Self-reported indications for antidepressant use in a population-based cohort of middle-aged and elderly.

PubMed

Aarts, Nikkie; Noordam, Raymond; Hofman, Albert; Tiemeier, Henning; Stricker, Bruno H; Visser, Loes E

2016-10-01

Background Population-based studies investigating indications for antidepressant prescribing mostly rely on diagnoses from general practitioners. However, diagnostic codes might be incomplete and drugs may be prescribed 'off-label' for indications not investigated in clinical trials. Objective We aimed to study indications for antidepressant use based on self-report. Also, we studied the presence of depressive symptoms associated with the self-reported indications. Setting Our study population of antidepressant users was selected based on interview data between 1997 and 2013 from the prospective population-based Rotterdam Study cohort (age >45 years). Method Antidepressant use, self-reported indication for use, and presence of depressive symptoms (Center for Epidemiological Studies Depression Scale) were based on interview. Self-reported indications were categorized by the researchers into officially approved, clinically-accepted and commonly mentioned off-label indications. Main outcome measures A score of 16 and higher on the Center for Epidemiological Studies Depression Scale was considered as indicator for clinically-relevant depressive symptoms. Results The majority of 914 antidepressant users reported 'depression' (52.4 %) as indication for treatment. Furthermore, anxiety, stress and sleep disorders were reported in selective serotonin reuptake inhibitor and other antidepressant users (ranging from 5.9 to 13.3 %). The indication 'pain' was commonly mentioned by tricyclic antidepressant users (19.0 %). Indications were statistically significantly associated with higher depressive symptom scores when compared to non-users (n = 10,979). Conclusions Depression was the main indication for antidepressant treatment. However, our findings suggest that antidepressants are also used for off-label indications, subthreshold disorders and complex situations, which were all associated with clinically-relevant depressive symptoms in the middle-aged and elderly

Non-monoaminergic targets for the development of antidepressants: focus on neuropeptides.

PubMed

Catena-Dell'Osso, Mario; Fagiolini, Andrea; Marazziti, Donatella; Baroni, Stefano; Bellantuono, Cesario

2013-01-01

In the last decades, no significant paradigm shifts in the psychopharmacology of major depressive disorder (MDD) have occurred. In fact, after the serendipitous discovery of the first antidepressant, the poor understanding of the pathophysiology of the illness has deeply limited the development of novel antidepressant agents. Although the discovery of the selective serotonin reuptake inhibitors and the dual-acting serotonin/norepinephrine reuptake inhibitors allowed to improve the treatment of MDD, there are still important unmet clinical needs, as the long latency of antidepressant action, the presence of relevant side effects and the lack of efficacy. In fact, even though the available antidepressants have consistently improved the prognosis of the disorder, the pharmacological treatment of MDD is far from being satisfactory and the disorder remains one of the major causes of morbidity and disability worldwide. Recently, besides the classical research involving the monoamines, other non-monoaminergic molecular mechanisms have been explored in search of new antidepressants. Amongst them, the investigation of the central neuropeptides, including substance P, corticotropin-releasing factor, neuropeptide Y, vasopressin and oxytocin, galanin and melanin-concentrating hormone, is increasingly attracting the attention of researchers worldwide. A number of novel compounds acting on neuropeptide receptors have been developed and tested in both animals and humans with different results. In this review, we provided a synthetic overview of the main neuropeptides, going through biochemical and molecular aspects up to preclinical and clinical evidence which link these molecules to the presence of MDD.

Depression, antidepressants, and bone mineral density in a population-based cohort.

