gene zif268, proliferating cell nuclear antigen, and BrdU, respectively. We show that S-ketamine has rapid effects on new neurons, increasing the proportion of functionally mature young granule neurons within 2 h. A single injection of S-ketamine also increased cell proliferation and functional maturation, and decreased depressive-like behavior, for at least 4 weeks in rats treated with long-term corticosterone administration (a depression model) and controls. However, the behavioral effects of S-ketamine on neophagia were unaffected by elimination of adult neurogenesis. Together, these results indicate that ketamine has surprisingly rapid and long-lasting effects on the recruitment of young neurons into hippocampal networks, but that ketamine has antidepressant-like effects that are independent of adult neurogenesis. PMID:27066531

  20. IC Treatment: Antidepressants

    MedlinePlus

    ... Children & IC La Cistitis Intersticial IC in Other Languages Associated Conditions Allergies and Sensitivities Celiac Disease Chronic ... Children & IC La Cistitis Intersticial IC in Other Languages Associated Conditions Allergies and Sensitivities Celiac Disease Chronic ...

  1. 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

  2. Tricyclic antidepressants for children with cancer.

    PubMed

    Pfefferbaum-Levine, B; Kumor, K; Cangir, A; Choroszy, M; Roseberry, E A

    1983-08-01

    Eight depressed children with cancer had a rapid clinical response to low doses of imipramine or amitriptyline. Because of the many variables affecting cancer patients, the mechanism by which tricyclic antidepressant treatment produced this response is unclear.

  3. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

    PubMed Central

    Fornaro, Michele; McCarthy, Michael J; De Berardis, Domenico; De Pasquale, Concetta; Tabaton, Massimo; Martino, Matteo; Colicchio, Salvatore; Cattaneo, Carlo Ignazio; D’Angelo, Emanuela; Fornaro, Pantaleo

    2013-01-01

    Purpose The circadian rhythm hypothesis of bipolar disorder (BD) suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute) or II cases of bipolar depression. Patients and methods Twenty-eight depressed BD-II patients received open label agomelatine (25 mg/bedtime) for 6 consecutive weeks as an adjunct to treatment with lithium or valproate, followed by an optional treatment extension of 30 weeks. Measures included the Hamilton depression scale, Pittsburgh Sleep Quality Index, the Clinical Global Impression Scale–Bipolar Version, Young Mania Rating Scale, and body mass index. Results Intent to treat analysis results demonstrated that 18 of the 28 subjects (64%) showed medication response after 6 weeks (primary study endpoint), while 24 of the 28 subjects (86%) responded by 36 weeks. When examining primary mood stabilizer treatment, 12 of the 17 (70.6%) valproate and six of the 11 (54.5%) lithium patients responded by the first endpoint. At 36 weeks, 14 valproate treated (82.4%) and 10 lithium treated (90.9%) subjects responded. At 36 weeks, there was a slight yet statistically significant (P = 0.001) reduction in body mass index and Pittsburgh Sleep Quality Index scores compared to respective baseline values, regardless of mood stabilizer/outcome. Treatment related drop-out cases included four patients (14.28%) at week 6 two valproate-treated subjects with pseudo-vertigo and drug-induced hypomania, respectively, and two lithium-treated subjects with insomnia and mania, respectively. Week 36 drop outs were two hypomanic cases, one per group. Conclusion Agomelatine 25 mg/day was an effective and well-tolerated adjunct to valproate/lithium for acute depression in BD-II, suggesting the need for confirmation by future double blind, controlled clinical trials. PMID:23430979

  4. Critical evaluation of mixed treatment comparison meta-analyses using examples assessing antidepressants and opioid detoxification treatments.

    PubMed

    Schacht, Alexander; Dyachkova, Yulia; Walton, Richard James

    2013-06-01

    Comparing multiple treatment options using meta-analytical methods requires complex statistical methods called mixed treatment comparisons (MTCs). Such methods offer the possibility to summarize data from many clinical trials comparing the different available options. However, those methods are based on a number of assumptions and inherent difficulties that are discussed and illustrated with examples from the psychiatric literature to help readers to understand the strengths and weaknesses of these methods. This review will help enable readers to critically appraise the methodology and results of publications that use MTCs.

  5. [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

  6. In the rat forced swimming test, NA-system mediated interactions may prevent the 5-HT properties of some subacute antidepressant treatments being expressed.

    PubMed

    Rénéric, Jean-Philippe; Bouvard, Manuel; Stinus, Luis

    2002-04-01

    In the rat forced swimming test (FST), reuptake inhibitors selective of either serotonin (5-HT) or noradrenaline (NA) decrease immobility duration, and increase, respectively, swimming and climbing behaviour. In this study, an almost total 6-OHDA-induced NA-depletion prevented the behavioural effects of desipramine, but not fluoxetine. Interestingly, the serotonin/noradrenaline-reuptake-inhibitor milnacipran, as well as a (desipramine+fluoxetine) combination, could produce both swimming and climbing behaviour in NA-lesioned rats, but not in non-lesioned. The new antidepressant mirtazapine, which enhances both 5-HT and NA transmissions, supposedly through the antagonizing of alpha(2)-adrenoreceptors, dose-dependently reduced immobility and increased climbing behaviour. Interestingly, a (mirtazapine+fluoxetine) combination treatment resulted in additive anti-immobility effects and in the summation of fluoxetine-induced swimming with mirtazapine-induced climbing. Taken together, these data suggest that the NA system mediates presynaptic inhibiting interactions on the 5-HT system, that may involve alpha(2)-receptors, and that may limit the efficacy of mixed serotonin/noradrenaline reuptake inhibition in subacute antidepressant treatments.

  7. 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.

  8. 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

  9. 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

  10. Antidepressant activity in mice elicited by 3-furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor.

    PubMed

    Targowska-Duda, Katarzyna M; Feuerbach, Dominik; Biala, Grazyna; Jozwiak, Krzysztof; Arias, Hugo R

    2014-05-21

    The objective of the current study is to determine whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of α7 nicotinic receptors (AChRs), produces antidepressant-like behavior in mice, and reactivates desensitized α7 AChRs expressed in CH3-α7 cells. Mice from both sexes were injected (i.p.) with PAM-2 (1.0mg/kg) on a daily basis for three weeks. Forced swim tests (FSTs) were performed on Day 1 and Day 7 to determine the acute and subchronic effects of PAM-2, respectively, and on Days 14 and 21 to determine its chronic activity. To examine the residual effects after drug treatment, a withdrawal period of two more weeks was continued with FSTs performed on Day 28 and 35. Our results indicate that: (1) PAM-2 does not induce acute antidepressant effects in male or female mice, (2) PAM-2 induces antidepressant effects in mice from both sexes after one (subchronic) and two (chronic) weeks, whereas at the third week (chronic), the antidepressant effect is decreased in male and increased in female mice. Since PAM-2 does not influence the locomotor activity of mice, the observed antidepressant activity is not driven by nonspecific motor-stimulant actions, (3) the residual antidepressant effect mediated by PAM-2 after one week of treatment cessation is observed only in female mice, and finally the Ca(2+) influx results indicate that (4) PAM-2 can reactivate desensitized α7 AChRs. Our results clearly indicate that PAM-2 elicits antidepressant activity, probably by enhancing the activity of the endogenous neurotransmitter acetylcholine on α7 AChRs, without inducing receptor desensitization, and that this activity is gender-dependent. This is the first time that an antidepressant activity is described for an α7 PAM, supporting further studies as potential therapeutic medications for depressive states. PMID:24708923

  11. 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

  12. Evaluation of the Effectiveness of a Psychoeducational Intervention in Treatment-Naïve Patients with Antidepressant Medication in Primary Care: A Randomized Controlled Trial

    PubMed Central

    Casañas, R.; Catalán, R.; Penadés, R.; Real, J.; Valero, S.; Muñoz, MA.; Lalucat-Jo, LL.; Casas, M.

    2015-01-01

    Background. There is evidence supporting the effectiveness of psychoeducation (PE) in patients with symptoms of depression in primary care (PC), but very few studies have assessed this intervention in antidepressant-naïve patients. The aim of this study is to assess the effectiveness of a PE program in these patients, since the use of antidepressant (AD) medication may interfere with the effects of the intervention. Methods. 106 participants were included, 50 from the PE program (12 weekly 1.5-hour sessions) and 56 from the control group (CG) that received the usual care. Patients were assessed at baseline and at 3, 6, and 9 months. The main outcome measures were the Beck Depression Inventory (BDI) and remission based on the BDI. The analysis was carried out on an intention-to-treat basis. Results. The PE program group showed remission of symptoms of 40% (P = 0.001) posttreatment and 42% (P = 0.012) at 6 months. The analysis only showed significant differences in the BDI score posttreatment (P = 0.008; effect size Cohen's d′ = 0.55). Conclusions. The PE intervention is an effective treatment in the depressive population not treated with AD medication. Before taking an AD, psychoeducational intervention should be considered. PMID:26380366

  13. Investigations of morning and laboratory dream recall and content in depressive patients during baseline conditions and under antidepressive treatment with trimipramine.

    PubMed

    Riemann, D; Löw, H; Schredl, M; Wiegand, M; Dippel, B; Berger, M

    1990-06-01

    REM sleep abnormalities like shortened REM (rapid eye movement) latency, prolongation of the first REM period and heightening of REM density often found in patients with a major depression have prompted an increasing number of studies investigating the neurobiology and neurophysiology of REM sleep in depressive patients, as well as in healthy humans and animals. On the other hand, since the early 1970s investigation of the psychological concomitant of REM sleep, i.e., dreaming, in depressive patients has been extremely sparse. The present study aimed at investigating morning and laboratory dream recall and content in patients with a major depressive disorder to shed more light on this neglected area. In short, morning as well as laboratory dream recall in depressive inpatients was drastically reduced. The low number of scorable dream reports collected did not reveal a heightened incidence of "masochistic" or "negative" content, indeed were rather mundane. In contrast, depressive outpatients (probably less depressed) had a higher rate of morning dream recall. Interestingly, antidepressive treatment with trimipramine (an antidepressant which does not suppress REM sleep) led to a positive influence on patients' mood that was paralleled by a change of dream mood in a positive direction.

  14. Evolving Role of Endovascular Treatment of Acute Ischemic Stroke

    PubMed Central

    del Zoppo, Gregory J.

    2014-01-01

    The perceived advantages of endovascular treatment for acute ischemic stroke in terms of recanalization, the multimodal and targeted approaches, and perhaps the more permissive rules on devices than on medications for their licensing favored the assumption that endovascular treatment is superior to intravenous thrombolysis for acute treatment of ischemic stroke, and its adoption in more advanced stroke centers. However, this assumption has been questioned by recent clinical trial experience showing that endovascular treatment is not superior to intravenous thrombolysis. The new evidence has changed the perception and the importance of conducting randomized trials in this area. This summary examines the background and outcomes of the latest experience with endovascular techniques in acute stroke treatment based on historical data. The new challenge is how to study the latest generation of devices called stent retrievers, which are faster in recanalizing and easier to use, in selected patients with acute ischemic stroke. In the meantime, the available evidence does not provide support for the use of endovascular treatment of acute ischemic stroke in clinical practice. PMID:24258466

  15. Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder

    PubMed Central

    2011-01-01

    Background In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD. Methods/Design The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence. Discussion This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently disappointing remission rates

  16. Surfactant treatment for acute respiratory distress syndrome

    PubMed Central

    Lopez-Herce, J.; de Lucas, N.; Carrillo, A.; Bustinza, A.; Moral, R.

    1999-01-01

    OBJECTIVE—To determine prospectively the efficacy of surfactant in acute respiratory distress syndrome.
STUDY DESIGN—Twenty patients, 1 month to 16 years of age, diagnosed with an acute pulmonary disease with severe hypoxaemia (PaO2/FiO2 < 100) (13 with systemic or pulmonary disease and seven with cardiac disease) were treated with one to six doses of 50-200 mg/kg of porcine surfactant administered directly into the trachea. The surfactant was considered to be effective when the PaO2/FiO2 improved by > 20%.
RESULTS—After initial surfactant administration the PaO2/FiO2 increased significantly in patients with systemic or pulmonary disease from 68 to 111, and the oxygenation index (OI) diminished significantly from 36.9 to 27.1. The PaO2/FiO2 and OI did not improve in children with cardiac disease. The improvement of the patients who survived was greater than that of those who died.
CONCLUSIONS—Surfactant moderately improves oxygenation in some children with severe acute respiratory distress syndrome secondary to pulmonary or systemic disease.

 PMID:10325705

  17. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed.

  18. 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

  19. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    ERIC Educational Resources Information Center

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  20. Aneurysm Formation After Endovascular Treatment of Acute Type A Dissection.

    PubMed

    Yang, Lai; Wang, Jiaping

    2016-08-01

    Recently, reports have described successful endovascular stent graft (ESG) treatment of patients with acute type A aortic dissection. We report 1 ESG treatment for this condition and the complication of a new aneurysm formation during a 6-month follow-up. PMID:27630269

  1. Acute intermittent porphyria: Diagnostic dilemma and treatment options

    PubMed Central

    Kaur, Mohan Deep; Hazarika, Nita; Saraswat, Namita; Sood, Rajesh

    2015-01-01

    Acute intermittent porphyria (AIP) presents with diverse group of symptoms making its early diagnosis difficult. Delaying diagnosis and treatment of AIP can be fatal or can cause long term or permanent neurological damage. We present here a case report of AIP where the diagnosis was missed. The diversity of symptoms and details concerning the treatment options for AIP are discussed. PMID:26330726

  2. Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action

    PubMed Central

    Cao, Jun-Li; Covington, Herbert E; Friedman, Allyson K; Wilkinson, Matthew B; Walsh, Jessica J; Cooper, Donald C; Nestler, Eric J; Han, Ming-Hu

    2010-01-01

    We previously reported that the activity of mesolimbic dopamine neurons of the ventral tegmental area (VTA) is a key determinant of behavioral susceptibility vs. resilience to chronic social defeat stress. However, this was based solely on ex vivo measurements, and the in vivo firing properties of VTA dopamine neurons in susceptible and resilient mice, as well as the effects of antidepressant treatments, remain completely unknown. Here, we show that chronic (10-day) social defeat stress significantly increased the in vivo spontaneous firing rates and bursting events in susceptible mice but not in the resilient subgroup. Both the firing rates and bursting events were significantly negatively correlated with social avoidance behavior, a key behavioral abnormality induced by chronic social defeat stress. Moreover, the increased firing rates, bursting events, and avoidance behavior in susceptible mice were completely reversed by chronic (2-week), but not acute (single dose), treatments with the antidepressant medication, fluoxetine (20 mg/Kg). Chronic social defeat stress increased hyperpolarization-activated cation current (Ih) in VTA dopamine neurons, an effect which was also normalized by chronic treatment with fluoxetine. As well, local infusion of Ih inhibitors ZD7288 (0.1 μg) or DK- AH 269 (0.6 μg) into the VTA exerted antidepressant-like behavioral effects. Together, these data suggest that the firing patterns of mesolimbic dopamine neurons in vivo mediate an individual’s responses to chronic stress and antidepressant action. PMID:21147984

  3. Acute appendicitis: What is the gold standard of treatment?

    PubMed Central

    Ruffolo, Cesare; Fiorot, Alain; Pagura, Giulia; Antoniutti, Michele; Massani, Marco; Caratozzolo, Ezio; Bonariol, Luca; Calia di Pinto, Francesco; Bassi, Nicolò

    2013-01-01

    McBurney’s procedure represented the gold-standard for acute appendicitis until 1981, but nowadays the number of laparoscopic appendectomies has progressively increased since it has been demonstrated to be a safe procedure, with excellent cosmetic results and it also allows a shorter hospitalization, a quicker and less painful postoperative recovery. The aim of this editorial was to perform a review of the literature in order to address controversial issues in the treatment of acute appendicitis. PMID:24379603

  4. Pediatric Acute Bacterial Sinusitis: Diagnostic and Treatment Dilemmas.

    PubMed

    Fang, Andrea; England, Jasmin; Gausche-Hill, Marianne

    2015-11-01

    Acute bacterial sinusitis (ABS) is a common complication of a simple upper respiratory infection. Acute bacterial sinusitis and an upper respiratory infection, however, have different management plans. This article will help clinicians establish when a diagnosis of ABS can be made based on the latest guidelines from the American Academy of Pediatrics. Also covered will be the pathophysiology of ABS, the role of diagnostic imaging, the recognition of complications of ABS, and treatment options.

  5. Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression.

    PubMed

    Bech, P

    2001-12-01

    When attempting to demonstrate a purely antidepressive effect of new antidepressants the HAMD depression factor has been found adequate in placebo-controlled trials. When attempting to demonstrate an early onset of action of amitriptyline the HAMD item of depressed mood has previously been found sufficient, using effect size as outcome statistic. Therefore, the HAMD depression factor as well as the HAMD item of depressed mood have been used separately in this meta-analysis to evaluate the pure antidepressive effect and early onset of action of mirtazapine when compared to placebo or amitriptyline. The results showed that in all placebo-controlled trials mirtazapine obtained an effect size of 0.42 on the HAMD depression factor subscale and 0.49 on the full HAMD. In the trials in which mirtazapine was compared to amitriptyline the effect sizes for the HAMD depression factor subscale were 0.40 and 0.57, respectively. This difference was not statistically significant. An early onset of action was found for the HAMD item of depressed mood as well as the total HAMD both for mirtazapine and amitriptyline when compared to placebo. As early as after 1 wk of therapy both drugs were significantly better than placebo. In conclusion, a purely antidepressive effect of mirtazapine has been demonstrated concerning both improvement after the acute therapy of major depression and early onset of action.

  6. 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

  7. Chronic mild stress and antidepressant treatment alter 5-HT1A receptor expression by modifying DNA methylation of a conserved Sp4 site.

    PubMed

    Le François, Brice; Soo, Jeremy; Millar, Anne M; Daigle, Mireille; Le Guisquet, Anne-Marie; Leman, Samuel; Minier, Frédéric; Belzung, Catherine; Albert, Paul R

    2015-10-01

    The serotonin 1A receptor (5-HT1A), a critical regulator of the brain serotonergic tone, is implicated in major depressive disorder (MDD) where it is often found to be dys-regulated. However, the extent to which stress and antidepressant treatment impact 5-HT1A expression in adults remains unclear. To address this issue, we subjected adult male BALB/c mice to unpredictable chronic mild stress (UCMS) to induce a depression-like phenotype that was reversed by chronic treatment with the antidepressant imipramine. In prefrontal cortex (PFC) and midbrain tissue, UCMS increased 5-HT1A RNA and protein levels, changes that are expected to decrease the brain serotonergic activity. The stress-induced increase in 5-HT1A expression was paralleled by a specific increase in DNA methylation of the conserved -681 CpG promoter site, located within a Sp1-like element. We show that the -681 CpG site is recognized and repressed by Sp4, the predominant neuronal Sp1-like factor and that Sp4-induced repression is attenuated by DNA methylation, despite a stress-induced increase in PFC Sp4 levels. These results indicate that adult life stress induces DNA methylation of a conserved promoter site, antagonizing Sp4 repression to increase 5-HT1A expression. Chronic imipramine treatment fully reversed the UCMS-induced increase in methylation of the -681 CpG site in the PFC but not midbrain of stressed animals and also increased 5-HT1A expression in the PFC of control animals. Incomplete reversal by imipramine of stress-induced changes in 5-HT1A methylation and expression indicates a persistence of stress vulnerability, and that sustained reversal of behavioral impairments may require additional pathways.

  8. 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

  9. Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis.

    PubMed

    Hadley, James A; Tillotson, Glenn S; Tosiello, Robert; Echols, Roger M

    2006-12-01

    Faropenem medoxomil is the first oral penem in a new class of beta-lactam antibiotics. Faropenem medoxomil has excellent in vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and other key pathogens implicated in acute bacterial rhinosinusitis. Clinical studies have demonstrated that, in the treatment of acute bacterial rhinosinusitis in adults, 7 days of treatment with faropenem medoxomil is as clinically and bacteriologically effective as 10 days of treatment with cefuroxime axetil. One study showed faropenem medoxomil to be superior to cefuroxime axetil. Overall, the safety profile of faropenem medoxomil is similar to that of most comparators. Specifically, the minimal impact of faropenem medoxomil on the gastrointestinal flora leads to less diarrhea and other adverse events than coamoxicillin-clavulanate. Faropenem medoxomil has almost no drug-drug interactions and little requirement for dosage adjustments in the typical acute rhinosinusitis population. PMID:17181408

  10. Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim.

    PubMed

    Molina-Hernández, Miguel; Tellez-Alcántara, Norma Patricia; García, Julían Pérez; Lopez, Jorge Ivan Olivera; Jaramillo, M Teresa

    2004-12-01

    This article was aimed to investigate the interest of the combination allopregnanolone plus ketoconazole in depression with the time-sampling method in the forced swimming task. Dose-response curves for fluoxetine (0.5, 1.0 or 2.0 mg/kg, twice day, during 2 weeks; i.p.), desipramine (0.5, 1.0 or 2.14 mg/kg, twice a day, during 2 weeks; i.p.), ketoconazole (6.25, 12.5, 25.0 and 37.5 mg/kg, once a day, during 2 weeks; i.p.) and allopregnanolone (0.5, 1.5, 2.0 mg/kg; once a day, during 2 weeks; s.c.) were established. Fluoxetine (1.0 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) or ketoconazole (25.0 mg/kg, p < 0.05; 37.5 mg/kg, p < 0.05) produced antidepressant-like behavioral changes in swimming, highlighting a serotonergic mechanism while desipramine (1.0 mg/kg, p < 0.05; 2.14 mg/kg, p < 0.05) or allopregnanolone (1.5 mg/kg, p < 0.05; 2.0 mg/kg, p < 0.05) increased climbing behavior highlighting noradrenergic or dopaminergic effects. Subthreshold doses of fluoxetine (p < 0.05), desipramine (p < 0.05) or ketoconazole (p < 0.05) synergized with subthreshold doses of allopregnanolone and reduced immobility by increasing climbing. In conclusion, fluoxetine, desipramine, ketoconazole and allopregnanolone produced differential antidepressant-like actions in ovariectomized rats forced to swim. Ketoconazole, fluoxetine or desipramine synergized with allopregnanolone.

  11. Comparison of two main treatment modalities for acute ankle sprain

    PubMed Central

    Bilgic, Serkan; Durusu, Murat; Aliyev, Bahtiyar; Akpancar, Serkan; Ersen, Omer; Yasar, S.Mehmet; Ardic, Sukru

    2015-01-01

    Objective: Acute ankle sprains are one of the most common injuries in emergency departments. Immobilization is widely accepted as the basic treatment modality for acute ankle sprains; however, immobilization method remains controversial. In this study, we aimed to compare two treatment modalities: splint and elastic bandage for the management of acute ankle sprains. Methods: This prospective study was conducted in the emergency department. Fifty-one consecutive patients who were admitted to the emergency department owing to the complaint of ankle sprain and who were treated with an elastic bandage or a splint were included in the study. After bone injury was ruled out, treatment choice was left to the on-shift physicians’ discretion. The extent of edema was evaluated before and after the treatment by using a small, graduated container filled with warm water. Volume differences were calculated by immersing both lower extremities in a container filled to a constant level. Pain was evaluated using the visual analogue scale. Results: There were 25 patients in the elastic bandage group and 26 patients in the splint group. VAS scores of these groups before and after the treatment were similar. Although edema size before and after the treatment were similar between the groups, edema size reduction was significantly more in the elastic bandage group [p=0,025]. Conclusions: This study showed that treatment of acute ankle sprains with an elastic bandage was more effective than splint in reducing edema. Therefore, an elastic bandage could be preferred over a splint for the treatment of acute ankle sprains. PMID:26870123

  12. Endovascular treatment of acute ischemic stroke.

    PubMed

    Kidwell, Chelsea S; Jahan, Reza

    2015-05-01

    Endovascular therapy for acute stroke has evolved with the use of intra-arterial thrombolytics, intravenous/intra-arterial bridging strategies, and mechanical thrombectomy/aspiration devices. Despite widespread use in clinical practice, randomized trials of first-generation devices failed to demonstrate improved outcomes compared with standard care. New-generation stent retriever devices demonstrate higher rates of revascularization and clinical outcomes compared with first-generation devices. Additional randomized trials are underway and have the potential to confirm clinical efficacy of new-generation devices compared with standard care. The role of additional advanced imaging for patient selection remains unclear, and further trials are needed to demonstrate the role of these techniques for patient selection. PMID:25907913

  13. Diagnosis and treatment of acute extremity compartment syndrome.

    PubMed

    von Keudell, Arvind G; Weaver, Michael J; Appleton, Paul T; Appelton, Paul T; Bae, Donald S; Dyer, George S M; Heng, Marilyn; Jupiter, Jesse B; Vrahas, Mark S

    2015-09-26

    Acute compartment syndrome of the extremities is well known, but diagnosis can be challenging. Ineffective treatment can have devastating consequences, such as permanent dysaesthesia, ischaemic contractures, muscle dysfunction, loss of limb, and even loss of life. Despite many studies, there is no consensus about the way in which acute extremity compartment syndromes should be diagnosed. Many surgeons suggest continuous monitoring of intracompartmental pressure for all patients who have high-risk extremity injuries, whereas others suggest aggressive surgical intervention if acute compartment syndrome is even suspected. Although surgical fasciotomy might reduce intracompartmental pressure, this procedure also carries the risk of long-term complications. In this paper in The Lancet Series about emergency surgery we summarise the available data on acute extremity compartment syndrome of the upper and lower extremities in adults and children, discuss the underlying pathophysiology, and propose a clinical guideline based on the available data.

  14. Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change.

    PubMed

    Lopresti, Adrian L; Maes, Michael; Meddens, Marc J M; Maker, Garth L; Arnoldussen, Eddy; Drummond, Peter D

    2015-01-01

    A recent randomised, double-blind, placebo controlled study conducted by our research group, provided partial support for the efficacy of supplementation with a patented curcumin extract (500 mg, twice daily) for 8 weeks in reducing depressive symptoms in people with major depressive disorder. In the present paper, a secondary, exploratory analysis of salivary, urinary and blood biomarkers collected during this study was conducted to identify potential antidepressant mechanisms of action of curcumin. Pre and post-intervention samples were provided by 50 participants diagnosed with major depressive disorder, and the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) was used as the primary depression outcome measure. Compared to placebo, 8 weeks of curcumin supplementation was associated with elevations in urinary thromboxane B2 (p<0.05), and substance P (p<0.001); while placebo supplementation was associated with reductions in aldosterone (p<0.05) and cortisol (p<0.05). Higher baseline plasma endothelin-1 (rs=-0.587; p<0.01) and leptin (rs=-0.470; p<0.05) in curcumin-treated individuals was associated with greater reductions in IDS-SR30 score after 8 weeks of treatment. Our findings demonstrate that curcumin supplementation influences several biomarkers that may be associated with its antidepressant mechanisms of action. Plasma concentrations of leptin and endothelin-1 seem to have particular relevance to treatment outcome. Further investigations using larger samples sizes are required to elucidate these findings, as the multiple statistical comparisons completed in this study increased the risk of type I errors.

  15. Distribution of antidepressants and their metabolites in brook trout exposed to municipal wastewaters before and after ozone treatment--evidence of biological effects.

    PubMed

    Lajeunesse, André; Gagnon, Christian; Gagné, François; Louis, Séverine; Cejka, Patrick; Sauvé, Sébastien

    2011-04-01

    This study examined the tissues distribution of selected serotonin reuptake inhibitors (SSRIs) in brook trout exposed for 3 months to continuous flow-through primary-treated effluent before and after ozone treatment. A reliable analytical method was developed for the quantification of trace amounts of antidepressants in small tissue homogenate extracts. Levels of six antidepressants and four of their N-desmethyl metabolites were determined using liquid chromatography-tandem mass spectrometry. Significant amounts of the SSRIs were found in fish tissue-in decreasing order: liver>brain>muscle. Sertraline and its metabolite desmethylsertraline were the predominant substances observed in most tissues (0.04-10.3 ng g(-1)). However, less SSRIs (0.08-1.17 ng g(-1)) were bioaccumulated in the ozonated effluent. The early molecular effects of these SSRIs on the Na/K-dependent ATPase pump activity in brain synaptosomes where also investigated in vitro and in fish exposed to the municipal effluents. With respect to their potential biological effects, in vitro exposure to selected SSRIs induced a reduction of the brain Na/K-ATPase activity in synaptosomes in a dose-dependent manner. Results showed that Na/K-ATPase activity was readily inhibited by exposure to municipal effluent before and, to a lesser extent, after ozone treatment. Moreover, the Na/K-ATPase activity was significantly and negatively correlated with brain tissue concentrations of fluoxetine (r=-0.57; p<0.03), desmethylsertraline (r=-0.84; p<0.001), and sertraline (r=-0.82; p<0.001). The present study reveals that SSRIs are readily available in fish, biologically active and corroborates previous findings on the serotonergic properties of municipal effluents to aquatic organisms. PMID:21211816

  16. Screening of the antidepressant-like effect of the traditional Chinese medicinal formula Si-Ni-San and their possible mechanism of action in mice

    PubMed Central

    Yi, Li-Tao; Li, Jing; Liu, Bin-Bin; Li, Cheng-Fu

    2013-01-01

    Background: The traditional Chinese medicine formula Si-Ni-San has well therapeutic applications in improvement of mental diseases including depression. However, the neuropharmacological and neuroendocrine mechanisms of the formula on antidepressant-like action have not been reported. Objective: Herein, we explored the antidepressant-like effect and its mechanism of Si-Ni-San. Materials and Methods: Acute effect of Si-Ni-San on the immobility time was assessed in the mouse forced swim test (FST) and tail suspension test (TST). Moreover, we investigated the neurochemical, neuroendocrine, and neurotrophin systems involved in the antidepressant-like effect of this formula. Results: Si-Ni-San significantly decreased the immobility time after acute treatment in the mouse TST (1300 mg/kg) but not in the FST compared with the control group. In addition, pretreatment of mice with PCPA or AMPT prevented the anti-immobility effect of Si-Ni-San (1300 mg/kg) in the TST. Moreover, acute Si-Ni-San (1300 mg/kg) decreased serum corticosterone levels, elevated serotonin (5-HT), norepinephrine (NE), and dopamine (DA) levels without affecting brain-derived neurotrophic factor (BDNF) levels in the whole brain exposed to TST. Conclusion: The acute antidepressant-like action of Si-Ni-San is mediated by the monoaminergic and neuroendocrine systems although underlying mechanism still remains to be further elucidated, and this formula should be further investigated as an alternative therapeutic approach for the treatment of depression. PMID:23598923

  17. Antidepressant-like effects in various mice strains in the tail suspension test.

    PubMed

    Ripoll, Nadège; David, Denis Joseph Paul; Dailly, Eric; Hascoët, Martine; Bourin, Michel

    2003-08-14

    Several studies have reported rodent strain differences in the response to antidepressants in animal models of depression. The aim of the present study was to investigate the potential contribution of genetic factors to antidepressant response in an animal model of depression: the tail suspension test (TST). For this study four mice strains (Swiss and NMRI, two outbred strains and DBA/2 and C57BL/6J Rj, two inbred strains) were submitted to the TST after acute administration of five antidepressants: the tricyclic antidepressants (TCAs) imipramine and desipramine, the selective serotonin (5-HT) reuptake inhibitors (SSRIs) paroxetine and citalopram and the dopamine reuptake inhibitor bupropion. The C57BL/6J Rj strain had a longer baseline immobility time in comparison to the other strains. All antidepressants studied in this work decreased immobility time in the Swiss and C57BL/6J Rj strains. However, the Swiss strain displayed greater sensitivity to citalopram (from 2mg/kg) and C57BL/6J Rj to paroxetine (from 0.5mg/kg). This latter presented a greater size-effect with citalopram than with other strains and reached more than 60% from 8mg/kg. Moreover the size-effect of desipramine, paroxetine and bupropion in Swiss mice was greater than in the other strains in the TST. The NMRI and DBA/2 mice only responded to 5-HT reuptake inhibitors, both selective (paroxetine, citalopram) or non-selective (imipramine). The NMRI strain was more sensitive to imipramine and presented a size-effect (43% at 8mg/kg) superior to those of other strains. DBA/2 strain was more sensitive to citalopram than paroxetine and imipramine. Our results suggest that response to an antidepressant treatment is under control of genetic factors and that the strain of mouse is an important parameter to consider.

  18. Epidemiology and Treatment of Acute Promyelocytic Leukemia in Latin America

    PubMed Central

    Rego, E.M.; Jácomo, R.H.

    2011-01-01

    Distinct epidemiological characteristics have been described in Acute Promielocytic Leukemia (APL). Populations from Latin America have a higher incidence of APL and in some geographic areas a distinct distribution of the PML-RARA isoforms is present. Here, we review the main differences in APL epidemilogy in Latin America as well as treatment outcomes. PMID:22110899

  19. Endovascular Treatment of Acute Thrombosis of Cerebral Veins and Sinuses

    PubMed Central

    Yakovlev, Sergey Borisovich; Bocharov, Aleksei Vasilievich; Mikeladze, Ketevan; Gasparian, Sergey Surenovich; Serova, Natalia Konstantinovna; Shakhnovich, Alexander Romanovich

    2014-01-01

    Summary Acute thrombosis of cerebral veins and sinuses (ATCVS) is a multifactorial disease with grave consequences. Because of its rare occurrence there are no proven treatment guidelines. Sixteen patients with ATCVS were treated. The final diagnosis was confirmed by digital subtraction angiography. Sinus catheterization was performed via transfemoral venous access. Treatment included mechanical manipulation of thrombi and thrombolytic therapy. A regression of clinical symptoms with a concomitant decrease of intracranial hypertension was achieved in all patients. Long-term results were studied in eight patients: none presented clinical signs of intracranial hypertension. Endovascular transvenous recanalization is an effective treatment for acute thrombosis of cerebral veins and sinuses. Along with the local thrombolysis, significant potential in the treatment of this complex pathology lies in the transvenous endovascular techniques of mechanical thrombus extraction, especially in patients with intracranial hemorrhage for whom the use of thrombolytic agents is restricted. PMID:25196622

  20. The antidepressant-like activity of nicotine, but not of 3-furan-2-yl-N-p-tolyl-acrylamide, is regulated by the nicotinic receptor β4 subunit.

    PubMed

    Arias, Hugo R; Targowska-Duda, Katarzyna M; Feuerbach, Dominik; Jozwiak, Krzysztof

    2015-08-01

    The current study compares the antidepressant-like effect elicited by nicotine between wild-type (β4+/+) and knockout (β4-/-) mice, and subsequently, the effect of 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of α7 nicotinic receptors, on the previously determined activity of nicotine. Mice from each sex were injected daily with nicotine base (0.2 mg/kg; s.c.) or co-administered with PAM-2 (1.0 mg/kg; i.p.) for 3 weeks. Forced swim tests were performed to determine the acute (day 1), subchronic (day 7), and chronic (days 14 and 21) effects of the drugs, as well as their residual effects after treatment cessation (days 28 and 35). Our results indicate that nicotine mediates antidepressant-like activity after acute, subchronic, and chronic treatments in β4+/+, but not β4-/-, mice, and that these effects are not mediated by unspecific locomotor stimulation. Nicotine co-administered with PAM-2 produces antidepressant-like activity in both β4+/+ and β4-/- mice, except after the acute treatment of β4-/- mice, and decreases locomotor activity. This suggests that although the β4 subunit regulates the antidepressant-like activity of nicotine it does not affect the activity elicited by PAM-2 when is co-administered with nicotine. The residual antidepressant-like activity of PAM-2 + nicotine was observed only in female mice, suggesting gender-specific differences. Our findings clearly indicate that β4-containing nAChRs play an important role in the antidepressant-like activity elicited by nicotine but they are not essential for the modulatory activity of PAM-2. In fact, PAM-2 inhibits α4β4 and α3β4 AChRs at higher concentration ranges compared to that for the PAM activity previously found at the α7 AChR.

  1. Transcriptomics and the mechanisms of antidepressant efficacy.

    PubMed

    Hodgson, Karen; Tansey, Katherine E; Powell, Timothy R; Coppola, Giovanni; Uher, Rudolf; Zvezdana Dernovšek, Mojca; Mors, Ole; Hauser, Joanna; Souery, Daniel; Maier, Wolfgang; Henigsberg, Neven; Rietschel, Marcella; Placentino, Anna; Aitchison, Katherine J; Craig, Ian W; Farmer, Anne E; Breen, Gerome; McGuffin, Peter; Dobson, Richard

    2016-01-01

    The mechanisms by which antidepressants have their effects are not clear and the reasons for variability in treatment outcomes are also unknown. However, there is evidence from candidate gene research that indicates gene expression changes may be involved in antidepressant action. In this study, we examined antidepressant-induced alterations in gene expression on a transcriptome-wide scale, exploring associations with treatment response. Blood samples were taken from a subset of depressed patients from the GENDEP study (n=136) before and after eight weeks of treatment with either escitalopram or nortriptyline. Transcriptomic data were obtained from these samples using Illumina HumanHT-12 v4 Expression BeadChip microarrays. When analysing individual genes, we observed that changes in the expression of two genes (MMP28 and KXD1) were associated with better response to nortriptyline. Considering connectivity between genes, we identified modules of genes that were highly coexpressed. In the whole sample, changes in one of the ten identified coexpression modules showed significant correlation with treatment response (cor=0.27, p=0.0029). Using transcriptomic approaches, we have identified gene expression correlates of the therapeutic effects of antidepressants, highlighting possible molecular pathways involved in efficacious antidepressant treatment.

  2. Outcome measures of antidepressive therapy.

    PubMed

    Rosenberg, R

    2000-01-01

    A variety of outcome measures assessing antidepressive therapy are available. However, in randomized clinical trials, the Hamilton Rating Scale for Depression (HAM-D) is often the primary outcome measure. Results from factor analysis and Rasch item analysis indicate that the HAM-D is heterogeneous and that the sum of items scores may not be an adequate measure of the severity of depression. A Melancholia Scale of 11 items has been suggested as a more valid measure of the core symptoms of affective syndrome. Other global outcome measures, focusing on health-related quality of life issues and on social functioning as well as macro-economic analyses are also used in depression. Applying stringent and well-documented outcome measures in randomized clinical trials of antidepressants may give the clinician a better indication of the most appropriate drug for treatment of the individual patient.

  3. Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents

    PubMed Central

    O’Brien, Kimberly H. McManama; Singer, Jonathan B.; LeCloux, Mary; Duarté-Vélez, Yovanska; Spirito, Anthony

    2015-01-01

    Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID:26279646

  4. 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

  5. Acute treatment of anaphylaxis in children

    PubMed Central

    Goldman, Ran D.

    2013-01-01

    Abstract Question A 3-year-old was rushed to my office after eating a friend’s chocolate bar that contained nuts. He immediately developed urticaria on his face and swelling of his lips, and he had a persistent cough. What is the best treatment for a child with anaphylaxis? Should this family receive a prescription for an epinephrine autoinjector device? Answer Intramuscular epinephrine injection is a safe and effective treatment of anaphylaxis in children. Children with systemic allergic reactions should carry epinephrine autoinjectors at all times, and should certainly have one with them at school. In order for epinephrine autoinjectors to be effective, children and their families need to be educated on how to properly use the devices, as well as keep in mind the product’s expiration date. PMID:23851537

  6. Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

    PubMed Central

    Renoir, Thibault

    2013-01-01

    Besides demonstrated efficacy, selective serotonin reuptake inhibitors (SSRIs) hold other advantages over earlier antidepressants such as greater tolerability and a wider range of clinical applications. However, there is a growing body of clinical evidence which suggests that SSRIs could, in some cases, be associated with a withdrawal reaction upon cessation of regular use. In addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances. Psychological symptoms have also been documented, usually developing within 1–7 days following SSRI discontinuation. The characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs. However, many aspects of the neurobiology of the SSRI discontinuation syndrome (or SSRI withdrawal syndrome) remain unresolved. Following a comprehensive overview of the clinical evidence, we will discuss the underlying pathophysiology of the SSRI discontinuation syndrome and comment on the use of animal models to better understand this condition. PMID:23596418

  7. Antidepressant augmentation with anti-inflammatory agents.

    PubMed

    Andrade, Chittaranjan

    2014-09-01

    Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression.

  8. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome

    PubMed Central

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2014-01-01

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress. PMID:24932421

  9. Endovascular treatment for acute pulmonary embolism in neurological patient.

    PubMed

    Paul, Gunchan; Paul, Birinder S; Gautam, Parshotam L; Mohan, Bishav; Sharma, Shruti

    2015-07-01

    Among the spectrum of venous thrombo-embolic disease, acute pulmonary embolism accounts for the most life threatening manifestations with mortality exceeding 50%. It can affect many patient populations across various disciplines, hence immediate attention and aggressive treatment is crucial. With the advancement of technologies, various catheter-based devices are available to treat massive or submassive PE. In this paper we report two patients of acute pulmonary embolism with neurological issues where the life threatening emergency was successfully managed by utilizing endovascular directed thrombolytic reperfusion therapy. PMID:26609298

  10. The future of antidepressants.

    PubMed

    Bourin, M; Baker, G B

    1996-01-01

    A common action of many antidepressants is the inhibition of the reuptake of the biogenic amines norepinephrine, serotonin (5-HT) and/or dopamine into nerve terminals. Another postulated mechanism of action for many antidepressants is the downregulation of beta-adrenergic receptors postsynaptically after chronic administration. Many antidepressants have been reported to produce changes in the regulation of 5-HT1 and 5-HT2 receptors chronically. None of these mechanisms is completely satisfactory as a common antidepressant mechanism of action. Is it possible to unify these hypotheses of antidepressant action? A number of receptor changes have been recognized in depression. Usually, these implicated receptors are linked to a G protein. Thus, it could be hypothesized that depression may be the result of a disorder of the large family of receptor-linked G proteins. Depression, a disorder in which there seems to be an important genetic component, could be expressed in either the receptor or in the G proteins, leading to a defective linkage between the receptor and the G protein, resulting in abnormal transduction mechanisms. The concept of antidepressants is changing rapidly as these agents appear with new therapeutic indications other than depression, such as panic disorder, obsessive compulsive disorder, etc. It can be expected that the presently available antidepressants might eventually be considered anxiolytics or that benzodiazepines and 5-HT1A agonists could come to be viewed as disinhibiting substances.

  11. Antioxidant and antidepressant-like activities of semi-synthetic α-phenylseleno citronellal.

    PubMed

    Victoria, Francine Novack; Anversa, Roberta; Penteado, Filipe; Castro, Micheli; Lenardão, Eder João; Savegnago, Lucielli

    2014-11-01

    In this study, the antioxidant and antidepressant-like activities of the semi-synthetic compound α-phenylseleno citronellal (PhSeCIT) and the natural terpenoid R-citronellal (CIT) were evaluated. The biological potential of PhSeCIT and CIT was evaluated by antioxidant in vitro assays, such as 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric ion reducing antioxidant power (FRAP) and linoleic acid oxidation. The compounds were also assessed by ex vivo tests to determine the acute toxicity, levels of thiobarbituric acid reactive species (TBARS), δ-aminolevulinate dehydratase (δ-Ala-D) and Na(+)/K(+) ATPase activities. The antidepressant-like activity of compounds in the tail suspension test (TST) and forced swimming test (FST) was also investigated. The results demonstrated that the addition of an organoselenium group to (R)-citronellal increased its antioxidant properties, since PhSeCIT showed better activity than CIT. The treatment of mice with both compounds did not cause death of any animals. The levels of TBARS were significantly reduced by PhSeCIT in liver and cortex of animals, whereas CIT did not alter these parameters. In the TST and FST, PhSeCIT showed promising antidepressant-like activity, while CIT was not active in this test. Taken together, these data demonstrate the role of selenium in the antioxidant and antidepressant-like activities of (R)-citronellal.

  12. Inotuzumab ozogamicin in the treatment of acute lymphoblastic leukemia.

    PubMed

    Dahl, Jenny; Marx, Kayleigh; Jabbour, Elias

    2016-01-01

    Over 90% of leukemic blasts in patients with acute lymphoblastic leukemia express the marker CD22. Inotuzumab ozogamicin (INO) is a CD22-directed humanized monoclonal antibody conjugated to the potent cytotoxin, calicheamicin, via an acid labile linker. INO has shown high rates of response in the treatment of relapsed and refractory (R/R) ALL in single-agent studies, with fewer adverse effects than traditional cytotoxic chemotherapy. Given this experience, studies are now being done to evaluate INO in combination with low-intensity chemotherapy as frontline treatment for older adults with ALL and patients with R/R disease. Herein we will discuss the use of INO in the treatment of acute lymphoblastic leukemia.

  13. Current status of mechanical thrombectomy for acute stroke treatment.

    PubMed

    Pereira, Vitor Mendes; Yilmaz, Hasan; Pellaton, Alain; Slater, Lee-Anne; Krings, Timo; Lovblad, Karl-Olof

    2015-02-01

    Acute ischemic stroke is a morbid and disabling medical condition with a significant social and economic impact throughout the world. Intravenous thrombolysis (IVT) has been the first line treatment for patients presenting up to 4.5 hours after symptom onset for many years. Endovascular stroke treatment has been used successfully as rescue therapy after failed IVT; in patients with contraindications to rtPA or presenting outside the 4.5-hour window. The effectiveness of IVT is high for distal thrombi but significantly lower for proximal occlusions. Endovascular treatment has been revolutionized by the evolution from intra-arterial thrombolysis and first generation mechanical devices to the current generation of stent retrievers and aspiration systems with large bore catheters. These devices have been associated with excellent revascularization, improved clinical outcomes, shorter procedure times and reduced device and procedure related complications. We report the current literature, clinical standards and perspectives on mechanical thrombectomy in acute ischemic stroke.

  14. Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression.

    PubMed

    Helmreich, Isabella; Wagner, Stefanie; Mergl, Roland; Allgaier, Antje-Kathrin; Hautzinger, Martin; Henkel, Verena; Hegerl, Ulrich; Tadić, André

    2012-06-01

    In the efficacy evaluation of antidepressant treatments, the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the 'gold standard'. We previously had shown that the Inventory of Depressive Symptomatology (IDS) was more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et al. 2011). Furthermore, studies suggest that the unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo-verum differences. The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding the effect sizes, it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression (e.g. atypical symptoms, sleep disturbances), which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be

  15. Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression.

    PubMed

    Helmreich, Isabella; Wagner, Stefanie; Mergl, Roland; Allgaier, Antje-Kathrin; Hautzinger, Martin; Henkel, Verena; Hegerl, Ulrich; Tadić, André

    2012-06-01

    In the efficacy evaluation of antidepressant treatments, the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the 'gold standard'. We previously had shown that the Inventory of Depressive Symptomatology (IDS) was more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et al. 2011). Furthermore, studies suggest that the unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo-verum differences. The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding the effect sizes, it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression (e.g. atypical symptoms, sleep disturbances), which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be

  16. Treatment of hyperglycaemia in patients with acute stroke.

    PubMed

    Castilla-Guerra, L; Fernández-Moreno, M C; Hewitt, J

    2016-03-01

    The proportion of diabetic patients who are hospitalised for stroke has been increasing in recent years, currently reaching almost a third of all cases of stroke. In addition, about half of patients with acute stroke present hyperglycaemia in the first hours of the stroke. Although hyperglycaemia in the acute phase of stroke is associated with a poor prognosis, its treatment is currently a topic of debate. There is no evidence that the adminstration of intravenous insulin to these patients offers benefits in terms of the evolution of the stroke. New studies in development, such as the SHINE study (Stroke Hyperglycemia Insulin Network Effort), may contribute to clarifying the role of intensive control of glycaemia during the acute phase of the stroke. Ultimately, patients who have presented with stroke should be screened for diabetes. PMID:26189890

  17. Acute low back pain: diagnostics and treatment.

    PubMed

    Becker, F C

    2001-03-01

    How many times have you heard from a patient or groaned yourself "Oh, my aching back?" Innocuous movements such as reaching, stooping, or leaning are halted mid-performance as you sense "something" give, catch, snap, grab, or slide in your lower back. Such subjective complaints may also include sensations of discomfort described as stabbing, sharp, dull, hot/burning, tingling, or numbing. In practice, you will be required to assess these subjective symptoms, effectively document objective data, formulate a diagnosis, and plan appropriate treatment for your patients. Careful attention to history, associated symptoms, and following a systematic approach to back pain can make the rule-in/out differentials less taxing on both the practitioner and the patient.