PubMed

Mezuk, Briana; Eaton, William W; Golden, Sherita Hill; Wand, Gary; Lee, Hochang Benjamin

2008-12-01

It is uncertain whether depression and antidepressant use are associated with decreased bone mineral density (BMD) and whether these relationships differ for men and women. The study used a case-cohort design within the Baltimore Epidemiologic Catchment Area Study, a population-based sample of adults that recently completed its 23-year follow-up. Depression was measured at four time points during the follow-up period by the Diagnostic Interview Schedule. Lower spine BMD was measured at the fourth wave by dual-energy x-ray absorptiometry. The association of BMD with lifetime history of depression and antidepressant medication use was studied using linear regression with bootstrap standard errors. A history of depression was associated with lower spine BMD after controlling for age, sex, race, calcium intake, alcohol use, smoking status, level of physical activity, percent body fat, and antidepressant medication use (-0.140 g/cm(2); p <.002). After controlling for depression, antidepressant medication use was associated with decreased BMD in women but not in men (-0.218 g/cm(2); p <.016). A history of depression predicted decreased lumbar spine BMD in men and women, and antidepressant use predicted decreased BMD in women even after controlling for depression. The magnitude of the effect of depression on BMD was approximately equivalent to 1 standard deviation in BMD and was therefore clinically significant. Providers should be aware of the physiologic consequences of depression as well as the possible risks to bone strength associated with antidepressant use in older patients.

Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness.

PubMed

Macedo, Danielle; Filho, Adriano José Maia Chaves; Soares de Sousa, Caren Nádia; Quevedo, João; Barichello, Tatiana; Júnior, Hélio Vitoriano Nobre; Freitas de Lucena, David

2017-01-15

The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, the focus of this narrative review is to compile the available studies regarding the influences of gut microbiota in behavior and depression and to show the antimicrobial effect of antidepressant drugs. A discussion regarding the possible contribution of the antimicrobial effect of antidepressant drugs to its effectiveness/resistance is included. The search included relevant articles from PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge. MDD is associated with changes in gut permeability and microbiota composition. In this respect, antidepressant drugs present antimicrobial effects that could also be related to the effectiveness of these drugs for MDD treatment. Conversely, some antimicrobials present antidepressant effects. Both antidepressants and antimicrobials present neuroprotective/antidepressant and antimicrobial effects. Further studies are needed to evaluate the participation of antimicrobial mechanisms of antidepressants in MDD treatment as well as to determine the contribution of this effect to antidepressant resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

Sexual dysfunction, depression, and the impact of antidepressants.

PubMed

Kennedy, Sidney H; Rizvi, Sakina

2009-04-01

Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.

Neurogenesis as a new target for the development of antidepressant drugs.

PubMed

Pascual-Brazo, Jesus; Baekelandt, Veerle; Encinas, Juan Manuel

2014-01-01

Thirteen years have passed since the neurogenic hypothesis of depression was postulated. One of its aspects, that decreased neurogenesis could be causative of the onset of depression has been difficult to prove. Another aspect, the prediction that increasing neurogenesis would not only be supportive but also required to produce clinical results by antidepressants has gathered experimental validation. Thus a question arises: should new antidepressant strategies based solely on increasing neurogenesis be pursued? At the risk of disappointing the audience, we will not provide a straight answer to this question in this review, but we do hope to enlighten the reader regarding what is known about adult hippocampal neurogenesis, the indications and evidence of its involvement in the onset and treatment of depression, and the advances that have been made in the field in recent years. As we will recount here, the main body of support in favor of the neurogenic hypothesis of depression is based more on intimation than actual proof. However the rare examples that provide support are sufficiently robust to justify investment of resources and effort to clarify the issue, even if the involvement of neurogenesis, both in the etiology and the treatment of depression, is only partial and comprises only subtle components of this complex mental disorder.

Learned helplessness activates hippocampal microglia in rats: A potential target for the antidepressant imipramine.