  18. The Clinical and Cost Effectiveness of Vortioxetine for the Treatment of a Major Depressive Episode in Patients With Failed Prior Antidepressant Therapy: A Critique of the Evidence.

    PubMed

    Lomas, James; Llewellyn, Alexis; Soares, Marta; Simmonds, Mark; Wright, Kath; Eastwood, Alison; Palmer, Stephen

    2016-09-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of vortioxetine (Lundbeck) to submit clinical and cost-effectiveness evidence for vortioxetine for the treatment of major depressive episodes (MDEs), as part of the Institute's Single Technology Appraisal (STA) process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA367 issued in November 2015. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. Two phase III randomised controlled trials for a second-line population involving vortioxetine were identified-REVIVE and TAK318. These two trials represent only 972 of over 7000 patients included in trials of vortioxetine. In REVIVE, there was a statistically significant difference in depression scores favouring vortioxetine compared with agomelatine [mean Montgomery-Åsberg Depression Rating Scale (MADRS) score difference of 2.16 points; 95 % confidence interval 0.81-3.51]. The ERG concluded that, based on all the evidence, rather than the substantially restricted subset of evidence originally considered by the manufacturer, vortioxetine is likely to be similar in efficacy to other analysed antidepressants [citalopram, sertraline, escitalopram and venlafaxine extended release (XR)], and may be more efficacious than agomelatine and inferior to duloxetine. The ERG concluded that vortioxetine may be more tolerable than other analysed antidepressants (sertraline, venlafaxine XR and bupropion), although the limited data prevent firm conclusions. The base-case incremental cost-effectiveness ratio (ICER) of vortioxetine reported by the manufacturer was £378 per quality

  19. Treatment of acute carbon monoxide poisoning with induced hypothermia

    PubMed Central

    Oh, Byoung-Joon; Im, Yong-Gyun; Park, Eunjung; Min, Young-Gi; Choi, Sang-Cheon

    2016-01-01

    Objective The effect of induced hypothermia on severe acute carbon monoxide (CO) poisoning remains to be addressed further. We investigated the effect of induced hypothermia on severe acute CO poisoning. Methods Retrospective chart review was conducted for patients who diagnosed as severe acute CO poisoning in emergency department and underwent induced hypothermia from May 2013 to May 2014. Hospital courses with critical medication and major laboratory results were investigated through the chart review. Results Among total 227 patients with acute CO poisoning during the period of study, patients with severe acute CO poisoning were 15. All patients underwent induced hypothermia with a temperature goal 33°C. Initial and follow-up levels of S100B protein after induced hypothermia were 0.47 μg/L (interquartile range, 0.11 to 0.71) and 0.10 μg/L (interquartile range, 0.06 to 0.37), respectively (P = 0.01). The mean Glasgow Coma Scales at emergency department admission was 6.87 ± 3.36. Except 1 patient who expired after cardiopulmonary resuscitation, Glasgow Coma Scales at 30-day of hospital discharge were 15 in 10 patients (71.4%), 14 in 1 patient (7.1%), 13 in 1 patient (7.1%), and 6 in 2 patients (14.2%). Seven patients (46.7%) developed delayed neurologic sequelae. Four patients showed mild types of delayed neurologic sequelae and 3 showed moderate to severe types of delayed neurologic sequelae. Conclusion Most of patients underwent induced hypothermia had a good recovery from severe acute CO poisoning. Therefore, induced hypothermia may be considered as a possible treatment in severe acute CO poisoning. PMID:27752625

  20. Extreme Response Style in Recurrent and Chronically Depressed Patients: Change with Antidepressant Administration and Stability during Continuation Treatment

    ERIC Educational Resources Information Center

    Peterson, Timothy J.; Feldman, Greg; Harley, Rebecca; Fresco, David M.; Graves, Lesley; Holmes, Avram; Bogdan, Ryan; Papakostas, George I.; Bohn, Laurie; Lury, R. Alana; Fava, Maurizio; Segal, Zindel V.

    2007-01-01

    The authors examined extreme response style in recurrently and chronically depressed patients, assessing its role in therapeutic outcome. During the acute phase, outpatients with major depressive disorder (N = 384) were treated with fluoxetine for 8 weeks. Remitted patients (n = 132) entered a continuation phase during which their fluoxetine dose…

  1. Emerging targets for antidepressant therapies

    PubMed Central

    Rakofsky, Jeffrey J; Holtzheimer, Paul E; Nemeroff, Charles B

    2015-01-01

    Despite adequate antidepressant monotherapy, the majority of depressed patients do not achieve remission. Even optimal and aggressive therapy leads to a substantial number of patients who show minimal and often only transient improvement. In order to address this substantial problem of treatment-resistant depression, a number of novel targets for antidepressant therapy have emerged as a consequence of major advances in the neurobiology of depression. Three major approaches to uncover novel therapeutic interventions are: first, optimizing the modulation of monoaminergic neurotransmission; second, developing medications that act upon neurotransmitter systems other than monoaminergic circuits; and third, using focal brain stimulation to directly modulate neuronal activity. We review the most recent data on novel therapeutic compounds and their antidepressant potential. These include triple monoamine reuptake inhibitors, atypical antipsychotic augmentation, and dopamine receptor agonists. Compounds affecting extra-monoamine neurotransmitter systems include CRF1 receptor antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA receptor antagonists, nemifitide, omega-3 fatty acids, and melatonin receptor agonists. Focal brain stimulation therapies include vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). PMID:19501541

  2. Antidepressant drug use & the risk of suicide.

    PubMed

    Healy, David; Aldred, Graham

    2005-06-01

    There have been longstanding concerns about the propensity of antidepressants to precipitate suicidality in vulnerable individuals. To investigate this further, first we have analyzed all clinical trials, and in particular trials submitted to regulators for evidence on the relative risk of antidepressants versus placebo for this hazard. Second, we have compiled current epidemiological evidence germane to the issue. Third, we have constructed a model (Investigative Medication Routine; IMR) to shed light on the interactions between drug uptake, patient numbers on treatment and suicidal events. The clinical trial data gives rise to a relative risk of suicide on antidepressants over placebo of the order of a 2.0-2.5 times greater risk with treatment. These figures are supported by epidemiological findings. Investigative Medication Routine translates such findings into estimates of likely adverse outcomes, and explains why apparently increasing consumption of antidepressants would not be expected to lead to increased national suicide rates. From this data, we conclude that there is a clear signal that suicides and suicidal acts may be linked to antidepressant usage. It would seem likely that explicit warnings and monitoring in the early stages of treatment could greatly minimize these hazards. PMID:16194787

  3. Re-evaluating the treatment of acute optic neuritis

    PubMed Central

    Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

    2015-01-01

    Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite ‘normal’ (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

  4. 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

  5. A Double-Blind Placebo-Controlled Trial of Maca Root as Treatment for Antidepressant-Induced Sexual Dysfunction in Women

    PubMed Central

    Dording, Christina M.; Schettler, Pamela J.; Dalton, Elizabeth D.; Parkin, Susannah R.; Walker, Rosemary S. W.; Fehling, Kara B.; Fava, Maurizio

    2015-01-01

    Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126. PMID:25954318

  6. A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment.

    PubMed

    Naylor, Jennifer C; Kilts, Jason D; Bradford, Daniel W; Strauss, Jennifer L; Capehart, Bruce P; Szabo, Steven T; Smith, Karen D; Dunn, Charlotte E; Conner, Kathryn M; Davidson, Jonathan R T; Wagner, Henry Ryan; Hamer, Robert M; Marx, Christine E

    2015-05-01

    Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

  7. A double-blind placebo-controlled trial of maca root as treatment for antidepressant-induced sexual dysfunction in women.

    PubMed

    Dording, Christina M; Schettler, Pamela J; Dalton, Elizabeth D; Parkin, Susannah R; Walker, Rosemary S W; Fehling, Kara B; Fava, Maurizio; Mischoulon, David

    2015-01-01

    Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126. PMID:25954318

  8. Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

    PubMed

    Young, Simon N

    2013-03-01

    Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

  9. 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

  10. Antidepressant-Like Effects of Intracerebroventricular FGF2 in Rats

    PubMed Central

    Turner, Cortney A.; Gula, Edny L.; Taylor, Larry P.; Watson, Stanley J.; Akil, Huda

    2008-01-01

    The fibroblast growth factor (FGF) system is altered in post-mortem brains of individuals with major depressive disorder (MDD), but the functional relevance of this observation remains to be elucidated. To this end, we tested whether administering agents that act on FGF receptors would have antidepressant-like effects in rodents. We microinjected either FGF2 (200ng, i.c.v.) or the FG loop (FGL) of neural cell adhesion molecule (NCAM) (5μg, i.c.v.) into the lateral ventricle of rats and tested them on the forced swim test. Activating FGF receptors acutely had an antidepressant-like effect in the forced swim test. Furthermore, chronic FGF2 decreased depression-like behavior as assessed by two independent tests. Finally, the FGF system itself was altered after FGF2 administration. Specifically, there was an increase in FGFR1 mRNA in the dentate gyrus 24 h post FGF2, suggesting the potential for self-amplification of the initial signal. These results support the potential therapeutic use of FGF2 or related molecules in the treatment of MDD and point to alternate mechanisms of neuronal remodeling that may be critical in this treatment. PMID:18586016

  11. 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

  12. Acute otitis media: a simple diagnosis, a simple treatment.

    PubMed

    Chhetri, S S

    2014-09-01

    To assess the symptoms and signs of acute otitis media and efficiency of simple antibiotics like amoxicillin in its treatment in the primary health care setup. This is a prospective longitudinal study including 204 patients from different institutions. Patients were diagnosed as suffering from acute otitis media when presented with earache, fever, fullness and or otorrhea. Patients were divided into two equal groups on basis of the treatment they received, Group A received only symptomatic treatment while Group B were given Amoxicillin (40 mg/kg/day) for 7 days. Acute otitis media was common in children under 15 years (64.7%). Patients presented with earache (100%), aural fullness (90.68%), fever (76.47%) associated with recent onset of upper respiratory tract infections (88.23%). In group A, improvement was noticed in 28.43% in 3 days while 35.29% in 7 days. In group B, improvement was noticed in 48.03% in day 3 while 86.27% in day 7. In countries where medical care is scarce, patients lost to follow up, it is wise to treat with simple antibiotics like amoxicillin in adequate dose than to treat only symptomatically. It prevents chronicity, early hearing impairments and reduces antibiotic resistance.

  13. Acute psychosis associated with dissociated sleep-wakefulness state after mirtazapine treatment.

    PubMed

    Felthous, Alan R; Wenger, Philip J; Hoevet, Rod

    2010-04-01

    Tricyclic antidepressants decrease rapid eye movement (REM) sleep and may suppress sleep atonia. Reports indicate that these agents can induce visual hallucinations, sometimes characterized as hypnopompic or associated with a dissociated sleep-wakefulness state. In addition, disturbing dreams and confusional states were reported during clinical trials and in subsequent studies. To our knowledge, only two cases of nightmares associated with mirtazapine, a tetracyclic antidepressant, have been previously reported. We describe a 43-year-old Caucasian man with major depressive disorder who started mirtazapine 15 mg at bedtime because he had poor symptom control with other antidepressant drugs. Three days later, vivid dream activity was noted, evolving into realistic nightmares that the patient was not able to distinguish from reality on awakening. Acute paranoia was suspected, and haloperidol was started. The dream activity then ended, and within 3 days the patient was able to identify the dreams as unreality. Haloperidol was discontinued, but mirtazapine was continued, and the vivid dream activity persisted; however, reality testing when awake was intact. A short course of haloperidol restored the patient's reality testing, and mirtazapine was eventually replaced with bupropion. The unusual nocturnal activity resolved as a result. Clinicians should be aware of the possible transition from exceptionally vivid dreams to REM sleep behavior disorder and psychosis based on dream content as an adverse effect of mirtazapine.

  14. Treatment-Resistant Depression and Mortality after Acute Coronary Syndrome

    PubMed Central

    Carney, Robert M.; Freedland, Kenneth E.

    2012-01-01

    Depression is a risk factor for morbidity and mortality in patients with coronary heart disease (CHD), especially following acute coronary syndrome (ACS). Evidence from recent clinical trials suggests that treatment-resistant depression may be associated with a particularly high risk of mortality or cardiac morbidity in post-ACS patients. This manuscript reviews this evidence, and considers possible explanations for this relationship. Directions for future research are also considered, with particular emphasis on efforts to elucidate the underlying mechanisms and to develop more efficacious treatments for depression in patients with CHD. PMID:19289455

  15. Treatment of Neuromyelitis Optica Spectrum Disorder: Acute, Preventive, and Symptomatic

    PubMed Central

    Kessler, Remi A.; Mealy, Maureen A.; Levy, Michael

    2016-01-01

    Opinion statement Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that primarily attacks the optic nerves and spinal cord leading to blindness and paralysis. The spectrum of the disease has expanded based on the specificity of the autoimmune response to the aquaporin-4 water channel on astrocytes. With wider recognition of NMOSD, a standard of care for treatment of this condition has condition based on a growing series of retrospective and prospective studies. This review covers the present state of the field in the treatment of acute relapses, preventive approaches, and therapies for symptoms of NMOSD. PMID:26705758

  16. Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures.

    PubMed

    Smaga, Irena; Bystrowska, Beata; Gawliński, Dawid; Pomierny, Bartosz; Stankowicz, Piotr; Filip, Małgorzata

    2014-08-01

    The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery. PMID:24652522

  17. The use of amisulpride in the treatment of acute psychosis

    PubMed Central

    Nuss, Philippe; Hummer, Martina; Tessier, Cédric

    2007-01-01

    The management of acute episodes in schizophrenia is frequently initiated in the psychiatric emergency department and requires rapid intervention to relieve distress and psychiatric symptoms. Both non-pharmacological and pharmacological interventions are needed to calm the patient and prevent potential harm to the patient or others. Treatment is a step-by-step process including management of behavioral symptomatology, diagnosis of potential organic causes, and evaluation of potential substance abuse. Better care is delivered if predefined standard operating procedures are adopted systematically. The ultimate goal of treatment is to establish a therapeutic alliance with the patient. Atypical antipsychotics given orally are recommended as a first-line treatment. As the treatment endpoint is calmness rather than sleep, a non-sedative antipsychotic agent is usually preferred. Drug tolerance is a major issue for the patient. Amisulpride is an effective atypical antipsychotic agent in this context. The optimal dose is 800 mg/day, which is effective on positive and negative symptoms and can be given from the first day with a low risk of extrapyramidal symptoms. Since drug–drug interactions are limited, agitation and anxiety may be controlled by short-term adjunctive therapy with benzodiazepines. In conclusion, amisulpride is an appropriate first-line treatment for the management of acute psychosis. PMID:18360610

  18. Implementing guidelines for the treatment of acute otitis media.

    PubMed

    Barenkamp, Stephen J

    2006-01-01

    The recently published Clinical Practice Guideline for the Diagnosis and Management of Acute Otitis Media represents a sincere effort by the AAP andthe AAFP to provide management guidelines for the practitioner based upon the best scientific evidence available. Despite many years of research and hundreds of clinical studies addressing various aspects of the epidemiology, clinical presentation, and treatment of acute otitis media, important questions remain unaddressed or have been addressed in a less than optimal fashion. These gaps in knowledge and deficiencies in several of the studies that formed the scientific basis for the proposed guidelines are the major reasons behind continued disagreement over certain recommendations. Until more comprehensive and careful analyses can be performed, disagreements are likely to persist. Even so, there is general agreement about most of the recommendations made in these guidelines, and these recommendations will provide a very valuable framework for the practicing physician as he or she cares for children with acute otitis media. To briefly review the major points, first is the critical importance of accurately diagnosing acute otitis media using a combination of clinical findings and observable abnormalities of the tympanic membrane and middle ear space. Particularly important is the differentiation of acute otitis media from otitis media with effusion. Second is the value of treating the pain associated with acute otitis media as a regular component of care, irrespective of any decision concerning antimicrobial treatment. Third is the option, for a select group of older patients with nonsevere disease, of withholding antimicrobial therapy for the first 48 to 72 hours, if close follow-up and active parental involvement can be guaranteed. Fourth is the recommendation that if an antimicrobial agent is used, high-dose amoxicillin (80 to 90 mg/kg/d) is the treatment of choice for most children at the time of initial presentation

  19. Topical Nepafenac in Treatment of Acute Central Serous Chorioretinopathy

    PubMed Central

    Alkin, Zeynep; Osmanbasoglu, Ozen Ayranci; Ozkaya, Abdullah; Karatas, Gonul; Yazici, Ahmet Taylan

    2013-01-01

    This study had been performed to investigate the anatomic and functional outcomes of nepafenac 0.1% therapy in acute central serous chorioretinopathy (CSC). The medical records of 30 patients with acute CSC were reviewed for a total of 31 eye charts. Seventeen eye records of 16 patients who were treated with topical nepafenac 0.1% three times daily for four weeks and continued until complete resolution of subretinal fluid were appraised. Fourteen patients with acute CSC (a total of 14 eye records) who did not receive treatment served as the control group also had been recorded. The proportion of eyes with complete resolution of subretinal fluid, serial changes in the mean best corrected visual acuity (BCVA), and the mean central foveal thickness (CFT) at 6 months of therapy were the outcomes measured. Mean age was 42.6±8.2 years in the treatment group and 41.1±7.1 years in the control group (p=0.85). At 6 months, 14 eyes (82.3%) in the treatment group and 6 eyes (42.8%) in the control group revealed a complete resolution in the subretinal fluid (p=0.02). In the treatment group, mean BCVA (LogMAR) significantly improved from 0.19±0.17 at baseline to 0.09±0.12 at 6 months (p=0.01). In the control group, mean BCVA (LogMAR) was 0.13±0.14 at baseline and decreased to 0.1±0.11 at 6 months (p=0.28). In the treatment group, mean CFT was 349±115 µm at baseline and significantly improved to 221±95 µm at 6 months (p<0.01). In the control group, mean CFT declined from 391±138 µm at baseline to 301±125 µm at 6 months (p=0.06). No treatment-related ocular or systemic side effects were observed. In conclusion, nepafenac 0.1% has the potential to treatment acute CSC. Further trials are warranted to study its safety and efficacy for this disease. PMID:24822228

  20. Continuous morphine produces more tolerance than intermittent or acute treatment.

    PubMed

    Dighe, Shveta V; Madia, Priyanka A; Sirohi, Sunil; Yoburn, Byron C

    2009-05-01

    Dosing protocol and analgesic efficacy have been proposed to be important determinants of the magnitude of opioid tolerance. The present study examined the effect of acute, intermittent and continuous treatment with the low analgesic efficacy agonist morphine on analgesic tolerance. Mice were implanted s.c. with a 25 mg morphine pellet for 1-7 days. Other mice were implanted s.c. with two 25 mg, or one 75 mg morphine pellet for 7 days. The release of morphine from subcutaneous implanted pellets was quantitated using a spectrophotometric assay. In other studies, mice were injected with morphine once (18.5-185 mg/kg/day; approximately 10-100 times ED(50) for morphine analgesia) or once/day for 7 days. Controls were implanted with a placebo pellet or injected with saline. Analysis of drug release from a 25 mg pellet indicated that release was greatest during the first 24 h, declined and then remained relatively constant. The amount of morphine released over 7 days by a 75 mg pellet (23.9 mg) was more than that of a single 25 mg pellet (15.4 mg) but less than two 25 mg pellets (30.8 mg). Following treatment, morphine cumulative dose-response studies were conducted (tail flick). Continuous treatment with morphine using pellet implantation produced a dose-dependent shift in the morphine ED(50) by 3.3, 5.8 and 8.5 fold for one 25 mg pellet, one 75 mg pellet and two 25 mg pellets, respectively. Acute and intermittent morphine administration produced substantially less analgesic tolerance than continuous release of morphine by implant pellets. The maximum shift in the ED(50) was 1.6 for acute treatment and 2.7 for 7 day intermittent treatment; despite a larger total daily dose. The present results indicate that continuous treatment with morphine results in greater analgesic tolerance than acute or intermittent morphine treatment even at comparable daily doses. These results are consistent with the suggestion that intermittent dosing has reduced risk of producing opioid

  1. Treatment of Orbital Complications Following Acute Rhinosinusitis in Children

    PubMed Central

    Wan, Yuzhu; Shi, Guanggang; Wang, Haibo

    2016-01-01

    Background: The orbital complications account for about 80% of all complications secondary to acute rhinosinusitis. If the treatment is not correct and in time, orbital complications could progress rapidly, leading to optic neuritis, cavernous sinus thrombophlebitis or life-threatening intracranial complications. Aims: To evaluate the therapeutic efficacy of conservative therapy for the patients with orbital cellulitis and endoscopic sinus surgery (ESS) performed on patients with subperiosteal abscess (SPA) secondary to acute rhinosinusitis in children. Study Design: Retrospective cross-sectional study. Methods: The retrospective study included 31 pediatric patients with orbital complications secondary to acute rhinosinusitis. In all cases, intensive treatment was initiated with a combination of oral or intravenous antibiotics, glucocorticoid and gelomyrtol forte after admission. ESS was performed if an improvement in the condition of patients did not occur after 48 hours. However, the patients with orbital SPA, motility disorders of eyeball or decreased vision received ESS immediately within 24 hours. Results: Sixteen patients were cured by conservative therapy and 15 patients by ESS. All of the signs and symptoms disappeared after conservative therapy or ESS. There were no recurrences within the follow-up period of 1 to 8 years. Conclusion: Conservative therapy is an effective method for patients with inflammatory edema and most cases of orbital cellulitis in children. SPA can be cured by ESS.

  2. Treatment of Orbital Complications Following Acute Rhinosinusitis in Children

    PubMed Central

    Wan, Yuzhu; Shi, Guanggang; Wang, Haibo

    2016-01-01

    Background: The orbital complications account for about 80% of all complications secondary to acute rhinosinusitis. If the treatment is not correct and in time, orbital complications could progress rapidly, leading to optic neuritis, cavernous sinus thrombophlebitis or life-threatening intracranial complications. Aims: To evaluate the therapeutic efficacy of conservative therapy for the patients with orbital cellulitis and endoscopic sinus surgery (ESS) performed on patients with subperiosteal abscess (SPA) secondary to acute rhinosinusitis in children. Study Design: Retrospective cross-sectional study. Methods: The retrospective study included 31 pediatric patients with orbital complications secondary to acute rhinosinusitis. In all cases, intensive treatment was initiated with a combination of oral or intravenous antibiotics, glucocorticoid and gelomyrtol forte after admission. ESS was performed if an improvement in the condition of patients did not occur after 48 hours. However, the patients with orbital SPA, motility disorders of eyeball or decreased vision received ESS immediately within 24 hours. Results: Sixteen patients were cured by conservative therapy and 15 patients by ESS. All of the signs and symptoms disappeared after conservative therapy or ESS. There were no recurrences within the follow-up period of 1 to 8 years. Conclusion: Conservative therapy is an effective method for patients with inflammatory edema and most cases of orbital cellulitis in children. SPA can be cured by ESS. PMID:27606135

  3. Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels.

    PubMed

    Cigolini, Davide; Ricci, Giogio; Zannoni, Massimo; Codogni, Rosalia; De Luca, Manuela; Perfetti, Paola; Rocca, Giampaolo

    2011-05-24

    Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

  4. Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels.

    PubMed

    Cigolini, Davide; Ricci, Giogio; Zannoni, Massimo; Codogni, Rosalia; De Luca, Manuela; Perfetti, Paola; Rocca, Giampaolo

    2011-09-01

    Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

  5. Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome.

    PubMed

    Bosma, Karen J; Lewis, James F

    2007-09-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening form of respiratory failure that affects a heterogeneous population of critically ill patients. Although overall mortality appears to be decreasing in recent years due to improvements in supportive care, there are presently no proven, effective pharmacological therapies to treat ARDS and prevent its associated complications. The most common cause of death in ARDS is not hypoxemia or pulmonary failure, but rather multiple organ dysfunction syndrome (MODS), suggesting that improving survival in patients with ARDS may be linked to decreasing the incidence or severity of MODS. The key to developing novel treatments depends, in part, on identifying and understanding the mechanisms by which ARDS leads to MODS, although the heterogeneity and complexity of this disorder certainly poses a challenge to investigators. Novel therapies in development for treatment of ALI/ARDS include exogenous surfactant, therapies aimed at modulating neutrophil activity, such as prostaglandin and complement inhibitors, and treatments targeting earlier resolution of ARDS, such as beta-agonists and granulocyte macrophage colony-stimulating factor. From a clinical perspective, identifying subpopulations of patients most likely to benefit from a particular therapy and recognising the appropriate stage of illness in which to initiate treatment could potentially lead to better outcomes in the short term.

  6. [Hereditary angioedema. Treatment of acute attacks in Argentina].

    PubMed

    Malbrán, Alejandro; Malbrán, Eloisa; Menéndez, Alejandra; Fernández Romero, Diego S

    2014-01-01

    In the world, hereditary angioedema (HAE) affects 1 every 50000 persons. It is characterized by highly disabling and recurrent episodes of cutaneous, abdominal and laryngeal episodes of angioedema. Asphyxia related mortality ranges from 15 to 50%. In Argentina a plasma derived C1 inhibitor concentrate (pdC1INH) has been available for the treatment of acute attacks for many decades, however, only15 (26%) out of 58 patients had received pdC1INH at least once until 2008, and only2 (3.4%) had used it regularly. After worldwide approval of the new drugs for the treatment of acute HAE attacks, adding icatibant to pdC1INH in Argentina, and after publication of the therapeutic guide for the country, 42 (82%) out of 51 patients from the original group has pdC1INH available to treat their next attack. However, 16 (18%) patients continue without access to medication and other 15 (35.7%) obtain their therapy spuriously through some other affected relative in their environment. Only 12 (28.6%) patients of the group self-treated at home. Access to treatment has greatly improved, but needs to be extended to all patients and self-treatment at home should be encouraged.

  7. Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment

    PubMed Central

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven

    2014-01-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  8. [Present-day approach to pharmacological and clinical aspects of novel antidepressants].

    PubMed

    Danileviciūte, Vita; Sveikata, Audrius

    2002-01-01

    Depression is the most common illness that affects a large number of individuals in all countries. Recent evidence suggest that depressive episodes if left untreated may heighten severity of subsequent episodes and may increase need for more health care resources. The first antidepressants, tricyclics and monoamine oxidase inhibitors, became available in the late 1950s. A progressive tightening of requirements by drug licensing authorities has ensured that efficacy evidence is good for most antidepressants that are in use. Contemporary antidepressant classification system is based on the mechanism of action, which is presumed to be responsible for their antidepressant effects. A pharmacodynamic system of classification has advantages because it incorporates the current theories of disease pathophysiology. Understanding the basic aspects of mechanism of action of antidepressants is important for treatment of depressive episode, for development of augmenting strategies and combining antidepressants with other antidepressants or antipsychotics. Antidepressants as a class of psychotropic medication have the broad range of indications. The choice of initial antidepressant legitimately varies considerably among clinicians and countries. Referring to some differences of recommendations for the first line treatment of depressive episode we suppose that the choice of antidepressant medication must be individualized for a particular patient. Novel antidepressants (SSRI, SNRI, NaSSA, NARI, NDRI and other) are safe and better tolerated. Metabolism of novel antidepressants is much improved compared with MAOIs and TCAs. The combination of antidepressants is an important clinical issue. There are the following principles of combining antidepressants: 1. to combine mechanisms of action not just drugs, 2. to combine antidepressants and to promote pharmacological synergy and tolerability, 3. to use important synergies within the serotonin, noradrenaline and even dopamine

  9. The antidepressant effects of anticholinergic drugs.

    PubMed

    Howland, Robert H

    2009-06-01

    Acetylcholine is a neurotransmitter that is important for communication between neurons and muscle, is involved in direct neurotransmission in the autonomic parasympathetic nervous system, and has been implicated in cognitive processing, arousal, and attention in the brain. The cholinergic-adrenergic hypothesis of mood disorders states that a given affective state might represent a balance between central cholinergic and adrenergic neurotransmitter activity in those areas of the brain regulating moods. According to this hypothesis, depression would be the clinical manifestation of a state of cholinergic dominance, whereas mania would reflect adrenergic dominance. On the basis of this hypothesis, anticholinergic drugs have been investigated as potential treatments for depression, but study results have not shown consistent antidepressant effects. However, the dosage dependency of scopolamine's effect across different studies and the lack of antidepressant effects with other anticholinergic drugs suggest that a specific muscarinic receptor subtype might be most relevant to the potential antidepressant mechanism of action of anticholinergic drugs.

  10. Pathophysiology and Surgical Treatment of Type A Acute Aortic Dissection

    PubMed Central

    Karube, Norihisa; Yasuda, Shota; Miyamoto, Takuma; Matsuki, Yusuke; Isoda, Susumu; Goda, Motohiko; Suzuki, Shinichi; Masuda, Munetaka; Imoto, Kiyotaka

    2016-01-01

    Objectives: We report the pathophysiology and treatment results of type A acute aortic dissection from our 20-year experience. Methods: We studied 673 patients with type A acute aortic dissection who underwent initial treatment from 1994 through July 2014. We divided these patients into two groups. The former group comprised 448 patients from 1994 through 2008, and the latter group comprised 225 patients from 2009 onward, when the current strategy of initial treatment and surgical technique including the early organ reperfusion therapies were established. Results: Women were significantly often presented than men in patients over 60 years of age. Thrombosed-type dissection accounted for more than half in patients over 70 years, and significantly often complicated pericardial effusion and cardiac tamponade than patent type. Malperfusion occurred in 26% of patients. Central repair operations were performed in 579 patients. In-hospital mortality for all patients was 15%, and for the patients who underwent central repair operations was 10%. Former period of operation, malperfusion, and preoperative cardiopulmonary arrest were significant risk factor of in-hospital death. Preoperative left main trunk (LMT) stents were placed in eight patients and superior mesenteric artery (SMA) intervention was performed in five, they were effective to improve the outcome. From 2009 onward, in-hospital mortality was 5.0% and there was no significant risk factor. Conclusion: Surgical results of type A acute aortic dissection were dramatically improved in the past 20 years. Early reperfusion strategy for the patients with malperfusion improved the outcomes. (This article is a translation of Jpn J Vasc Surg 2015; 24: 127–134.)

  11. Treatment of acute non-anion gap metabolic acidosis.

    PubMed

    Kraut, Jeffrey A; Kurtz, Ira

    2015-02-01

    Acute non-anion gap metabolic acidosis, also termed hyperchloremic acidosis, is frequently detected in seriously ill patients. The most common mechanisms leading to this acid-base disorder include loss of large quantities of base secondary to diarrhea and administration of large quantities of chloride-containing solutions in the treatment of hypovolemia and various shock states. The resultant acidic milieu can cause cellular dysfunction and contribute to poor clinical outcomes. The associated change in the chloride concentration in the distal tubule lumen might also play a role in reducing the glomerular filtration rate. Administration of base is often recommended for the treatment of acute non-anion gap acidosis. Importantly, the blood pH and/or serum bicarbonate concentration to guide the initiation of treatment has not been established for this type of metabolic acidosis; and most clinicians use guidelines derived from studies of high anion gap metabolic acidosis. Therapeutic complications resulting from base administration such as volume overload, exacerbation of hypertension and reduction in ionized calcium are likely to be as common as with high anion gap metabolic acidosis. On the other hand, exacerbation of intracellular acidosis due to the excessive generation of carbon dioxide might be less frequent than in high anion gap metabolic acidosis because of better tissue perfusion and the ability to eliminate carbon dioxide. Further basic and clinical research is needed to facilitate development of evidence-based guidelines for therapy of this important and increasingly common acid-base disorder.

  12. WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis.

    PubMed

    Di Saverio, Salomone; Birindelli, Arianna; Kelly, Micheal D; Catena, Fausto; Weber, Dieter G; Sartelli, Massimo; Sugrue, Michael; De Moya, Mark; Gomes, Carlos Augusto; Bhangu, Aneel; Agresta, Ferdinando; Moore, Ernest E; Soreide, Kjetil; Griffiths, Ewen; De Castro, Steve; Kashuk, Jeffry; Kluger, Yoram; Leppaniemi, Ari; Ansaloni, Luca; Andersson, Manne; Coccolini, Federico; Coimbra, Raul; Gurusamy, Kurinchi S; Campanile, Fabio Cesare; Biffl, Walter; Chiara, Osvaldo; Moore, Fred; Peitzman, Andrew B; Fraga, Gustavo P; Costa, David; Maier, Ronald V; Rizoli, Sandro; Balogh, Zsolt J; Bendinelli, Cino; Cirocchi, Roberto; Tonini, Valeria; Piccinini, Alice; Tugnoli, Gregorio; Jovine, Elio; Persiani, Roberto; Biondi, Antonio; Scalea, Thomas; Stahel, Philip; Ivatury, Rao; Velmahos, George; Andersson, Roland

    2016-01-01

    Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics. PMID:27437029

  13. Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

    PubMed

    Rae, C; Furlong, W; Jankovic, M; Moghrabi, Albert; Naqvi, A; Sala, A; Samson, Y; DePauw, S; Feeny, D; Barr, R

    2014-11-01

    Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood. PMID:24393150

  14. Acute treatment of migraine and the role of triptans.

    PubMed

    Freitag, F G

    2001-03-01

    The use of triptans has improved the ability to treat migraine successfully compared with older treatments. Speed of relief, consistency of effect, and good tolerability have been the hallmarks of these agents. All of the currently available triptans have comparable efficacy and tolerability. Variables between the agents may lead to one agent or dose form being preferred over another in various clinical scenarios. The triptans that are forthcoming may improve on these options through enhanced efficacy rates, tolerability, and headache recurrence rates. There exist increasing options for migraine treatment that may further improve the clinical effects of the older and newer triptans through early treatment of migraine at the stages of mild migraine pain, or even during the prodromal phase of the attack. Additionally, recent work suggests that mini-prophylaxis of migraine at the menses is a highly successful treatment option with the triptans. In this age of managed care, providing cost-effective treatment of headache will take on increasing importance. Techniques such as stratification of acute treatments may enhance cost-effective care, whereas ready availability of the triptans may lead to significant improvements in utilization of parameters such as office visits, emergency room treatment, and even hospitalization. PMID:11898508

  15. Morphine in the treatment of acute pulmonary oedema--Why?

    PubMed

    Ellingsrud, C; Agewall, S

    2016-01-01

    Morphine has for a long time, been used in patients with acute pulmonary oedema due to its anticipated anxiolytic and vasodilatory properties, however a discussion about the benefits and risks has been raised recently. A literature search in Medline and Embase using the keywords "pulmonary oedema" OR "lung oedema" OR "acute heart failure" AND "morphine" was performed. A certain vasodilation has been described after morphine administration, but the evidence for this mechanism is relatively poor and morphine-induced anxiolysis may possibly be the most important factor of morphine in pulmonary oedema and therefore some authors have suggested benzodiazepines as an alternative treatment. Respiratory depression seems to be a less relevant clinical problem according to the literature, whereas vomiting is common, which may cause aspiration. In the largest outcome study, based on the ADHERE registry, morphine given in acute decompensated heart failure was an independent predictor of increased hospital mortality, with an odds ratio of 4.8 (95% CI: 4.52-5.18, p<0.001). Other, smaller studies have shown a significant association between morphine administration and mortality, which was lost after adjusting for confounding factors. Morphine is still used for pulmonary oedema in spite of poor scientific background data. A randomised, controlled study is necessary in order to determine the effect--and especially the risk--when using morphine for pulmonary oedema. Since the positive effects are not sufficiently documented, and since the risk for increased mortality cannot be ruled out, one can advocate that the use should be avoided.

  16. Treatment of acute thoracic aortic syndromes using endovascular techniques

    PubMed Central

    Uğuz, Emrah; Canyiğit, Murat; Hıdıroğlu, Mete; Şener, Erol

    2016-01-01

    PURPOSE Acute thoracic aortic syndrome (ATAS) is a novel term to define emergency aortic conditions with common clinical features and challenges. Traditional management of ATAS includes surgical replacement of the aorta and is correlated with high perioperative mortality and morbidity. We aimed to evaluate our experience and outcomes in patients presenting with ATAS, managed by endovascular techniques. METHODS This cohort consisted of 31 consecutive patients (24 males; mean age, 57.5±13.81 years; range, 19–84 years) with acute thoracic aortic pathologies who underwent endovascular repair between January 2011 and January 2015. The study was designed as a retrospective analysis of prospectively maintained data. RESULTS Complicated acute type-B aortic dissection was the most common pathology (35.5%). All aortic stent-grafts (n=37) and dissection stents (n=9) were implanted with 100% procedural success. The overall in-hospital mortality was 9.7%. The mean follow-up duration of patients who were alive at 30 days was 25.9±11.49 months (3–53 months). So far, there have been no late deaths after 30 days. CONCLUSION In the high-risk setting of ATAS, endovascular procedures come forward as novel therapeutic strategies with promising results. Endovascular repair of ATAS can be considered as a first-line treatment alternative under emergency conditions with encouraging results, particularly when conventional surgical repair cannot be implemented due to prohibitive comorbidities. PMID:27113420

  17. [Protocol for the treatment of severe acute pancreatitis with necrosis].

    PubMed

    Barreda, Luis; Targarona, Javier; Rodriguez, César

    2005-01-01

    The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

  18. Antidepressant action of tianeptine is connected with acceleration of serotonin turnover in the synapse: a hypothesis.

    PubMed

    Uzbekov, Marat G

    2009-06-01

    Based on the results of our investigation of patients with anxious depression under the treatment with serotonergic antidepressants with different mechanism of action on serotonin reuptake we, the first time in the literature, propose the hypothesis about neurochemical mechanism of tianeptine action. According to this hypothesis tianeptine not only activates serotonin reuptake into the synaptic ending but also activates its release from the ending into the synaptic cleft thus accelerating serotonin turnover rate in the synapse. Proposed mechanism mainly refers the first, acute phase of its action directed to the normalization of serotonergic neurotransmission.

  19. Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for involvement of the monoaminergic system

    PubMed Central

    Citó, M.C.O.; Silva, M.I.G.; Santos, L.K.X.; Fernandes, M.L.; Melo, F.H.C.; Aguiar, J.A.C.; Lopes, I.S.; Sousa, P.B.; Vasconcelos, S.M.M.; Macêdo, D.S.; Sousa, F.C.F.

    2014-01-01

    Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days) administration of H. gordonii extract (25 and 50 mg/kg, po) to mice exposed to a forced swimming test (FST). Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT) synthesis], NAN-190 (a 5-HT1A antagonist), ritanserin (a 5-HT2A/2C antagonist), ondansetron (a 5-HT3A antagonist), prazosin (an α1-adrenoceptor antagonist), SCH23390 (a D1 receptor antagonist), yohimbine (an α2-adrenoceptor antagonist), and sulpiride (a D2 receptor antagonist). A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems. PMID:25493384

  20. [Biological treatment strategies of depression--psychopharmacology and non-pharmacological methods].

    PubMed

    Hatzinger, Martin

    2010-11-01

    Biological treatment procedures are based on evidence-based guidelines. According to all of them, a correct diagnosis of depression is required before starting therapy. Within recent years many different types of antidepressants have been introduced to the pharmacotherapeutic armamentarium. The "newer" antidepressants were developed with a view to reduced side effects. However, the classes of antidepressants currently available differ little in their antidepressant efficacy, thus, all producing treatment responses of 50 - 75 %. Therefore, the selection of a particular antidepressant for the individual patient depends on various factors: patient's prior experience with medication, concurrent medical conditions that may be worsened by selected antidepressants, concomitant use of non-psychiatric medications that may lead to negative drug-drug interactions, a drug's short and long-term side effects, physician's experience with the medication and patient's history of adherence to medication. Importantly, if the patient does not show any improvement after two to four weeks of treatment with an antidepressant dose at the upper level of the standard dose, it becomes less likely that he will respond to this particular medication later. When a partial or non-response is present, several therapeutic options are available: (1) combining two antidepressants from different classes, (2) switch to new antidepressant from a different or the same pharmacological class and (3) augmentation strategies. For patients who are reluctant to take traditional antidepressants, herbal remedies such as hypericum perforatum (St. John's Wort) provide an alternative for treatment of mild to moderate depression. Besides pharmacological treatment options non pharmacological biological interventions are available. Electroconvulsive therapy and partial sleep deprivation are very effective in the treatment of acute depression. Especially for seasonal affective disorders light therapy is a well

  1. 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

  2. Diagnosis and treatment of acute low back pain.

    PubMed

    Casazza, Brian A

    2012-02-15

    Acute low back pain is one of the most common reasons for adults to see a family physician. Although most patients recover quickly with minimal treatment, proper evaluation is imperative to identify rare cases of serious underlying pathology. Certain red flags should prompt aggressive treatment or referral to a spine specialist, whereas others are less concerning. Serious red flags include significant trauma related to age (i.e., injury related to a fall from a height or motor vehicle crash in a young patient, or from a minor fall or heavy lifting in a patient with osteoporosis or possible osteoporosis), major or progressive motor or sensory deficit, new-onset bowel or bladder incontinence or urinary retention, loss of anal sphincter tone, saddle anesthesia, history of cancer metastatic to bone, and suspected spinal infection. Without clinical signs of serious pathology, diagnostic imaging and laboratory testing often are not required. Although there are numerous treatments for nonspecific acute low back pain, most have little evidence of benefit. Patient education and medications such as nonsteroidal anti-inflammatory drugs, acetaminophen, and muscle relaxants are beneficial. Bed rest should be avoided if possible. Exercises directed by a physical therapist, such as the McKenzie method and spine stabilization exercises, may decrease recurrent pain and need for health care services. Spinal manipulation and chiropractic techniques are no more effective than established medical treatments, and adding them to established treatments does not improve outcomes. No substantial benefit has been shown with oral steroids, acupuncture, massage, traction, lumbar supports, or regular exercise programs. PMID:22335313

  3. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines.

    PubMed

    Cleare, Anthony; Pariante, C M; Young, A H; Anderson, I M; Christmas, D; Cowen, P J; Dickens, C; Ferrier, I N; Geddes, J; Gilbody, S; Haddad, P M; Katona, C; Lewis, G; Malizia, A; McAllister-Williams, R H; Ramchandani, P; Scott, J; Taylor, D; Uher, R

    2015-05-01

    A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made.

  4. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines.

    PubMed

    Cleare, Anthony; Pariante, C M; Young, A H; Anderson, I M; Christmas, D; Cowen, P J; Dickens, C; Ferrier, I N; Geddes, J; Gilbody, S; Haddad, P M; Katona, C; Lewis, G; Malizia, A; McAllister-Williams, R H; Ramchandani, P; Scott, J; Taylor, D; Uher, R

    2015-05-01

    A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made. PMID:25969470

  5. 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

  6. The Safety and Tolerability Profile of Vilazodone, A Novel Antidepressant for the Treatment of Major Depressive Disorder

    PubMed Central

    Liebowitz, Michael; Croft, Harry A.; Kajdasz, Daniel K.; Whalen, Heidi; Gallipoli, Susan; Athanasiou, Maria; Reed, Carol R.

    2011-01-01

    Objective Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD). This report summarizes the safety and tolerability of vilazodone 40 mg/day during short- and long-term treatment of adult MDD. Methods Pooled data from two 8-week, double-blind studies of vilazodone (n = 436) vs placebo (n = 433) and data from one 52-week, open-label study (n = 616, vilazodone only) were analyzed. Patients aged 18-70 with DSM-IV-TR-defined MDD received vilazodone or placebo (8-week studies only) once daily, with food, titrated to 40 mg/day over 2 weeks. Safety and tolerability assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and weight. Results The most common AEs in all studies were diarrhea, nausea, and headache. Vilazodone-associated AEs in the two 8-week studies, defined as an incidence rate of ≥5% in the vilazodone group and at least twice that for placebo, were diarrhea (28.0% vs 9.2%), nausea (23.4% vs 5.1%), and insomnia (6.0% vs 2.1%), with the majority reported as mild to moderate and <5% of those patients requiring concomitant (directed) treatment for these conditions. Discontinuation rates due to AEs were 7.1% (vilazodone) and 3.2% (placebo) in the 8-week studies and 20.7% in the 52-week study. Vilazodone had no clinically significant effects on vital signs, laboratory tests, or electrocardiograms. Conclusion Vilazodone 40 mg/day was well tolerated during short- and long-term MDD treatment in these trials. Safety profiles associated with 8- and 52-week exposure were consistent.

  7. Fluoxetine epigenetically alters the CaMKIIα promoter in nucleus accumbens to regulate ΔFosB binding and antidepressant effects.

    PubMed

    Robison, A J; Vialou, Vincent; Sun, Hao-Sheng; Labonte, Benoit; Golden, Sam A; Dias, Caroline; Turecki, Gustavo; Tamminga, Carol; Russo, Scott; Mazei-Robison, Michelle; Nestler, Eric J

    2014-04-01

    Chronic social defeat stress in mice produces a susceptible phenotype characterized by several behavioral abnormalities consistent with human depression that are reversed by chronic but not acute exposure to antidepressant medications. Recent work in addiction models demonstrates that the transcription factor ΔFosB and protein kinase calmodulin-dependent protein kinase II (CaMKII) are co-regulated in nucleus accumbens (NAc), a brain reward region implicated in both addiction and depression models including social defeat. Previous work has also demonstrated that ΔFosB is induced in NAc after chronic social defeat stress or after chronic antidepressant treatment, wherein it mediates a pro-resilience or antidepressant-like phenotype. Here, using chromatin immunoprecipitation assays, we found that ΔFosB binds the CaMKIIα gene promoter in NAc and that this binding increases after mice are exposed to chronic social defeat stress. Paradoxically, chronic exposure to the antidepressant fluoxetine reduces binding of ΔFosB to the CaMKIIα promoter and reduces CaMKII expression in NAc, despite the fact that ΔFosB is induced under these conditions. These data suggest a novel epigenetic mechanism of antidepressant action, whereby fluoxetine induces some chromatin change at the CaMKIIα promoter, which blocks the ΔFosB binding. Indeed, chronic fluoxetine reduces acetylation and increases lysine-9 dimethylation of histone H3 at the CaMKIIα promoter in NAc, effects also seen in depressed humans exposed to antidepressants. Overexpression of CaMKII in NAc blocks fluoxetine's antidepressant effects in the chronic social defeat paradigm, whereas inhibition of CaMKII activity in NAc mimics fluoxetine exposure. These findings suggest that epigenetic suppression of CaMKIIα expression in NAc is behaviorally relevant and offer a novel pathway for possible therapeutic intervention in depression and related syndromes.

  8. [Treatment of extensive acute radiation burn and its complications].

    PubMed

    Li, Ye-yang; Wang, Jin-lun; Li, Gang; Lin, Wei-hua; Liang, Min; Huang, Jun; Sun, Jing-en

    2013-06-01

    This article reports the treatment of a patient suffered from acute radiation burn covering 41% TBSA, with deep partial-thickness and full-thickness injury, produced by exposure to a large-scale industrial electron accelerator. An open wound began to appear and enlarged gradually 10 weeks after the exposure. Serious wound infection with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, pneumonia, respiratory failure, systemic inflammatory response syndrome, nephropathy and hypoproteinemia developed successively since 3 weeks after the wound formation. Skin grafts failed to survive, resulting in enlargement of the wound. After being treated with proper measures, including parenteral nutrition, respiratory support with a ventilator, appropriate antibiotics, steroid administration for nephropathy, deep debridement for wounds followed by skin grafting, the patient was cured and discharged after undergoing 15 operations in 500 days. The clinical condition of an extensive acute radiation burn is complicated. We should pay close attention to the changes in functions of organs, and strengthen the therapeutic strategies to support the function of organs to reduce the incidence of systemic complications. The control of the infection and the timely and effective repair of the wound are still the key points of the treatment of an extensive local radiation injury.

  9. Glibenclamide for the Treatment of Acute CNS Injury

    PubMed Central

    Kurland, David B.; Tosun, Cigdem; Pampori, Adam; Karimy, Jason K.; Caffes, Nicholas M.; Gerzanich, Volodymyr; Simard, J. Marc

    2013-01-01

    First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide) is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1)-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel) and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis—all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options. PMID:24275850

  10. Antibody-based treatment of acute myeloid leukaemia.

    PubMed

    Mulford, Deborah A; Jurcic, Joseph G

    2004-01-01

    Monoclonal antibodies have become an important treatment modality in cancer therapy. Genetically engineered chimaeric and humanised antibodies have demonstrated activity against a variety of tumours. Whereas the humanised anti-CD33 monoclonal antibody HuM195 has only modest activity against overt acute myeloid leukaemia (AML), it can eliminate minimal residual disease detectable by reverse transcription-polymerase chain reaction in acute promyelocytic leukaemia. High-dose radioimmunotherapy with beta-particle-emitting isotopes targeting CD33, CD45 and CD66 can potentially allow intensification of antileukaemic therapy before bone marrow transplantation. Conversely, alpha-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumour cell kill while sparing surrounding normal cells. Targeted chemotherapy with the anti-CD33-calicheamicin construct gemtuzumab ozogamicin has produced remissions as a single agent in patients with relapsed AML and appears promising when used in combination with standard chemotherapy in the treatment of newly diagnosed AML. PMID:14680472

  11. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes.

    PubMed

    Graham, Garth

    2016-01-01

    In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement.

  12. Pharmacological treatment of acute migraine in adolescents and children.

    PubMed

    Wöber-Bingöl, Çiçek

    2013-06-01

    Migraine is a common disease in children and adolescents. The incidence of migraine has increased alarmingly in the general population during recent decades. Migraine causes considerable individual suffering and impaired quality of life. Therefore, appropriate management is essential. In this article, the treatment of acute migraine in children and adolescents will be reviewed. Only a few randomized controlled studies have been published and high placebo rates are a major problem for proving superiority of active drugs. Generally, acetaminophen (paracetamol) and ibuprofen are accepted as drugs of first choice, even though the evidence is poor for the former and limited for latter. Among 14 studies on triptans in adolescents, 9 showed some superiority over placebo with respect to pain relief and pain freedom, and among 6 studies in children, 5 suggest some superiority over placebo. Sumatriptan nasal spray and zolmitriptan nasal spray have been approved for adolescents in Europe; almotriptan has been approved for adolescents in the USA, as has rizatriptan for patients aged 6-17 years. A recent study demonstrated the efficacy of a fixed combination of sumatriptan and naproxen in adolescents with migraine. In conclusion, evidence for the pharmacological treatment of acute migraine in children is very poor and evidence for adolescents is better but still limited. PMID:23575981

  13. [Clinical study on Qinghouyan lozenge in treatment of acute pharyngitis].

    PubMed

    Yu, Jiao-iiao; Xuan, Zhen-yu; Ruan, Yan; Zhang, Hui-yong; Shi, Ke-hua; Guo, Yu

    2015-01-01

    To evaluate the clinical efficacy and safety of Qinghouyan lozenge in the treatment of acute pharyngitis due to Lung-heat and Yin-deficiency, and compare with Qinghouyan oral Liquid. Totally 144 subjects were enrolled and randomly divided into two groups (72 in the test group and 72 in the control group). The participants in the test group were given Qinghouyan lozenge for 5 days, and those in the control group were given Qinghouyan oral Liquid for 5 days. The effectiveness evaluation indexes were pharyngalgia/odynophagia disappearance rate, overall efficacy of TCM syndromes, TCM syndrome scores, and single syndrome and sign disappearance rate. During the test, the safety was evaluated by vital sign, lab examination indexes and adverse events. The results for the full analysis set showed that the couth disappearance rate, the incidence rate of TCM syndromes, and the throat/uvula congestion disappearance rate of the test group were higher than that of the control group (P < 0.05), with significant differences in the changes in syndrome scores between the two groups (P < 0.05). Altogether 3 adverse events were observed in the test group while 6 adverse events in the control group, without significant differences in the adverse event rate between the two groups (P < 0.05), serious abnormal laboratory examinations and vital signs. In conclusion, Qinghouyan lozenge has better efficacy in treatment of acute pharyngitis due to Lung-heat and Yin-deficiency than Qinghouyan oral liquid, with good safety. PMID:26080572

  14. 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

  15. [Consensus conference on acute bronchiolitis (IV): Treatment of acute bronchiolitis. Review of scientific evidence].

    PubMed

    González de Dios, J; Ochoa Sangrador, C

    2010-04-01

    A review of the evidence on treatment of acute bronchiolitis is presented. There is sufficient evidence on the lack of effectiveness of most interventions tested in bronchiolitis. Apart from oxygen therapy, fluid therapy, aspiration of secretions and ventilation support, few treatment options will be beneficial. There are doubts about the efficacy of inhaled bronchodilators (salbutamol or adrenaline), with or without hypertonic saline solution, suggesting that these options should be selectively used as therapeutic trials in moderate-severe bronchiolitis. Heliox and non-invasive ventilation techniques, methylxanthine could be used in cases with respiratory failure, in patients with apnea, and surfactant and inhaled ribavirin in intubated critically ill patients. The available evidence does not recommend the use of oral salbutamol, subcutaneous adrenaline, anticholinergic drugs, inhaled or systemic corticosteroids, antibiotics, aerosolized o intravenous immunoglobulin, respiratory physiotherapy and others (nitric oxide, recombinant human deoxyribonuclease, recombinant interferon, nebulised furosemide and so on).

  16. Acute methyl salicylate toxicity complicating herbal skin treatment for psoriasis.

    PubMed

    Bell, Anthony J; Duggin, Geoffrey

    2002-06-01

    We present an interesting case of salicylism arising from the use of methyl salicylate as part of a herbal skin cream for the treatment of psoriasis. A 40-year-old man became quite suddenly and acutely unwell after receiving treatment from an unregistered naturopath. Methyl salicylate (Oil of Wintergreen) is widely available in many over the counter topical analgesic preparations and Chinese medicated oils. Transcutaneous absorption of the methyl salicylate was enhanced in this case due to the abnormal areas of skin and use of an occlusive dressing. The presence of tinnitus, vomiting, tachypnoea and typical acid/base disturbance allowed a diagnosis of salicylate toxicity to be made. Our patient had decontaminated his skin prior to presentation, limiting the extent of toxicity and was successfully treated with rehydration and establishment of good urine flow.

  17. Biology and treatment of adult acute lymphoblastic leukemia.

    PubMed Central

    Levitt, L; Lin, R

    1996-01-01

    The molecular analysis of acute lymphoblastic leukemia (ALL) has provided exciting insights into the pathogenesis of this disease. This disease is heterogenous and can be subtyped based on chromosomal, immunophenotypic, and structural criteria. The varying prognostic implications of different ALL subtypes markedly influence the treatment decisions in adults. Many patients with T-cell ALL can be cured with chemotherapy alone. In contrast, patients with early B-lineage ALL with certain chromosomal abnormalities, especially the Philadelphia chromosome, do not have durable responses to chemotherapy and should receive a bone marrow transplantation if an HLA-matched donor is available. Recent reports have shown improved results for adults with B-cell ALL (Burkitt's) after intensive alternating cycles of chemotherapy containing high doses of methotrexate and cyclophosphamide. Future clinical and laboratory investigation should lead to the development of novel and possibly more effective treatments specifically tailored for different subsets of ALL. PMID:8775728

  18. [RESULTS OF AN ACUTE THROMBOSIS OF HEMORRHOIDAL NODES TREATMENT].

    PubMed

    Akhmedova, E V

    2015-09-01

    The results of treatment of 182 patients, suffering an acute thrombosis of hemorrhoidal nodes of various severity, were studied. In 93 (51.1%) patients (main group) an active surgical tactics was applied. There were conducted urgent, early and postponed operations. In 89 (48.9%) patients (control group) a conservative-expectant tactic was applied. The patients were operated on in terms of 9 - 10 days after admission to hospital. The terms of operation and the method of hemorrhoidectomy were choosed without taking into account the disease severity. Complications in the main group have occurred in 27 (29%) patients, their stationary treatment have lasted 7 - 11 days. In a control group complications were revealed in 27 (30.3%) patients, their stationary stay have lasted from 9 to 28 days.

  19. Recent advancements of bortezomib in acute lymphocytic leukemia treatment.

    PubMed

    Du, Xiao-Li; Chen, Qi

    2013-01-01

    Although survival rates for acute lymphocytic leukemia (ALL), especially in children, have shown dramatic improvement over time, poor outcomes are still observed in patients who have refractory or relapsed disease after conventional chemotherapy. New therapeutic options are urgently needed. Bortezomib (Velcade, formerly PS-341) is the first proteasome inhibitor approved by the US FDA for the treatment of newly diagnosed multiple myeloma and relapsed/refractory multiple myeloma and mantle cell lymphoma. Although the mechanisms of bortezomib anticancer activity are still not completely understood, it is a new treatment option for patients with refractory or relapsed ALL, particularly when used in combination with conventional chemotherapy or targeted agents. This review summarizes recent advancements in the understanding of the bortezomib molecular mechanism of action in ALL. Understanding of the molecular approaches might help customize cancer chemotherapy for each individual patient, directing the field towards rational therapeutics.

  20. Acute methyl salicylate toxicity complicating herbal skin treatment for psoriasis.

    PubMed

    Bell, Anthony J; Duggin, Geoffrey

    2002-06-01

    We present an interesting case of salicylism arising from the use of methyl salicylate as part of a herbal skin cream for the treatment of psoriasis. A 40-year-old man became quite suddenly and acutely unwell after receiving treatment from an unregistered naturopath. Methyl salicylate (Oil of Wintergreen) is widely available in many over the counter topical analgesic preparations and Chinese medicated oils. Transcutaneous absorption of the methyl salicylate was enhanced in this case due to the abnormal areas of skin and use of an occlusive dressing. The presence of tinnitus, vomiting, tachypnoea and typical acid/base disturbance allowed a diagnosis of salicylate toxicity to be made. Our patient had decontaminated his skin prior to presentation, limiting the extent of toxicity and was successfully treated with rehydration and establishment of good urine flow. PMID:12147116

  1. Pediatric acute otitis media: the case for delayed antibiotic treatment.

    PubMed

    Johnson, Nicholas C; Holger, Joel S

    2007-04-01

    Acute otitis media (AOM) is both a commonly diagnosed condition and a frequent indication for antibiotic use in children. Recent literature suggests that antibiotics are not needed in many children with AOM, as most cases resolve spontaneously without complication. However, a majority of AOM infections in children are still treated with antibiotics. The American Academy of Pediatrics and American Academy of Family Physicians released a guideline for treatment of AOM in children. We review the guideline as well as scientific evidence related to AOM treatment options. We support a set of evidence-based guidelines employing a delayed prescription option for antibiotic therapy in selected children. If used appropriately, these cost-effective guidelines will reduce the amount of antibiotics prescribed, increase parental satisfaction, and may lower rates of antibiotic resistance while producing similar rates of resolution of AOM.

  2. Acute Myeloid Leukemia in Infants: Biology and Treatment

    PubMed Central

    Masetti, Riccardo; Vendemini, Francesca; Zama, Daniele; Biagi, Carlotta; Pession, Andrea; Locatelli, Franco

    2015-01-01

    Children aged 0–2 years (i.e., infants) with acute myeloid leukemia (AML) are a peculiar subgroup of patients in the childhood AML scenario. They present with distinctive biological and clinical characteristics, including a high prevalence of prognostically unfavorable risk factors and an increased susceptibility to therapy-related toxicity. Remarkable improvements have been achieved over the last two decades in the treatment of these patients and their outcome is becoming superimposable to that of the older age groups. In this review, we will focus on peculiarities of this young subgroup of children with AML, describing their clinical presentation, the biology of disease, and factors influencing outcome. Treatment results and toxicity data reported by major collaborative groups are also summarized and compared. PMID:25973412

  3. [The new possibility for the treatment of acute cough].

    PubMed

    Klyachkina, I L

    2015-01-01

    ) can be recommended for the inclusion in the combined treatment of the patients presenting with acute and chronic diseases accompanied by the excretion of viscous and difficult-of-discharge bronchial mucus (such as acute and chronic bronchitis, pneumonia, chronic obstructive pulmonary disease, bronchial asthma with difficulty in sputum discharge, and bronchoectatic disease). PMID:26525480

  4. Antidepressants and testicular cancer

    PubMed Central

    Friedman, Gary D.; Schwalbe, Joan; Achacoso, Ninah; Meng, Maxwell V.; Kroenke, Candyce H.; Habel, Laurel A.

    2014-01-01

    Purpose Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with four years more follow-up and expanded study of these and other antidepressant drugs. Methods In the Kaiser Permanente Medical Care Program in northern California, 906 men with testicular cancer diagnosed August 1996–December 2010 were compared with 38,253 matched controls with race/ethnicity recorded regarding receipt of antidepressant drugs at least two years before diagnosis or control index date. Analyses emphasized duration of use and histological subgroups. Results With control for race/ethnicity and use of other antidepressant drugs, odds ratios (OR) and 95% confidence intervals (CI) for associations with testicular cancer were: fluoxetine 1.22 (0.88–1.71), paroxetine 1.19 (0.78–1.83), and 1.21 (0.92–1.58) for all SSRI’s. There was no statistically significant association with risk of all testicular cancers or their histologic subtypes for any individual drug or for tricyclics or all antidepressants combined except for citalopram with all testicular cancers 2.55 (1.43–4.52) and those of mixed histology 4.36 (1.50–12.68) and nefazodone with embryonal cancers 9.79 (1.85–51.81). These could readily be chance findings in the context of the many analyses that were performed. Duration of use was not associated with risk for the drugs and drug groups with sufficient numbers of exposed cases for analysis. Conclusions We found little evidence to support a testicular carcinogenic effect of fluoxetine, paroxetine, or other antidepressant drugs but a weakly positive association is not ruled out. The signals in prior screening may have been due to chance and/or uncontrolled confounding. PMID:24276357

  5. Recent advances and novel treatment paradigms in acute lymphocytic leukemia

    PubMed Central

    Papadantonakis, Nikolaos; Advani, Anjali S.

    2016-01-01

    This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells. CAR T cells have demonstrated promising results in the relapsed/refractory setting. However, the use of BiTEs and CAR T cells is also associated with a distinct set of adverse reactions that must be taken into account by the treating physician. Apart from the above strategies, the use of other targeted therapies has attracted interest. Namely, the discovery of the Philadelphia (Ph)-like signature in children and young adults with ALL has led to the use of tyrosine kinase inhibitors (TKI) in these patients. The different drugs and strategies that are being tested in the relapsed/refractory ALL setting pose a unique challenge in identifying the optimum sequence of treatment and determining which approaches should be considered for frontline treatment.

  6. Genetic susceptibility for bipolar disorder and response to antidepressants in major depressive disorder.

    PubMed

    Tansey, Katherine E; Guipponi, Michel; Domenici, Enrico; Lewis, Glyn; Malafosse, Alain; O'Donovan, Michael; Wendland, Jens R; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2014-01-01

    The high heterogeneity of response to antidepressant treatment in major depressive disorder (MDD) makes individual treatment outcomes currently unpredictable. It has been suggested that resistance to antidepressant treatment might be due to undiagnosed bipolar disorder or bipolar spectrum features. Here, we investigate the relationship between genetic susceptibility for bipolar disorder and response to treatment with antidepressants in MDD. Polygenic scores indexing risk for bipolar disorder were derived from the Psychiatric Genomics Consortium Bipolar Disorder whole genome association study. Linear regressions tested the effect of polygenic risk scores for bipolar disorder on proportional reduction in depression severity in two large samples of individuals with MDD, treated with antidepressants, NEWMEDS (n=1,791) and STAR*D (n=1,107). There was no significant association between polygenic scores for bipolar disorder and response to treatment with antidepressants. Our data indicate that molecular measure of genetic susceptibility to bipolar disorder does not aid in understanding non-response to antidepressants.

  7. Biomarkers to Predict Antidepressant Response

    PubMed Central

    Cook, Ian A.; Hamilton, Steven P.; Narr, Katherine L.; Toga, Arthur; Hunter, Aimee M.; Faull, Kym; Whitelegge, Julian; Andrews, Anne M.; Loo, Joseph; Way, Baldwin; Nelson, Stanley F.; Horvath, Steven; Lebowitz, Barry D.

    2010-01-01

    During the past several years, we have achieved a deeper understanding of the etiology/pathophysiology of major depressive disorder (MDD). However, this improved understanding has not translated to improved treatment outcome. Treatment often results in symptomatic improvement, but not full recovery. Clinical approaches are largely trial-and-error, and when the first treatment does not result in recovery for the patient, there is little proven scientific basis for choosing the next. One approach to enhancing treatment outcomes in MDD has been the use of standardized sequential treatment algorithms and measurement-based care. Such treatment algorithms stand in contrast to the personalized medicine approach, in which biomarkers would guide decision making. Incorporation of biomarker measurements into treatment algorithms could speed recovery from MDD by shortening or eliminating lengthy and ineffective trials. Recent research results suggest several classes of physiologic biomarkers may be useful for predicting response. These include brain structural or functional findings, as well as genomic, proteomic, and metabolomic measures. Recent data indicate that such measures, at baseline or early in the course of treatment, may constitute useful predictors of treatment outcome. Once such biomarkers are validated, they could form the basis of new paradigms for antidepressant treatment selection. PMID:20963521

  8. "The Effects of Cognitive Behavioral Therapy as an Anti-Depressive Treatment is Falling: A Meta-Analysis": Correction to Johnsen and Friborg (2015).

    PubMed

    2016-03-01

    Reports an error in "The effects of cognitive behavioral therapy as an anti-depressive treatment is falling: A meta-analysis" by Tom J. Johnsen and Oddgeir Friborg (Psychological Bulletin, 2015[Jul], Vol 141[4], 747-768). There are several numerical errors in the flowchart summarizing the selection and exclusion of studies as contained in Figure 1. The correct number of titles not further investigated should be 27,381; abstracts rejected should be 1,181; Excluded, different treatment form should be (94). The errors do not affect the results or conclusions of the study as the final number of meta-analysable studies are the same as originally reported. (The following abstract of the original article appeared in record 2015-20361-001.) A meta-analysis examining temporal changes (time trends) in the effects of cognitive behavioral therapy (CBT) as a treatment for unipolar depression was conducted. A comprehensive search of psychotherapy trials yielded 70 eligible studies from 1977 to 2014. Effect sizes (ES) were quantified as Hedge's g based on the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for Depression (HRSD). Rates of remission were also registered. The publication year of each study was examined as a linear metaregression predictor of ES, and as part of a 2-way interaction with other moderators (Year × Moderator). The average ES of the BDI was 1.58 (95% CI [1.43, 1.74]), and 1.69 for the HRSD (95% CI [1.48, 1.89]). Subgroup analyses revealed that women profited more from therapy than did men (p < .05). Experienced psychologists (g = 1.55) achieved better results (p < .01) than less experienced student therapists (g = 0.98). The metaregressions examining the temporal trends indicated that the effects of CBT have declined linearly and steadily since its introduction, as measured by patients' self-reports (the BDI, p < .001), clinicians' ratings (the HRSD, p < .01) and rates of remission (p < .01). Subgroup analyses confirmed that the declining

  9. 77 FR 60126 - Guidance for Industry on Acute Bacterial Otitis Media: Developing Drugs for Treatment; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ...; Formerly 2008N-0004] Guidance for Industry on Acute Bacterial Otitis Media: Developing Drugs for Treatment... Media: Developing Drugs for Treatment.'' This guidance addresses FDA's current thinking regarding the... treatment of acute bacterial otitis media (ABOM). This guidance finalizes the revised draft guidance of...

  10. Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study

    ERIC Educational Resources Information Center

    Kafantaris, Vivian; Coletti, Daniel J.; Dicker, Robert; Padula, Gina; Pleak, Richard R.; Alvir, Jose Ma. J.; Kane, John M.

    2004-01-01

    Objective: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. Method: In this discontinuation study, participants received open treatment with lithium at…

  11. Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia

    PubMed Central

    Joffe, Grigori; Stenberg, Jan-Henry

    2015-01-01

    Background: Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. Methods: To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes. Results: There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors’ efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis. Conclusions: Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups—plausibly due to differences in the mechanisms of action. Antidepressants may not worsen

  12. Treatment of Childhood Acute Lymphoblastic Leukemia Without Prophylactic Cranial Irradiation

    PubMed Central

    Pui, Ching-Hon; Campana, Dario; Pei, Deqing; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Raimondi, Susana C.; Onciu, Mihaela; Coustan-Smith, Elaine; Kun, Larry E.; Jeha, Sima; Cheng, Cheng; Howard, Scott C.; Simmons, Vickey; Bayles, Amy; Metzger, Monika L.; Boyett, James M.; Leung, Wing; Handgretinger, Rupert; Downing, James R.; Evans, William E.; Relling, Mary V.

    2009-01-01

    Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia. PMID:19553647

  13. Gains in employment status following antidepressant medication or cognitive therapy for depression

    PubMed Central

    Fournier, Jay C.; DeRubeis, Robert J.; Amsterdam, Jay; Shelton, Richard C.; Hollon, Steven D.

    2015-01-01

    Background Depression can adversely affect employment status. Aims To examine whether there is a relative advantage of cognitive therapy or antidepressant medication in improving employment status following treatment, using data from a previously reported trial. Method Random assignment to cognitive therapy (n = 48) or the selective serotonin reuptake inhibitor paroxetine (n = 93) for 4 months; treatment responders were followed for up to 24 months. Differential effects of treatment on employment status were examined. Results At the end of 28 months, cognitive therapy led to higher rates of full-time employment (88.9%) than did antidepressant medication among treatment responders (70.8%), χ21 = 5.78, P = 0.02, odds ratio (OR) = 5.66, 95% CI 1.16–27.69. In the shorter-term, the main effect of treatment on employment status was not significant following acute treatment (χ21 = 1.74, P = 0.19, OR = 1.77, 95% CI 0.75–4.17); however, we observed a site×treatment interaction (χ21 = 6.87, P = 0.009) whereby cognitive therapy led to a higher rate of full-time employment at one site but not at the other. Conclusions Cognitive therapy may produce greater improvements in employment v. medication, particularly over the longer term. PMID:24925985

  14. Brain Monoamines and Antidepressant-like Responses in MRL/MpJ Versus C57BL/6J Mice

    PubMed Central

    Balu, Darrick T.; Turner, Jill R.; Brookshire, Bethany R.; Hill-Smith, Tiffany E.; Blendy, Julie A.; Lucki, Irwin

    2013-01-01

    The MRL/MpJ mouse demonstrates enhanced wound healing and tissue regeneration and increased neurotrophic mobilization to chronic antidepressant drug treatments. This study compared brain monoamine systems between MRL/MpJ and C57BL/6J mice as a potential basis for strain differences after chronic antidepressant treatment. MRL/MpJ mice had significantly higher tissue levels of serotonin and dopamine in multiple brain regions. Microdialysis studies demonstrated that baseline levels of extracellular serotonin did not differ between strains. However, acute administration of the selective serotonin reuptake inhibitor citalopram produced an increase in extracellular serotonin in the ventral hippocampus of MRL/MpJ mice that was twice as large as achieved in C57BL/6J mice. The greater effects in MRL/MpJ mice on 5-HT levels were not maintained after local perfusion of citalopram, suggesting that mechanisms outside of the hippocampus were responsible for the greater effect of citalopram after systemic injection. The density of serotonin and norepinephrine transporters in the hippocampus was significantly higher in MRL/MpJ mice. In addition, the expression of 5-HT1A mRNA was lower in the hippocampus, 5-HT1B mRNA was higher in the hippocampus and brain stem and SERT mRNA was higher in the brain stem of MRL/MpJ mice. The exaggerated neurotransmitter release in MRL/MpJ mice was accompanied by reduced baseline immobility in the tail suspension test and a greater reduction of immobility produced by citalopram or the tricyclic antidepressant desipramine. These data suggest that differences in the response to acute and chronic antidepressant treatments between the two strains could be attributed to differences in serotonin or catecholamine transmission. PMID:23220293

  15. The effects of cognitive behavioral therapy as an anti-depressive treatment is falling: A meta-analysis.

    PubMed

    Johnsen, Tom J; Friborg, Oddgeir

    2015-07-01

    A meta-analysis examining temporal changes (time trends) in the effects of cognitive behavioral therapy (CBT) as a treatment for unipolar depression was conducted. A comprehensive search of psychotherapy trials yielded 70 eligible studies from 1977 to 2014. Effect sizes (ES) were quantified as Hedge's g based on the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for Depression (HRSD). Rates of remission were also registered. The publication year of each study was examined as a linear metaregression predictor of ES, and as part of a 2-way interaction with other moderators (Year × Moderator). The average ES of the BDI was 1.58 (95% CI [1.43, 1.74]), and 1.69 for the HRSD (95% CI [1.48, 1.89]). Subgroup analyses revealed that women profited more from therapy than did men (p < .05). Experienced psychologists (g = 1.55) achieved better results (p < .01) than less experienced student therapists (g = 0.98). The metaregressions examining the temporal trends indicated that the effects of CBT have declined linearly and steadily since its introduction, as measured by patients' self-reports (the BDI, p < .001), clinicians' ratings (the HRSD, p < .01) and rates of remission (p < .01). Subgroup analyses confirmed that the declining trend was present in both within-group (pre/post) designs (p < .01) and controlled trial designs (p = .02). Thus, modern CBT clinical trials seemingly provided less relief from depressive symptoms as compared with the seminal trials. Potential causes and possible implications for future studies are discussed. (PsycINFO Database Record

  16. Severe Acute Axonal Neuropathy following Treatment with Arsenic Trioxide for Acute Promyelocytic Leukemia: a Case Report

    PubMed Central

    Kühn, Marcus; Sammartin, Kety; Nabergoj, Mitja; Vianello, Fabrizio

    2016-01-01

    Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences. We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up. Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide. PMID:27158436

  17. [Surgical treatment of acute deep leg and pelvic vein trombosis].

    PubMed

    Gall, F; Husfeldt, K J

    1977-08-25

    In the last 3 years 93 cases of iliofermoral trombosis were treated by surgery. We prefer the method used by Brunner, but under general anaesthesia and using a Bentley-Autotransfusion-System (ATS). The average age of our patients was 55 years (age ranged between 17 and 87 years). No lethal pulmonary embolism was observed. 2, 1 percent of the patients died following apoplex or acute heart failure. Of 67 patients who were operated on 6 months ago or more 70 percent have no further complaints, 28 percent still have some residual edema and only 2 patients have a severe postthrombotic syndrome. 50 percent of 40 control-phlebograms demonstrated patency of all veins. 20 percent had short segmentary occlusions with definite signs of recanalisation, while in 27 percent of the cases occlusions of the lower leg and thigh were found, the iliac veins being free. Only 2 postoperative phlebograms showed a complete iliofemoral venous occlusion. Our results prove, that the operative thrombectomy is a successful method, with which the main complications of the iliofemoral thrombosis-pulmonary embolisation and postthrombotic syndrome-can difinitely be reduced. Also because of better long term results, the operative therapy of acute ilofemoral thrombosis should be generally prefered instead of conservative treatment.

  18. [Acute pancreatitis: guideline-based diagnosis and treatment].

    PubMed

    Tuennemann, J; Mössner, J; Beer, S

    2014-09-01

    Acute pancreatitis is most frequently of biliary or alcoholic origin and less frequently due to iatrogenic (ERCP, medication) or metabolic causes. Diagnosis is usually based on abdominal pain and elevation of serum lipase to more than three-times the normal limit. Acute pancreatitis can either resolve quickly following an oedematous swelling or present as a severe necrotizing form. A major risk is the systemic inflammatory response syndrome (SIRS), which can cause multi-organ failure. Prediction of disease course is initially difficult, thus necessitating immediate therapy and regular re-evaluation. In order to prove or exclude biliary genesis, abdominal ultrasonography should first be performed and endoscopic ultrasound may also be required. Primary therapy includes rapid and correctly dosed fluid substitution. Biliary pancreatitis requires causal treatment. In the case of cholangitis, stone extraction must be performed immediately; in the absence of cholangitis, it might be advisable to wait for spontaneous stone clearance. Timely cholecystectomy is necessary in all cases of biliary pancreatitis. PMID:25139706

  19. 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

  20. 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.

  1. A translational rodent assay of affective biases in depression and antidepressant therapy.

    PubMed

    Stuart, Sarah A; Butler, Paul; Munafò, Marcus R; Nutt, David J; Robinson, Emma Sj

    2013-08-01

    The subjective measures used to study mood disorders in humans cannot be replicated in animals; however, the increasing application of objective neuropsychological methods provides opportunities to develop translational animal tasks. Here we describe a novel behavioral approach, which has enabled us to investigate similar affective biases in rodents. In our affective bias test (ABT), rats encounter two independent positive experiences--the association between food reward and specific digging substrate--during discrimination learning sessions. These are performed on separate days under either neutral conditions or during a pharmacological or affective state manipulation. Affective bias is then quantified using a preference test where both previously rewarded substrates are presented together and the rat's choices recorded. The absolute value of the experience is kept consistent and all other factors are counterbalanced so that any bias at recall can be attributed to treatment. Replicating previous findings from studies in healthy volunteers, we observe significant positive affective biases following acute treatment with typical (fluoxetine, citalopram, reboxetine, venlafaxine, clomipramine) and atypical antidepressants (agomelatine, mirtazapine), and significant negative affective biases following treatment with drugs associated with inducing negative affective states in humans (FG7142, rimonabant, 13-cis retinoic acid). We also observed that acute psychosocial stress and environmental enrichment induce significant negative and positive affective biases, respectively, and provide evidence that these affective biases involve memory consolidation. The positive and negative affective biases induced in our test also mirror the antidepressant and pro-depressant effects of these drugs in patients suggesting our test has both translational and predictive validity. Our results suggest that cognitive affective biases could contribute to drug- or stress-induced mood changes

  2. A translational rodent assay of affective biases in depression and antidepressant therapy.

    PubMed

    Stuart, Sarah A; Butler, Paul; Munafò, Marcus R; Nutt, David J; Robinson, Emma Sj

    2013-08-01

    The subjective measures used to study mood disorders in humans cannot be replicated in animals; however, the increasing application of objective neuropsychological methods provides opportunities to develop translational animal tasks. Here we describe a novel behavioral approach, which has enabled us to investigate similar affective biases in rodents. In our affective bias test (ABT), rats encounter two independent positive experiences--the association between food reward and specific digging substrate--during discrimination learning sessions. These are performed on separate days under either neutral conditions or during a pharmacological or affective state manipulation. Affective bias is then quantified using a preference test where both previously rewarded substrates are presented together and the rat's choices recorded. The absolute value of the experience is kept consistent and all other factors are counterbalanced so that any bias at recall can be attributed to treatment. Replicating previous findings from studies in healthy volunteers, we observe significant positive affective biases following acute treatment with typical (fluoxetine, citalopram, reboxetine, venlafaxine, clomipramine) and atypical antidepressants (agomelatine, mirtazapine), and significant negative affective biases following treatment with drugs associated with inducing negative affective states in humans (FG7142, rimonabant, 13-cis retinoic acid). We also observed that acute psychosocial stress and environmental enrichment induce significant negative and positive affective biases, respectively, and provide evidence that these affective biases involve memory consolidation. The positive and negative affective biases induced in our test also mirror the antidepressant and pro-depressant effects of these drugs in patients suggesting our test has both translational and predictive validity. Our results suggest that cognitive affective biases could contribute to drug- or stress-induced mood changes

  3. Tianeptine in an experimental medicine model of antidepressant action.

    PubMed

    Cooper, Charlotte M; Whiting, Daniel A; Cowen, Philip J; Harmer, Catherine J

    2015-05-01

    Changes in emotional processing have been shown following acute administration of a range of monoaminergic antidepressants, and may represent an important common neuropsychological mechanism underpinning their therapeutic effects. Tianeptine is an agent that challenges the traditional monoaminergic hypothesis of antidepressant action, though its exact mode of action remains controversial. Healthy volunteers were randomised to receive a single dose of tianeptine (12.5 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory and attentional vigilance, as well as working and verbal memory. Tianeptine-treated subjects were less accurate at identifying facial expressions, though this was not valence specific. The tianeptine group also showed reduced positive affective memory and reduced attentional vigilance to positive stimuli. There were no effects on emotional categorization or non-emotional cognition. The negative biases in aspects of emotional processing observed following acute tianeptine administration are at variance with the positive biases generally seen after acute administration of conventional antidepressant drugs, despite tianeptine's putative antidepressant efficacy. This is an intriguing finding in the context of the lack of consensus regarding tianeptine's mechanism of action; however, it may be consistent with the reported ability of acute tianeptine to increase the re-uptake of serotonin.

  4. Tianeptine in an experimental medicine model of antidepressant action.

    PubMed

    Cooper, Charlotte M; Whiting, Daniel A; Cowen, Philip J; Harmer, Catherine J

    2015-05-01

    Changes in emotional processing have been shown following acute administration of a range of monoaminergic antidepressants, and may represent an important common neuropsychological mechanism underpinning their therapeutic effects. Tianeptine is an agent that challenges the traditional monoaminergic hypothesis of antidepressant action, though its exact mode of action remains controversial. Healthy volunteers were randomised to receive a single dose of tianeptine (12.5 mg) or placebo, and subsequently completed a battery of tasks measuring emotional processing, including facial expression recognition, emotional memory and attentional vigilance, as well as working and verbal memory. Tianeptine-treated subjects were less accurate at identifying facial expressions, though this was not valence specific. The tianeptine group also showed reduced positive affective memory and reduced attentional vigilance to positive stimuli. There were no effects on emotional categorization or non-emotional cognition. The negative biases in aspects of emotional processing observed following acute tianeptine administration are at variance with the positive biases generally seen after acute administration of conventional antidepressant drugs, despite tianeptine's putative antidepressant efficacy. This is an intriguing finding in the context of the lack of consensus regarding tianeptine's mechanism of action; however, it may be consistent with the reported ability of acute tianeptine to increase the re-uptake of serotonin. PMID:25759404

  5. Topical vs. systemic treatments for acute otitis media.

    PubMed

    Thornton, Kathy; Parrish, Francie; Swords, Christine

    2011-01-01

    Acute otitis media (AOM) is a common condition in children that is often treated with systemic antibiotic therapy; however, research suggests that non-complicated AOM will resolve spontaneously using only eardrops. To determine best practice for the use of systematic antibiotics compared to topical treatment of AOM, a systematic review of evidence was conducted. Cochrane, Medline, CINAHL, and other databases were searched. Inclusion criteria were studies published from 1995-2010 that included children with AOM and were randomized controlled trials (RCTs). Five systematic reviews and five RCTs were included in the review. Current evidence recommends using topical and other alternative approaches for treating non-complicated AOM in children 2 years of age or older; however, many practitioners are not currently following these recommendations for various reasons. Additional research to address these reasons may help determine how to improve practitioner adherence to best practice evidence and guidelines to help reduce the unnecessary use of systemic antibiotics.

  6. Dilemmas in primary care: antibiotic treatment of acute otitis media.

    PubMed

    True, B L; Helling, D K

    1986-09-01

    Antibiotic treatment of acute otitis media (AOM) accounts for a significant number of all antibiotic prescriptions each year. In the primary care setting, initial antibiotic selection is rarely based on direct evidence, such as cultures of middle ear fluid. Initial antibiotic therapy by the primary care practitioner involves the evaluation and application of information related to prevalence of infecting organisms; in vitro antibiotic spectrum and penetration into middle ear fluid; initial cure rate, relapse and recurrence rates; and antibiotic cost, safety, and convenience. The influence of these factors on the initial antibiotic choice for AOM is reviewed. Several therapeutic dilemmas confronting the prescriber are discussed and a rational approach to initial antibiotic therapy is presented.

  7. Sapacitabine in the treatment of acute myeloid leukemia.

    PubMed

    Norkin, Maxim; Richards, Ashley I

    2015-01-01

    Prognosis of elderly patients with acute myeloid leukemia (AML) remains poor and new treatment approaches are urgently needed. A novel nucleoside analog sapacitabine has recently emerged as a feasible agent because of its oral administration and acceptable toxicity profile. Clinical efficacy of sapacitabine, both as a single agent and in combination, has been evaluated in elderly AML patients or AML patients unfit for standard intensive chemotherapy. Response rates varied from 15 to 45% in phase II studies. Sapacitabine was overall well-tolerated with gastrointestinal and myelosuppression-related complications were the most common side effects. Unfortunately, in a phase III study sapacitabine showed no clinical superiority as compared to low-dose cytarabine (LDAC) in patients with AML. Another large phase III study comparing the combination of sapacitabine with decitabine to decitabine alone is currently ongoing and is expected to be completed by the end of 2015 or by the first half of 2016.

  8. [Current developments in the treatment of acute generalised peritonitis].

    PubMed

    Mitaritonno, M; Perrucci, S; Pellegrini, D; De Tullio, D

    2001-10-01

    Generalised acute peritonitis is a relatively frequently pathology which has always been extremely difficult to treat owing to the large number of complications. Considerable progress has been made over the past few years in the surgical treatment of these pathologies following the introduction of new materials accompanied by new techniques: continuous peritoneal lavage (CPL) and laparostomy are the best known. These techniques must be used in carefully selected patients. They allow a marked improvement in results: fewer cases of redo surgery; fewer local and general complications; shorter hospitalisation stay; fewer deaths. These results are possible because these techniques ensure a better cleansing of the peritoneal cavity, with easier removal of necrotic and purulent materials, the main cause of local and general complications.

  9. High-risk acute myelogenous leukemia: treatment today ... and tomorrow.

    PubMed

    Schiller, Gary J

    2013-01-01

    High-risk acute myelogenous leukemia (AML) constitutes a distinct subset of disease based on clinical and biological characteristics and comprises a significant percentage of all cases of adult AML. Biologic features such as distinct clonal cytogenetic and molecular abnormalities identify a subgroup of AML patients characterized by poor response to induction chemotherapy and poor long-term survival after treatment with consolidation chemotherapy. Clinical variables that predict for poor response include AML relapsed after less than 1 year of remission and AML characterized by resistance to conventional agents. We review here our understanding of the defining biologic subtypes of AML and discuss how adequate initial evaluation can be used to inform the choice of treatment. By defining high-risk biologic and clinical variables, a strong case can be made for treating patients with investigational agents, with treatment directed at distinct cytogenetic or molecular abnormalities. Allogeneic transplantation is the only form of therapy available outside of the setting of a clinical trial that may offer a chance for long-term survival for patients with high-risk AML.

  10. [Peri-interventional management of acute endovascular stroke treatment].

    PubMed

    Schönenberger, S; Bösel, J

    2015-10-01

    Due to the ground breaking consistent evidence that supports the effect of endovascular stroke treatment (EST), many acute care hospitals and stroke centers will have to be prepared to provide this treatment in an optimal way within the coming years. In addition to the intervention itself, patient preparation, stabilization and monitoring during the treatment as well as the aftercare represent significant challenges and have mostly not yet been sufficiently investigated. Under these aspects, the questions of optimal sedation and airway management have received the highest attention. Based on retrospective study results it already seems to be justified, respecting certain criteria, to prefer EST with the patient under conscious sedation (CS) in comparison to general anesthesia (GA) and to only switch to GA in cases of emergency until this question has been clarified by prospective studies. This and other aspects of peri-interventional management, such as logistics, monitoring, blood pressure, ventilation settings, postprocedural steps of intensive or stroke unit care and imaging follow-up are summarized in this overview. The clinical and radiological selection of patients and thus the decision for intervention or technical aspects of the intervention itself will not be part of this article. PMID:26311331

  11. [Intracranial pressure targeted treatment in acute bacterial meningitis increased survival].

    PubMed

    Glimåker, Martin; Johansson, Bibi; Halldorsdottir, Halla; Wanecek, Michael; Elmi-Terander, Adrian; Bellander, Bo-Michael

    2014-12-16

    To evaluate the efficacy of intracranial pressure (ICP)-targeted treatment, compared to standard intensive care, in adults with community acquired acute bacterial meningitis (ABM) and severely impaired consciousness, a prospectively designed intervention-control comparison study was performed. Included were patients with confirmed ABM and severely impaired mental status on admission. Fifty-two patients, given ICP-targeted treatment at a neuro-intensive care unit, and 53 control cases, treated with conventional intensive care, were included. All patients received intensive care with me-chanical ventilation, sedation, antibiotics and corticosteroids according to current guidelines. ICP-targeted treatment was performed in the intervention group, aiming at ICP 50 mmHg. The mortality was significantly lower in the intervention group compared to controls, 5/52 (10%) versus 16/53 (30%). Furthermore, only 17 patients (32%) in the control group fully recovered, compared to 28 (54%) in the intervention group. Early neuro-intensive care using ICP-targeted therapy reduces mortality and improves the overall outcome in adult patients with ABM and severely impaired mental status on admission.

  12. [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

  13. A Model of Placebo Response in Antidepressant Clinical Trials

    PubMed Central

    Rutherford, Bret R; Roose, Steven P.

    2012-01-01

    Placebo response in clinical trials of antidepressant medications is substantial and increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to more failed trials and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for Major Depressive Disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. This review examines contributors to placebo response in antidepressant clinical trials and proposes an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact that enhances treatment response. PMID:23318413

  14. Designing a new generation of antidepressant drugs.

    PubMed

    Pinder, R M

    1997-01-01

    Although longer-term adaptive changes in receptor sensitivity may better explain the delayed onset of action of antidepressants, the mechanism based on acutely elevated noradrenaline (NA) and serotonin (5-HT) synaptic levels remains the basis for new drug design. The dual action concept, which postulates that effects on both NA and 5-HT are more advantageous than a selective action on serotonin reuptake (SSRI), has been used to design new antidepressants such as venlafaxine and mirtazapine. Both drugs enhance NA and 5-HT neurotransmission with little affinity for receptors mediating tricyclic-like side effects. Mirtazapine, the prototype noradrenergic and specific serotonergic antidepressant (NaSSA), specifically enhances 5-HT1 neurotransmission and blocks 5-HT2 and 5-HT3 receptors, and in contrast to venlafaxine lacks SSRI-like and adverse cardiovascular side effects. The unique pharmacological action of mirtazapine is a result of implementation of two concepts: dual action as a basis of efficacy combined with receptor-specific action as a basis of tolerability. PMID:9265946

  15. Antidepressants and Valvular Heart Disease

    PubMed Central

    Lin, Chia-Hui; Hsiao, Fei-Yuan; Liu, Yen-Bin; Gau, Susan Shur-Fen; Wang, Chi-Chuan; Shen, Li-Jiuan

    2016-01-01

    Abstract Empirical evidence regarding the association between antidepressants and valvular heart disease (VHD) is scarce. Using Taiwan's National Health Insurance Research database, this nested case-control study assessed the association between antidepressants and VHD in a Chinese population. Among a cohort of patients who used at least 3 prescription antidepressants, 874 cases with VHD and 3496 matched controls (1:4 ratio) were identified. Conditional logistic regression models were used to examine the timing, duration, dose and type of antidepressants use, and the risk of VHD. Current use of antidepressants was associated with a 1.4-fold increase in the risk of VHD (adjusted odds ratio [aOR] 1.44; 95% confidence interval [CI] 1.17–1.77). Among current users, a dose–response association was observed in terms of the cumulative duration and the cumulative antidepressant dose. Significantly higher risks of VHD were observed among the current users of tricyclic antidepressants (aOR 1.40 [1.05–1.87]). We found that the use of antidepressants was associated with a greater risk of VHD and that the risks varied according to different antidepressants. PMID:27057841

  16. Adherence to antidepressant medications: an evaluation of community pharmacists’ counseling practices

    PubMed Central

    Chong, Wei Wen; Aslani, Parisa; Chen, Timothy F

    2013-01-01

    Background Recent studies have shown that pharmacists have a role in addressing antidepressant nonadherence. However, few studies have explored community pharmacists’ actual counseling practices in response to antidepressant adherence-related issues at various phases of treatment. The purpose of this study was to evaluate counseling practices of community pharmacists in response to antidepressant adherence-related issues. Methods A simulated patient method was used to evaluate pharmacist counseling practices in Sydney, Australia. Twenty community pharmacists received three simulated patient visits concerning antidepressant adherence-related scenarios at different phases of treatment: 1) patient receiving a first-time antidepressant prescription and hesitant to begin treatment; 2) patient perceiving lack of treatment efficacy for antidepressant after starting treatment for 2 weeks; and 3) patient wanting to discontinue antidepressant treatment after 3 months due to perceived symptom improvement. The interactions were recorded and analyzed to evaluate the content of consultations in terms of information gathering, information provision including key educational messages, and treatment recommendations. Results There was variability among community pharmacists in terms of the extent and content of information gathered and provided. In scenario 1, while some key educational messages such as possible side effects and expected benefits from antidepressants were mentioned frequently, others such as the recommended length of treatment and adherence-related messages were rarely addressed. In all scenarios, about two thirds of pharmacists explored patients’ concerns about antidepressant treatment. In scenarios 2 and 3, only half of all pharmacists’ consultations involved questions to assess the patient’s medication use. The pharmacists’ main recommendation in response to the patient query was to refer the patient back to the prescribing physician. Conclusion The

  17. How assess drugs in the treatment of acute bipolar mania?

    PubMed

    Bourin, Michel; Thibaut, Florence

    2013-01-01

    Bipolar affective disorder is a serious mental disease associated with significant morbidity and mortality. Good-quality research available to guide treatment strategies remains insufficient, particularly with regard to manic or hypomanic episodes. A critical review of the various stages of mania might be helpful for pharmaceutical companies and investigators as a prerequisite for the clinical evaluation of potential antimanic properties of medications. The main difficulty is with a comparison between anticonvulsants, antipsychotics, and mood stabilizers such as lithium (with equal efficacy in the acute phase and the prevention of recurrent manic episodes). No consensus has been reached with regard to the treatment of bouts of acute mania in various parts of the world. Controlled clinical trials have, at last, provided irrefutable evidence of the activity of lithium, which has long been used alone, as well as that of divalproate or its derivatives and, to a lesser extent, carbamazepine. The new antipsychotic agents have more recently established their efficacy, especially aripiprazole, asenapine, quetiapine; olanzapine, risperidone, and ziprasidone (not sure where the paradox is). In Europe, haloperidol is still the reference substance used in clinical trials despite the fact that it is not officially indicated in the treatment of mania. In the USA, lithium, divalproate, or antipsychotics can be prescribed as first-line treatment. In Europe, lithium remains the first-line medication, whereas divalproate and atypical antipsychotic agents are used only as second-line therapy. Although both types of medication (antipsychotics, normothymic agents, and/or anticonvulsants) have proved to be clinically effective in the management of mania by reducing the mania scores overall, the same does not apply, however, to all symptoms of mania. Factorial approaches to mania have all shown that since there are several clinical forms of mania, several clusters of manic symptoms can

  18. Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice.

    PubMed

    Moreno, Lina Clara Gayoso E Almendra Ibiapina; Rolim, Hercília Maria Lins; Freitas, Rivelilson Mendes; Santos-Magalhães, Nereide Stela

    2016-09-01

    Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations.

  19. New antiplatelet agents in the treatment of acute coronary syndromes.

    PubMed

    Sabouret, Pierre; Taiel-Sartral, Magali

    2014-03-01

    Effective antagonism of the P2Y12 platelet receptor is central to the treatment of acute coronary syndrome (ACS) patients, especially in the setting of percutaneous coronary intervention and stenting. According to consensus guidelines, early revascularization and intensive antiplatelet therapy are key to reducing the complications that arise from myocardial ischaemia and the recurrence of cardiovascular events. Until recently, clopidogrel was the key P2Y12 antagonist advocated, but due to several limitations as an antiplatelet agent, newer drugs with more predictable, rapid and potent effects have been developed. Prasugrel and ticagrelor are now the recommended first-line agents in patients presenting with non-ST-segment elevation ACS and ST-segment elevation ACS, due to large-scale randomized trials that demonstrated net clinical benefit of these agents over clopidogrel, as stated in the European guidelines. Although no study has directly compared the two agents, analysis of the data to date suggests that certain patient types, such as diabetics, those with ST-segment elevation myocardial infarction or renal failure and the elderly may have a better outcome with one agent over the other. Further studies are needed to confirm these differences and answer pending questions regarding the use of these drugs to optimize efficacy while minimizing adverse events, such as bleeding. The aim of this review is to provide an overview of the current P2Y12 receptor antagonists in the treatment of ACS, with a focus on issues of appropriate agent selection, timing of treatment, bleeding risk and the future role of personalized treatment using platelet function and genetic testing. PMID:24630752

  20. 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

  1. Treatment of acute schizophrenia with paliperidone ER: predictors for treatment response and benzodiazepine use.

    PubMed

    Heres, Stephan; Don, Liana; Herceg, Miroslav; Bidzan, Leszek; Blanc, Michel; Siracusano, Alberto; Maciulis, Valentinas; Lahaye, Marjolein; Schreiner, Andreas

    2014-01-01

    The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed to explore treatment response, tolerability, and safety of flexible doses of paliperidone ER in patients with schizophrenia admitted for an acute exacerbation. This paper addresses a secondary analysis of PERTAIN data designed to explore predictors for treatment response, flexible dosing, and concomitant benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single-arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily) to treat patients hospitalized for an acute exacerbation of schizophrenia, reflecting more closely daily clinical practice. Predictive models were evaluated for paliperidone ER flexible dosing, treatment response, and concomitant treatment with benzodiazepines as distinct independent variables. For the analysis of explanatory variables, a stepwise logistic regression was used, taking into account patient age, gender, body mass index, diagnosis and duration of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS), disease severity (CGI-S), and patient functioning (PSP) at baseline. Early response (defined as response within 2weeks of treatment initiation) was also used as a predictor. Clinical response (defined as ≥30% decrease in PANSS total score and ≥1 point decrease in CGI-S from baseline to endpoint) was predicted by early clinical response (p<0.001) and there was a trend for the diagnosis of paranoid schizophrenia vs. other types of schizophrenia to predict clinical response (p=0.0525). High response (defined as ≥50% decrease in PANSS total score and ≥2 points decrease in CGI-S from baseline to endpoint) was predicted by early high response, higher baseline CGI-S, or female gender. More severely ill patients with a higher baseline CGI-S were twice likely to be treated concomitantly with a benzodiazepine. PMID:24096139

  2. Poor survival of treatment-related acute nonlymphocytic leukemia

    SciTech Connect

    Neugut, A.I. Nieves, J.; Murray, T.; Tsai, Weiyann ); Robinson, E. )

    1990-08-29

    Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients.

  3. Evaluation of artemisinins for the treatment of acute myeloid leukemia

    PubMed Central

    Drenberg, Christina D.; Buaboonnam, Jassada; Orwick, Shelley J.; Hu, Shuiying; Li, Lie; Fan, Yiping; Shelat, Anang A.; Guy, R. Kiplin; Rubnitz, Jeffrey

    2016-01-01

    Purpose Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models. Methods Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts. In vivo pharmacokinetic studies and efficacy of single-agent ART or combination with cytarabine were evaluated in three xenograft models. Results ART and DHA had the most potent activity in a panel of AML cell lines, with selectivity toward samples harboring MLL rearrangements and FLT3-ITD mutations. Combination of ART or DHA was synergistic with cytarabine. Single-dose ART (120 mg/kg) produced human equivalent exposures, but multiple dose daily administration required for in vivo efficacy was not tolerated. Combination treatment produced initial regression, but did not prolong survival in vivo. Conclusions The pharmacology of artemisinins is problematic and should be considered in designing AML treatment strategies with currently available agents. Artemisinins with improved pharmacokinetic properties may offer therapeutic benefit in combination with conventional therapeutic strategies in AML. PMID:27125973

  4. Evaluation and treatment of acute low back pain.

    PubMed

    Kinkade, Scott

    2007-04-15

    Acute low back pain with or without sciatica usually is self-limited and has no serious underlying pathology. For most patients, reassurance, pain medications, and advice to stay active are sufficient. A more thorough evaluation is required in selected patients with "red flag" findings associated with an increased risk of cauda equina syndrome, cancer, infection, or fracture. These patients also require closer follow-up and, in some cases, urgent referral to a surgeon. In patients with nonspecific mechanical low back pain, imaging can be delayed for at least four to six weeks, which usually allows the pain to improve. There is good evidence for the effectiveness of acetaminophen, nonsteroidal anti-inflammatory drugs, skeletal muscle relaxants, heat therapy, physical therapy, and advice to stay active. Spinal manipulative therapy may provide short-term benefits compared with sham therapy but not when compared with conventional treatments. Evidence for the benefit of acupuncture is conflicting, with higher-quality trials showing no benefit. Patient education should focus on the natural history of the back pain, its overall good prognosis, and recommendations for effective treatments. PMID:17477101

  5. Antidepressant-Like Effects of Sanggenon G, Isolated from the Root Bark of Morus alba, in Rats: Involvement of the Serotonergic System.

    PubMed

    Lim, Dong Wook; Jung, Jae-Woo; Park, Ji-Hae; Baek, Nam-In; Kim, Yun Tai; Kim, In-Ho; Han, Daeseok

    2015-01-01

    The root bark of Morus alba is commonly used as an alternative medicine due to its numerous health benefits in humans. However, the antidepressant effects of various active components from M. alba have not been fully elucidated. In this study, we aimed to determine whether sanggenon G, an active compound isolated from the root bark of M. alba, exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with sanggenon G (30 mg/kg, intraperitoneally (i.p.)) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with sanggenon G also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hypothalamic paraventricular nucleus (PVN). In addition, the antidepressant-like effects of sanggenon G were significantly inhibited by WAY100635 (1 mg/kg, i.p.; a selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonist), but not SCH23390 (0.05 mg/kg, i.p.; a dopamine D1 receptor antagonist). Our findings suggested that the antidepressant-like effects of sanggenon G were mediated by an interaction with the serotonergic system. Further studies are needed to evaluate the potential of sanggenon G as an alternative therapeutic approach for the treatment of depression. PMID:26289125

  6. Antidepressant-Like Effects of Sanggenon G, Isolated from the Root Bark of Morus alba, in Rats: Involvement of the Serotonergic System.

    PubMed

    Lim, Dong Wook; Jung, Jae-Woo; Park, Ji-Hae; Baek, Nam-In; Kim, Yun Tai; Kim, In-Ho; Han, Daeseok

    2015-01-01

    The root bark of Morus alba is commonly used as an alternative medicine due to its numerous health benefits in humans. However, the antidepressant effects of various active components from M. alba have not been fully elucidated. In this study, we aimed to determine whether sanggenon G, an active compound isolated from the root bark of M. alba, exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with sanggenon G (30 mg/kg, intraperitoneally (i.p.)) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with sanggenon G also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hypothalamic paraventricular nucleus (PVN). In addition, the antidepressant-like effects of sanggenon G were significantly inhibited by WAY100635 (1 mg/kg, i.p.; a selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonist), but not SCH23390 (0.05 mg/kg, i.p.; a dopamine D1 receptor antagonist). Our findings suggested that the antidepressant-like effects of sanggenon G were mediated by an interaction with the serotonergic system. Further studies are needed to evaluate the potential of sanggenon G as an alternative therapeutic approach for the treatment of depression.

  7. Mirtazapine--another new class of antidepressant.

    PubMed

    1999-01-01

    Mirtazapine (Zispin-Organon) was introduced in 1997 as "the first noradrenergic and specific serotonergic antidepressant" (or 'NaSSA'). The manufacturer claims that mirtazapine is "effective in all types of depression", with "minimal serotonergic, anticholinergic and antiadrenergic side-effects", "low propensity for interactions", and lower likelihood of relapse during maintenance treatment than with amitriptyline. Is mirtazapine an advance on existing drugs? PMID:10562767

  8. Emerging antidepressants to treat major depressive disorder.

    PubMed

    Block, Samantha G; Nemeroff, Charles B

    2014-12-01

    Depression is a common disorder with an annual risk of a depressive episode in the United States of 6.6%. Only 30-40% of patients remit with antidepressant monotherapy, leaving 60-70% of patients who do not optimally respond to therapy. Unremitted depressive patients are at increased risk for suicide. Considering the prevalence of treatment resistant depression and its consequences, treatment optimization is imperative. This review summarizes the latest treatment modalities for major depressive disorder including pharmacotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation and psychotherapy. Through advancements in research to better understand the pathophysiology of depression, advances in treatment will be realized.

  9. 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

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

    PubMed

    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

  11. Cannabinoids, Neurogenesis and Antidepressant Drugs: Is there a Link?

    PubMed Central

    Fogaça, Manoela Viar; Galve-Roperh, Ismael; Guimarães, Francisco Silveira; Campos, Alline Cristina

    2013-01-01

    Similar to clinically used antidepressants, cannabinoids can also regulate anxiety and depressive symptoms. Although the mechanisms of these effects are not completely understood, recent evidence suggests that changes in endocannabinoid system could be involved in some actions of antidepressants. Chronic antidepressant treatment modifies the expression of CB1 receptors and endocannabinoid (EC) content in brain regions related to mood and anxiety control. Moreover, both antidepressant and cannabinoids activate mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase(PI3-K)/Akt or PKB signaling, intracellular pathways that regulate cell proliferation and neural cell survival. Facilitation of hippocampal neurogenesis is proposed as a common effect of chronic antidepressant treatment. Genetic or pharmacological manipulations of cannabinoid receptors (CB1 and CB2) or enzymes responsible for endocannabinoid-metabolism have also been shown to control proliferation and neurogenesis in the hippocampus. In the present paper we reviewed the studies that have investigated the potential contribution of cannabinoids and neurogenesisto antidepressant effects. Considering the widespread brain distribution of the EC system, a better understanding of this possible interaction could contribute to the development of therapeutic alternatives to mood and anxiety disorders. PMID:24179463

  12. [Effect of antidepressive agents on serotonin secretion and membrane potential changes in thrombocytes].

    PubMed

    Pogady, J

    1983-06-01

    Antidepressants (Amitriptylin, Imipramine, Ludiomil, Alival) at the concentrations present in the blood during treatment do not inhibit serotonin secretion by human blood platelets. This also applies for the concentrations at which they are present in the blood during therapy. The same antidepressants do inhibit the changes in membrane potential accompanying serotonin secretion. This suggests that there is a weak interaction between the antidepressants and the secretion mechanism.

  13. Serelaxin a novel treatment for acute heart failure.

    PubMed

    Castrini, Anna Isotta; Carubelli, Valentina; Lazzarini, Valentina; Bonadei, Ivano; Lombardi, Carlo; Metra, Marco

    2015-01-01

    Acute heart failure (AHF) represents a major healthcare burden with a high risk of in-hospital and post-discharge mortality, which remained almost unchanged in the last few decades, underscoring the need of new treatments. Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone and has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. Recently, the new molecule serelaxin, a recombinant form of the naturally occurring hormone relaxin has been studied in patients hospitalized for AHF. In addition to vasodilation, serelaxin has anti-oxidative, anti-inflammatory and connective tissue regulating properties. In preclinical studies, it reduced both systemic and renal vascular resistance and, in the clinical trials Pre-RELAX-AHF and RELAX-AHF, it improved dyspnea and signs of congestion. In addition, serelaxin was associated with a reduction of 180-day mortality. The aim of this review is to summarize the pharmacological properties of serelaxin and the results of the preclinical and clinical studies. PMID:26294074

  14. Technologies for diagnosis and treatment of acute stroke

    SciTech Connect

    Fitch, J.P.

    1998-02-09

    From October 1994 to June 1997, a multidisciplinary team of scientists and engineers at Lawrence Livermore National Laboratory were funded through LDRD to develop and integrate technologies for diagnosis and treatment of acute stroke. The project was summarized in a Science and Technology Review article `Brain Attack` that appeared in June 1997 and again in the Center for Healthcare Technologies Report (UCRL-LR-124761). This article is the best overview of the project, epidemiology of stroke and technical progress. Most of the technical progress has been documented in conference papers and presentations and refereed journal articles. Additional technical publication can be expected as our remaining patent applications progress through the US Patent and Trademark Office. The purpose of this report is to provide an appropriate introduction and organization to the numerous publications so that interested readers can quickly find information. Because there is no documentation for the history of this project, this report provides a summary. It also provides the final status report for the LDRD funding.

  15. [Targets of treatment in the acute phase of cerebral infarction].

    PubMed

    Tanaka, K; Fukuuchi, Y; Nogawa, S; Ito, D; Suzuki, S; Dembo, T; Kosakai, A

    2001-12-01

    In the acute phase of cerebral infarction, many experimental data suggest that free radicals including superoxide, hydroxy radical and nitric oxide are one of the most important factors to cause brain damage. We have clearly detected nitrotyrosine (a marker of endogenous production of peroxynitrite, which is readily produced from superoxide and nitric oxide) in neurons and intraparenchymal vascular walls during post-ischemic reperfusion. Free radical scavengers thus seem to be very promising tools of treatment, and one of them (edaravone) has recently been approved for clinical use in Japan. CREB (cyclic AMP response element binding protein) is a DNA-binding transcription factor, and its function is activated by phosphorylation of Ser133 residue. CREB plays important roles in neuronal development, synaptic plasticity and regeneration. We have found that phosphorylation of CREB is significantly and persistently increased in surviving neurons and oligodendrocytes in post-ischemic brain, while this phosphorylation is only transiently increased in neurons and oligodendrocytes which eventually die. These data suggest that CREB phosphorylation plays an important role in protection of ischemic brain tissue. Oligodendrocyte progenitor cells (OPC) remain abundant throughout the adult brain, and retain their ability to become not only mature oligodendrocytes, but also neurons. We have recently found that OPC are significantly activated and proliferate in the peri-infarct area at 1-2 weeks after ischemia, suggesting that OPC may be involved in the repair mechanisms of ischemic brain. Future targets of stroke treatment should include enhancement of intrinsic protection mechanisms such as CREB phosphorylation and activation of progenitors cells. PMID:12235793

  16. Both acute and chronic buspirone treatments have different effects on regional 5-HT synthesis in Flinders Sensitive Line rats (a rat model of depression) than in control rats

    PubMed Central

    Nishi, Kyoko; Kanemaru, Kazuya; Hasegawa, Shu; Watanabe, Arata; Diksic, Mirko

    2009-01-01

    The main objective of this investigation was to evaluate the effects of buspirone, a 5-HT1A agonist with some partial agonist properties and also an antidepressant, on regional 5-HT synthesis in Flinders Sensitive Line (FSL) rats (“depressed”), and to compare the effects to the Flinders Resistant Line (FRL) control rats (not “depressed”). In addition results were compared to those previously reported in normal Sprague-Dawley (SPD) rats (normal control). Serotonin synthesis in both FSL and FRL rats was measured following acute and chronic treatments with buspirone. Both of these strains were derived from the SPD rats. No direct comparison was done between the FSL saline and FRL saline groups, or the FSL buspirone and FRL buspirone groups, because the objective of the studies was to evaluate effects of buspirone in these two strains. The results show that acute treatment with buspirone elevates 5-HT synthesis throughout the brain in the FRL rats. In the FSL rats, there were reductions in some brain regions (e.g., dorsal and median raphe, amygdala, anterior olfactory nucleus, substantia nigra reticulate), while in other regions, there were increases in the synthesis observed (e.g., frontal, parietal, visual and somatosensory cortices, ventral hippocampus). In twenty out of the thirty brain regions investigated in the FSL rats, there was no significant change in the synthesis following acute buspirone treatment. During the chronic treatment, buspirone produced a significant reduction of 5-HT synthesis in fifteen out of thirty brain regions in the FRL rats. In the FSL rats, buspirone produced a significant elevation of the synthesis in ten out of thirty brain regions. In both the FSL and FRL rats, buspirone produced rather different effects than those reported previously for SPD (normal) rats. The acute effect in the FSL rats was somewhat similar to the effect reported previously for the SPD rats, while in the FRL rats, the acute buspirone treatment produced an

  17. 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 , ...

  18. Unrecognized acute exertional compartment syndrome of the leg and treatment.

    PubMed

    Popovic, Nebojsa; Bottoni, Craig; Cassidy, Charles

    2011-04-01

    Acute-on-chronic exertional compartment syndrome is rare and may be easily missed without a high degree of awareness and clinical suspicion. We report a case of unrecognized acute-on-chronic exertional compartment syndrome in a recreational soccer player. The late sequela of this condition, foot drop, was successfully treated with transfer of the peroneus longus tendon.

  19. Sinus Balloon Dilation as Treatment for Acute Sphenoid Sinusitis with Impaired Vision for a Child.

    PubMed

    Zhao, Yin; Chen, Kangbing; Wang, Zonggui

    2016-01-01

    This paper is about sinus balloon dilatation in treatment of acute left sphenoid sinusitis with left impaired vision in a child. Balloon catheter dilatation (BCD) of the sinus ostia is a new technique. It has been shown to be a minimally invasive technique to manage chronic sinusitis. However, this method is rarely used in the treatment of acute sinusitis. So far, we know of no reported cases of sinus balloon dilatation in treatment of this case, especially for children.

  20. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Schmiegelow, Kjeld; Levinsen, Mette Frandsen; Attarbaschi, Andishe; Baruchel, Andre; Devidas, Meenakshi; Escherich, Gabriele; Gibson, Brenda; Heydrich, Christiane; Horibe, Keizo; Ishida, Yasushi; Liang, Der-Cherng; Locatelli, Franco; Michel, Gérard; Pieters, Rob; Piette, Caroline; Pui, Ching-Hon; Raimondi, Susana; Silverman, Lewis; Stanulla, Martin; Stark, Batia; Winick, Naomi; Valsecchi, Maria Grazia

    2013-01-01

    Purpose Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2 per week and mercaptopurine of at least 75 mg/m2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts. PMID:23690411

  1. Antidepressant-like activity of selective serotonin reuptake inhibitors combined with a NK1 receptor antagonist in the mouse forced swimming test.

    PubMed

    Chenu, F; Guiard, B P; Bourin, M; Gardier, A M

    2006-09-25

    Substance P antagonists of the neurokinin-1 receptor type (NK1) have growing interest as new antidepressant therapies. It has been postulated that these drugs exert this putative therapeutic effect without direct interactions with serotonin (5-HT) neurons. In line with this assumption, previous intracerebral in vivo microdialysis experiments provided evidence that the NK1 receptor antagonists did not change basal cortical 5-HT levels. However, we found that increases in cortical 5-HT overflow caused by systemic injection of the selective serotonin reuptake inhibitor (SSRI), paroxetine was higher in freely moving (C57BL/6x129sv) NK1-/- mutants than in wild-type NK1+/+ mice. More recently, a pharmacological study has led to a similar conclusion since GR205171, a NK1 receptor antagonist, potentiated paroxetine-induced increases in cortical 5-HT dialysate following its acute systemic or intra-raphe administration to wild-type mice . In the present study, we tested whether an acute combination of SSRI and NK1 receptor antagonist could display antidepressant-like activity using the forced swimming test in Swiss mice. We found that a single systemic dose of GR205171 (10 and 30 mg/kg, i.p.) had no effect by itself. However, it selectively potentiated the antidepressant-like activity of subactive doses of two serotonergic antidepressant drugs, citalopram and paroxetine (without psychomotor stimulant activity), but not that of noradrenaline reuptake inhibitor, desipramine. In agreement with neurochemical data, the present study confirms that co-administration of a NK1 receptor antagonist with an antidepressant drug such as a SSRI may have a therapeutic potential to improve the treatment of major depressive episodes in human compared to SSRI alone.

  2. Phosphorylation of MeCP2 at Ser421 contributes to chronic antidepressant action

    PubMed Central

    Hutchinson, Ashley N.; Deng, Jay V.; Cohen, Sonia; West, Anne E.

    2012-01-01

    Although tricyclic antidepressants rapidly activate monoaminergic neurotransmission, these drugs must be administered chronically to alleviate symptoms of depression. This observation suggests that molecular mechanisms downstream of monoamine receptor activation, which include the induction of gene transcription, underlie chronic antidepressant-induced changes in behavior. Here we show that methyl-CpG binding protein 2 (MeCP2) regulates behavioral responses to chronic antidepressant treatment. Imipramine administration induces phosphorylation of MeCP2 at Ser421 (pMeCP2) selectively in the nucleus accumbens and the lateral habenula, two brain regions important for depressive-like behaviors. To test the role of pMeCP2 in depressive-like behaviors, we utilized male mice that bear a germline mutation knocked into the X-linked Mecp2 locus that changes Ser421 to a nonphosphorylatable Ala residue (S421A). MeCP2 S421A knockin (KI) mice showed increased immobility in forced swim and tail suspension tests compared with their wildtype (WT) littermates. However immobility of both MeCP2 WT and KI mice in forced swim was reduced by acute administration of imipramine, demonstrating that loss of pMeCP2 does not impair acute pharmacological sensitivity to this drug. Following chronic social defeat stress, chronic administration of imipramine significantly improved social interaction in the MeCP2 WT mice. By contrast, the MeCP2 KI mice did not respond to chronic imipramine administration. These data suggest novel roles for pMeCP2 in the sensitivity to stressful stimuli and demonstrate that pMeCP2 is required for the effects of chronic imipramine on depressive-like behaviors induced by chronic social defeat stress. PMID:23055506

  3. In vitro antioxidant activity and in vivo antidepressant-like effect of α-(phenylselanyl) acetophenone in mice.

    PubMed

    Gerzson, Mariana Freire Barbieri; Victoria, Francine N; Radatz, Cátia S; de Gomes, Marcelo G; Boeira, Silvana P; Jacob, Raquel G; Alves, Diego; Jesse, Cristiano Ricardo; Savegnago, Lucielli

    2012-07-01

    In this study, the antioxidant and antidepressant-like effects of α-(phenylselanyl) acetophenone (PSAP), an organoselenium compound, were investigated. To assess the in vitro antioxidant properties, PSAP was evaluated in four test systems (DPPH, ABTS, FRAP and inhibition of lipid peroxidation). PSAP (100-500 μM) showed potent antioxidant activity and protected against lipid peroxidation. Additionally, we investigated whether PSAP, when administered in mice (100, 200 and 400mg/kg, per oral, p.o.), could cause acute toxicity. Our results demonstrated that PSAP did not cause the death of any animal, significantly reduce body weight or cause any oxidative tissue stress following treatment. This study also evaluated the effect of PSAP (0.1-10 mg/kg, p.o) on mice in a forced swim test (FST) and tail suspension test (TST), assays that are predictive of depressant activity and motor activity in the open-field. PSAP (5-10 mg/kg) significantly reduced immobility time in the FST and TST without affecting motor activity. In addition, the antidepressant-like effect caused by PSAP (5m/kg, p.o) in mice during the TST was dependent on an interaction with the serotonergic system (5-HT(1A) receptors), but not with the noradrenergic, dopaminergic or adenosinergic system. Together, these results suggest that PSAP possesses antioxidant and antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders.

  4. Serotonin 5-HT2A receptor gene variants influence antidepressant response to repeated total sleep deprivation in bipolar depression.

    PubMed

    Benedetti, Francesco; Barbini, Barbara; Bernasconi, Alessandro; Fulgosi, Mara Cigala; Colombo, Cristina; Dallaspezia, Sara; Gavinelli, Chiara; Marino, Elena; Pirovano, Adele; Radaelli, Daniele; Smeraldi, Enrico

    2008-12-12

    5-HT2A receptor density in prefrontal cortex was associated with depression and suicide. 5-HT2A receptor gene polymorphism rs6313 was associated with 5-HT2A receptor binding potential, with the ability of individuals to use environmental support in order to prevent depression, and with sleep improvement after antidepressant treatment with mirtazapine. Studies on response to antidepressant drugs gave inconsistent results. Here we studied the effect of rs6313 on response to repeated total sleep deprivation (TSD) in 80 bipolar depressed inpatients treated with three consecutive TSD cycles (each one made of 36 h awake followed by a night of undisturbed sleep). All genotype groups showed comparable acute effects of the first TSD, but patients homozygotes for the T variant had better perceived and observed benefits from treatment than carriers of the C allele. These effects became significant after the first recovery night and during the following days, leading to a 36% higher final response rate (Hamilton depression rating<8). The higher density of postsynaptic excitatory 5-HT2A receptors in T/T homozygotes could have led to higher behavioural effects of increased 5-HT neurotransmission due to repeated TSD. Other possible mechanisms involve allostatic/homeostatic adaptation to sleep loss, and a different effect of the allele variants on epigenetic influences. Results confirm the interest for individual gene variants of the serotonin pathway in shaping clinical characteristics of depression and antidepressant response.

  5. Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test.

    PubMed

    Lim, Dong Wook; Lee, Mi-Sook; Her, Song; Cho, Suengmok; Lee, Chang-Ho; Kim, In-Ho; Han, Daeseok

    2016-02-27

    Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o.) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR). Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression.

  6. Hippocampal Neurogenesis and Antidepressive Therapy: Shocking Relations

    PubMed Central

    Rotheneichner, Peter; Lange, Simona; O'Sullivan, Anna; Marschallinger, Julia; Zaunmair, Pia; Geretsegger, Christian; Aigner, Ludwig

    2014-01-01

    Speculations on the involvement of hippocampal neurogenesis, a form of neuronal plasticity, in the aetiology of depression and the mode of action of antidepressive therapies, started to arise more than a decade ago. But still, conclusive evidence that adult neurogenesis contributes to antidepressive effects of pharmacological and physical therapies has not been generated yet. This review revisits recent findings on the close relation between the mode(s) of action of electroconvulsive therapy (ECT), a powerful intervention used as second-line treatment of major depression disorders, and the neurogenic response to ECT. Following application of electroconvulsive shocks, intricate interactions between neurogenesis, angiogenesis, and microglia activation, the hypothalamic-pituitary-adrenal axis and the secretion of neurotrophic factors have been documented. Furthermore, considering the fact that neurogenesis strongly diminishes along aging, we investigated the response to electroconvulsive shocks in young as well as in aged cohorts of mice. PMID:24967107

  7. 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

  8. The neurobiology of depression and antidepressant action.

    PubMed

    Willner, Paul; Scheel-Krüger, Jørgen; Belzung, Catherine

    2013-12-01

    We present a comprehensive overview of the neurobiology of unipolar major depression and antidepressant drug action, integrating data from affective neuroscience, neuro- and psychopharmacology, neuroendocrinology, neuroanatomy, and molecular biology. We suggest that the problem of depression comprises three sub-problems: first episodes in people with low vulnerability ('simple' depressions), which are strongly stress-dependent; an increase in vulnerability and autonomy from stress that develops over episodes of depression (kindling); and factors that confer vulnerability to a first episode (a depressive diathesis). We describe key processes in the onset of a 'simple' depression and show that kindling and depressive diatheses reproduce many of the neurobiological features of depression. We also review the neurobiological mechanisms of antidepressant drug action, and show that resistance to antidepressant treatment is associated with genetic and other factors that are largely similar to those implicated in vulnerability to depression. We discuss the implications of these conclusions for the understanding and treatment of depression, and make some strategic recommendations for future research.

  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. Involvement of PI3K/Akt/GSK-3β and mTOR in the antidepressant-like effect of atorvastatin in mice.

    PubMed

    Ludka, Fabiana Kalyne; Constantino, Leandra Celso; Dal-Cim, Tharine; Binder, Luisa Bandeira; Zomkowski, Andréa; Rodrigues, Ana Lúcia S; Tasca, Carla Inês

    2016-11-01

    Atorvastatin is a cholesterol-lowering statin that has been shown to exert several pleiotropic effects in the nervous system as a neuroprotective and antidepressant-like agent. Antidepressant-like effect of atorvastatin in mice is mediated by glutamatergic and serotoninergic receptors, although the precise intracellular signaling pathways involved are unknown. PI3K/Akt/GSK-3β/mTOR signaling pathway has been associated to neurobiology of depression and seems to be modulated by some pharmacological antidepressant strategies. The present study investigated the participation of the PI3K/Akt/GSK-3β/mTOR signaling pathway in the antidepressant-like effect of an acute atorvastatin treatment in mice. Atorvastatin sub-effective (0.01 mg/kg) or effective (0.1 mg/kg) doses in the tail suspension test (TST) was administered orally alone or in combination with PI3K, GSK-3β or mTOR inhibitors. The administration of PI3K inhibitor, LY294002 (10 nmol/site, i.c.v) completely prevented the antidepressant-like effect of atorvastatin (0.1 mg/kg, p.o.). The participation of GSK-3β in the antidepressant-like effect of atorvastatin was demonstrated by co-administration of a sub-effective dose of atorvastatin (0.01 mg/kg, p.o.) with AR-A014418 (0.01 μg/site, i.c.v., a selective GSK-3β inhibitor) or with lithium chloride (10 mg/kg, p.o., a non-selective GSK-3β inhibitor). The mTOR inhibitor, rapamycin (0.2 nmol/site, i.c.v.) was also able to prevent atorvastatin (0.1 mg/kg, p.o.) antidepressant-like effect. These behavioral findings were supported by neurochemical observations, as atorvastatin treatment increased the immunocontent of the phosphorylated isoforms of Akt, GSK-3β and mTOR in the hippocampus of mice. Taken together, our results suggest an involvement of the PI3K/Akt/GSK-3β/mTOR signaling pathway in the antidepressant-like effect of atorvastatin in mice.

  11. Involvement of PI3K/Akt/GSK-3β and mTOR in the antidepressant-like effect of atorvastatin in mice.

    PubMed

    Ludka, Fabiana Kalyne; Constantino, Leandra Celso; Dal-Cim, Tharine; Binder, Luisa Bandeira; Zomkowski, Andréa; Rodrigues, Ana Lúcia S; Tasca, Carla Inês

    2016-11-01

    Atorvastatin is a cholesterol-lowering statin that has been shown to exert several pleiotropic effects in the nervous system as a neuroprotective and antidepressant-like agent. Antidepressant-like effect of atorvastatin in mice is mediated by glutamatergic and serotoninergic receptors, although the precise intracellular signaling pathways involved are unknown. PI3K/Akt/GSK-3β/mTOR signaling pathway has been associated to neurobiology of depression and seems to be modulated by some pharmacological antidepressant strategies. The present study investigated the participation of the PI3K/Akt/GSK-3β/mTOR signaling pathway in the antidepressant-like effect of an acute atorvastatin treatment in mice. Atorvastatin sub-effective (0.01 mg/kg) or effective (0.1 mg/kg) doses in the tail suspension test (TST) was administered orally alone or in combination with PI3K, GSK-3β or mTOR inhibitors. The administration of PI3K inhibitor, LY294002 (10 nmol/site, i.c.v) completely prevented the antidepressant-like effect of atorvastatin (0.1 mg/kg, p.o.). The participation of GSK-3β in the antidepressant-like effect of atorvastatin was demonstrated by co-administration of a sub-effective dose of atorvastatin (0.01 mg/kg, p.o.) with AR-A014418 (0.01 μg/site, i.c.v., a selective GSK-3β inhibitor) or with lithium chloride (10 mg/kg, p.o., a non-selective GSK-3β inhibitor). The mTOR inhibitor, rapamycin (0.2 nmol/site, i.c.v.) was also able to prevent atorvastatin (0.1 mg/kg, p.o.) antidepressant-like effect. These behavioral findings were supported by neurochemical observations, as atorvastatin treatment increased the immunocontent of the phosphorylated isoforms of Akt, GSK-3β and mTOR in the hippocampus of mice. Taken together, our results suggest an involvement of the PI3K/Akt/GSK-3β/mTOR signaling pathway in the antidepressant-like effect of atorvastatin in mice. PMID:27468164

  12. The influence of tobacco smoke and nicotine on antidepressant and memory-improving effects of venlafaxine.

    PubMed

    Nowakowska, Elzbieta; Kus, Krzysztof; Florek, Ewa; Czubak, Anna; Jodynis-Liebert, Jadwiga

    2006-04-01

    In experimental and clinical studies, central nicotinic systems have been shown to play an important role in cognitive function. Nicotinic acetylcholine receptors also mediate the reinforcing properties of nicotine (NIC) in tobacco products. A variety of studies have shown that acute treatment with NIC or nicotinic agonists can improve working memory function. Moreover, it is known that the monoaminergic system plays an important role in memory function. And there is evidence suggesting that prolonged use of NIC may exert antidepressant action via nicotinic receptors. The purpose of this study was to investigate the interactions between a novel antidepressant, venlafaxine (VEN), a blocker of noradrenaline and 5-hydroxytryptamine reuptake sites, and pure NIC in the context of antidepressant and memory function in tobacco smoke exposed and nonexposed rats. The animals were subjected to Porsolt's test for testing antidepressant activity and their memory function (spatial memory) was evaluated in the Morris Water Maze Test. In tobacco smoke non-exposed and exposed rats both single and chronic administration of VEN (20 mg/kg po) shortened immobility time. NIC (0.2 mg/kg sc) significantly reduced immobility time on the 1st, 7th and 14th test days in both non-exposed and exposed rats. Combined VEN+NIC treatment in tobacco smoke non-exposed rats reduced immobility too. This effect of the combination of drugs was significantly stronger as compared to the effects obtained after individual administration of VEN or NIC. In the group exposed to tobacco smoke, joint administration of VEN+ NIC induced a significant reduction of immobility as compared to the control and NIC groups. In the Morris Water Maze Test single and chronic administration of VEN, lower values of escape latencies and lower numbers of crossed quadrants were noted in both exposed and non-exposed rats, which indicates improved performance. After administering NIC we could observe improvement of spatial memory in

  13. Acute and chronic tianeptine treatments attenuate ethanol withdrawal syndrome in rats.

    PubMed

    Uzbay, Tayfun; Kayir, Hakan; Celik, Turgay; Yüksel, Nevzat

    2006-05-01

    Effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10 and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and last chronic tianeptine injections and saline were done 30 min before ethanol withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats) was also tested after acute tianeptine treatments. Acute but not chronic tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol-dependent rats. Both acute and chronic tianeptine treatment produced some significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors and audiogenic seizures during the ethanol withdrawal. Our results suggest that acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.

  14. Antidepressants versus placebo in major depression: an overview.

    PubMed

    Khan, Arif; Brown, Walter A

    2015-10-01

    Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or non-profit agencies. This narrowing of the drug-placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM-III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant-placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive. PMID:26407778

  15. Antidepressants versus placebo in major depression: an overview

    PubMed Central

    Khan, Arif; Brown, Walter A

    2015-01-01

    Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug-placebo differences, these robust differences have not held up in the trials of the past couple of decades, whether sponsored by pharmaceutical companies or non-profit agencies. This narrowing of the drug-placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM-III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant-placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive. PMID:26407778

  16. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  17. Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant?

    PubMed

    Pinder, Roger M

    2005-03-01

    Noradrenaline has long played a key role in the way the etiology of depression is conceptualized and in the mechanism of action of many current antidepressants. Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), selective noradrenaline reuptake inhibitors (NRIs), the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine, and many atypicals, like mianserin and bupropion, influence, at least in part, central noradrenergic function. Enhancement of noradrenergic function may be particularly helpful in patients with melancholia. However, while noradrenaline will continue to be a target for research into the etiology and treatment of depression, it is unlikely that antidepressants acting solely on noradrenaline will be pursued. PMID:18568121

  18. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.

    PubMed

    Jiang, Wen; Zhang, Yun; Xiao, Lan; Van Cleemput, Jamie; Ji, Shao-Ping; Bai, Guang; Zhang, Xia

    2005-11-01

    The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, G(i/o) proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.

  19. Antidepressant drugs and the emergence of suicidal tendencies.

    PubMed

    Teicher, M H; Glod, C A; Cole, J O

    1993-03-01

    Although antidepressant medications represent the cornerstone of treatment for patients with moderate to severe clinical depression, they also carry serious risks. There is evidence which suggests that antidepressants can, in rare instances, induce or exacerbate suicidal tendencies. Nine clinical mechanisms have been proposed through which this may occur. These are: (a) energizing depressed patients to act on pre-existing suicidal ideation; (b) paradoxically worsening depression; (c) inducing akathisia with associated self-destructive or aggressive impulses; (d) inducing panic attacks; (e) switching patients into manic or mixed states; (f) producing severe insomnia or interfering with sleep architecture; (g) inducing an organic obsessional state; (h) producing an organic personality disorder with borderline features; and (i) exacerbating or inducing electroencephalogram (EEG) or other neurological disturbances. Epidemiological and controlled studies also provide data on the association between antidepressant drugs and suicidal ideation, attempts and fatalities. These include studies which: (a) suggest that electroconvulsive therapy may be more effective than antidepressant drugs in reducing the frequency of suicide attempts; (b) indicate that antidepressants may differ in their capacity to reduce the frequency of suicide attempts; (c) find that more overdose attempts were made by patients receiving maprotiline than placebo; and (d) suggest that fluoxetine may be associated with a greater risk of inducing de novo suicidal ideation. Evidence suggests that antidepressants may vary by at least 15-fold in the number of fatal overdoses per million prescriptions. Estimated overdose proclivity rates were derived after adjusting the fatal toxicity data by the therapeutic index of the drug. These rates were very consistent between agents with the same pharmacological properties, and correlated well with known overdose risk rates for amitriptyline, mianserin and maprotiline

  20. Treatment Outcome in Older Patients with Childhood Acute Myeloid Leukemia

    PubMed Central

    Rubnitz, Jeffrey E.; Pounds, Stanley; Cao, Xueyuan; Jenkins, Laura; Dahl, Gary; Bowman, W. Paul; Taub, Jeffrey W; Pui, Ching-Hon; Ribeiro, Raul C.; Campana, Dario; Inaba, Hiroto

    2013-01-01

    Background Older age has historically been an adverse prognostic factor in pediatric acute myeloid leukemia (AML). The impact of age relative to that of other prognostic factors on the outcome of patients treated in recent trials is unknown. Methods Clinical outcome and causes of treatment failure of 351 patients enrolled on three consecutive protocols for childhood AML between 1991 and 2008 were analyzed according to age and protocol. Results The more recent protocol (AML02) produced improved outcomes for 10- to 21-year-old patients compared to 2 earlier studies (AML91 and 97), with 3-year rates of event-free survival (EFS), overall survival (OS) and cumulative incidence of refractory leukemia or relapse (CIR) for this group similar to those of 0- to 9-year old patients: EFS, 58.3% ± 5.4% vs. 66.6% ± 4.9%, P=.20; OS, 68.9% ± 5.1% vs. 75.1% ± 4.5%, P=.36; cumulative incidence of refractory leukemia or relapse, 21.9% ± 4.4%; vs. 25.3% ± 4.1%, P=.59. EFS and OS estimates for 10–15-year-old patients overlapped those for 16–21-year-old patients. However, the cumulative incidence of toxic death was significantly higher for 10- to 21-year-old patients compared to younger patients (13.2% ± 3.6 vs. 4.5% ± 2.0%, P=.028). Conclusion The survival rate for older children with AML has improved on our recent trial and is now similar to that of younger patients. However, deaths from toxicity remain a significant problem in the older age group. Future trials should focus on improving supportive care while striving to develop more effective antileukemic therapy. PMID:22674050

  1. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  2. Midostaurin: an emerging treatment for acute myeloid leukemia patients

    PubMed Central

    Gallogly, Molly Megan; Lazarus, Hillard M

    2016-01-01

    Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination-agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin’s ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are

  3. Azithromycin versus cefaclor in the treatment of acute bacterial pneumonia.

    PubMed

    Kinasewitz, G; Wood, R G

    1991-10-01

    In this randomised, double-blind study carried out in 28 centres, azithromycin (500 mg single dose on day 1, followed by 250 mg once-daily on days 2-5) was compared with cefaclor (500 mg t.i.d. for 10 days) in the treatment of acute bacterial pneumonia. A total of 119 patients entered the study, and of these 71 were evaluable and included in the efficacy analysis. The overall satisfactory clinical response was 97.3% for azithromycin patients and 100% for cefaclor patients. The clinical cure rates of azithromycin and cefaclor were 46.9% and 41.0%, respectively; improvement was seen in an additional 46.9% of azithromycin-treated patients and in 59.0% of the cefaclor group. The bacteriological eradication rates were 80.4% and 92.6%, respectively. These rates of clinical and bacteriological efficacy, were not statistically different. Both antibiotics were well tolerated during the study; only two patients (one on each study drug) discontinued medication due to adverse events. The overall incidence of side effects was 18.9% (10 of 53 patients) for azithromycin- and 12.1% (eight of 66 patients) for cefaclor-treated patients. Gastrointestinal disturbances were the most commonly reported side effects (nine of 10 azithromycin-treated patients and six of eight cefaclor-treated patients). In addition, two cefaclor patients reported headache. All azithromycin side effects were mild or moderate in severity, but there were two severe occurrences in the cefaclor group (1 nausea, 1 vomiting) the later leading to discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Drugs, genes and the blues: pharmacogenetics of the antidepressant response from mouse to man.

    PubMed

    O'Leary, Olivia F; O'Brien, Fionn E; O'Connor, Richard M; Cryan, John F

    2014-08-01

    While antidepressant drugs are beneficial to many patients, current treatments for depression remain sub-optimal. Up to half of patients with a major depressive episode fail to achieve remission with a first line antidepressant treatment. Identification of the molecular mechanisms that dictate whether a patient will successfully respond to a particular antidepressant treatment while tolerating its side-effects is not only a major challenge in biological psychiatry research but is also one that shows great promise. This review summarises data from both clinical and preclinical studies that point to a role of specific genes in the response and resistance to antidepressant therapeutics. Moreover, we discuss how such findings have increased our understanding of the mechanism of action of antidepressant drugs. Finally, we comment on how this information may potentially influence the future development of personalised medicine approaches for the treatment of depression.

  5. 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

  6. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-26

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy.

  7. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-01

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy. PMID:26817927

  8. Minimally Invasive Treatment of Acute Intrahepatic Fluid Collections With Acute Biliary Pancreatitis

    PubMed Central

    Ambrosi, Antonio; Fersini, Alberto; Tartaglia, Nicola; Valentino, Tiziano Pio

    2009-01-01

    Background: Peripancreatic fluid collection suggests the anatomical-clinical scenario of necrotizing acute pancreatitis. However, intrahepatic fluid collection is a rare occurrence with fewer than 30 cases being reported in the medical literature. We describe 2 cases of intrahepatic fluid collection in 2 patients with acute biliary pancreatitis and discuss the therapeutic possibilities. Case Reports: The first case report is that of a 68-year-old female with a diagnosis of acute biliary pancreatitis with several necrotizing fluid collections and a large infected intrahepatic collection in the left lobe. The patient was successfully treated by percutaneous US/CT guided drainage. The second case report is that of a 72-year-old female with a diagnosis of acute biliary pancreatitis with several peripancreatic fluid collections and a voluminous intrahepatic fluid collection in the left lobe that caused epigastric pain. This patient was also successfully treated with percutaneous US/CT guided drainage. Conclusion: Intrahepatic fluid collection in the course of acute biliary pancreatitis is a rare occurrence. The therapeutic approach is the same as that for pancreatic and peripancreatic fluid collections. In case of infection, the patient undergoes percutaneous US/CT guided drainage. This therapeutic procedure can be added to the therapeutic program for necrotizing acute biliary pancreatitis together with ERCP/ES and videolaparocholecystectomy (VLC). PMID:19660231

  9. Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine

    PubMed Central

    Kaur, Ginpreet; Invally, Mihir; Sanzagiri, Resham; Buttar, Harpal S.

    2015-01-01

    Background: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. Objective: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. Materials and Methods: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). Results: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of

  10. Maternal Depressive Symptoms in Pediatric Major Depressive Disorder: Relationship to Acute Treatment Outcome

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Hughes, Jennifer L.; Stewart, Sunita M.; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J.

    2008-01-01

    A study examined maternal depressive symptoms at the beginning and end of acute pediatric treatment of children with major depressive disorder (MDD). Results suggested a direct and possible reciprocal association between maternal and child depression severity.

  11. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  12. Successful treatment of acute systemic anaphylaxis in a western lowland gorilla (Gorilla gorilla gorilla).

    PubMed

    Hayman, David T S; King, Tony; Cameron, Kenneth

    2010-09-01

    This brief communication describes the successful treatment of acute systemic anaphylaxis in a wild-born but captive infant western lowland gorilla (Gorilla gorilla gorilla) in the Republic of Congo. The infant demonstrated signs of acute respiratory distress, lingual swelling, and reaction to intradermal tuberculin, given 55 hr earlier. Details of the treatment with steroids, anesthetic induction, and i.v. epinephrine are all reported, and potential antigens that may have initiated the anaphylactic shock are discussed.

  13. Impact of Antidepressant Drugs on Sexual Function and Satisfaction.

    PubMed

    Baldwin, David S; Manson, Chris; Nowak, Magda

    2015-11-01

    Pleasurable sexual activity is important in many human relationships and can provide a sense of physical, emotional and social well-being. Depressive symptoms and depressive illness are associated with impairments in sexual function and sexual dissatisfaction in untreated and treated patients. Most currently available antidepressant drugs are associated with development or worsening of sexual dysfunction in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts, but can persist over long periods, reducing self-esteem and affecting mood and relationships adversely. Sexual difficulties during antidepressant treatment typically have many possible causes but the incidence and nature of dysfunction varies between drugs. Many interventions can be considered when managing sexual dysfunction associated with antidepressants but no approach is 'ideal'. Because treatment-emergent sexual difficulties are less frequent with certain drugs, presumably related to differences in pharmacological properties, and since current interventions are suboptimal, a lower incidence of sexual dysfunction is a relevant tolerability target when developing novel antidepressants. PMID:26519341