PubMed

Iwata, Masaaki; Ishida, Hisahito; Kaneko, Koichi; Shirayama, Yukihiko

An accumulating body of evidence has demonstrated that inflammation is associated with the pathology of depression. We recently found that psychological stress induces inflammation in the hippocampus of the rat brain through the inflammasome, a component of the innate immune system. Microglia, the resident macrophages in the brain, play a central role in the innate immune system and express inflammasomes; thus, we hypothesized that hippocampal microglia would be key mediators in the development of depression via stress-induced inflammation. To test this hypothesis and to determine how antidepressants modulate microglial function, we used immunohistochemistry to examine the morphological changes that occur in the hippocampal microglia of rats exposed to the learned helplessness (LH) paradigm. We noted significantly increased numbers of activated microglia in the granule cell layer, hilus, CA1, and CA3 regions of the hippocampi of LH rats. Conversely, administering imipramine to LH rats for 7days produced a significant decrease in the number of activated microglia in the hilus, but not in the other examined regions. Nonetheless, there were no significant differences in the combined number of activated and non-activated microglia either in LH or LH+imipramine rats relative to control rats. In addition, treating the naïve rats with imipramine or fluvoxamine produced no discernible microglial changes. These data suggest that stress activates hippocampal microglia, while certain antidepressants decrease the number of activated microglia in the hilus, but not in other hippocampal regions. Therefore, the hilus represents a candidate target region for the antidepressant imipramine. Copyright © 2016 Elsevier Inc. All rights reserved.

Age Assessment in Children: A Novel Cameriere's Stratagem.

PubMed

Attiguppe, Prabhakar Ramasetty; Yavagal, Chandrashekar; Maganti, Rekhamani; Mythri, P

2016-01-01

Age is one of the essential factors in establishing the identity of a person, especially in children. Age estimation plays an important part in treatment planning, forensic dentistry, legal issues, and paleodemographic research. The present study was an attempt to estimate the chronological age in children of Davangere population by using Cameriere's India specific formula. This was a retrospective observational study to estimate the chronological age in children of Davangere population. A total of 150 panoramic radiographs of patients aged between 6 and 15 years, including both sexes, were selected. Age was calculated by measuring open apices of seven right or left mandibular teeth using Adobe Photoshop software. Statistical analysis was performed to derive a regression equation for estimation of age, which showed that, of the variables X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , s, N 0 , the variables N 0 and X 4 were statistically noteworthy. Hence, these two variables were used to derive the linear regression formula: Age = 10.522 + 0.712(N 0 ) - 5.040(X 4 ). The model was found to be statistically significant, F(2, 147) = 207.96, p < 0.001, and accounted for approximately 74% of the variance of age (R 2 = 0.739, adjusted R 2 = 0.735). Cameriere's method can be used for age assessment in children for forensic as well as legal contexts and based on these variables a reliable age estimation equation could be proposed specifically for Davangere population. Attiguppe PR, Yavagal C, Maganti R, Mythri P. Age Assessment in Children: A Novel Cameriere's Stratagem. Int J Clin Pediatr Dent 2016;9(4):330-334.

Anti-depressant medication use and C-reactive protein: results from two population-based studies.

PubMed

Hamer, Mark; Batty, G D; Marmot, Michael G; Singh-Manoux, Archana; Kivimäki, Mika

2011-01-01

The use of anti-depressant medication has been linked to cardiovascular disease (CVD). We examined the association between anti-depressant medication use and a marker of low grade systemic inflammation as a potential pathway linking anti-depressant use and CVD in two population based studies. Data were collected in a representative sample of 8131 community dwelling adults (aged 47.4±15.9 years, 46.7% male) from the Scottish Health Surveys (SHS). The use of anti-depressant medication was coded according to the British National Formulary and blood was drawn for the measurement of C-reactive protein (CRP). In a second study, we attempted to replicate our findings using longitudinal data from the Whitehall II study (n=4584, aged 55.5±5.9 years, mean follow-up 5.5 years). Antidepressants were used in 5.6% of the SHS sample, with selective serotonin reuptake inhibitors (SSRIs) being the most common. There was a higher risk of elevated CRP (>3 mg/L) in users of tricyclic antidepressant (TCA) medication (multivariate adjusted odds ratio (OR)=1.52, 95% CI, 1.07-2.15), but not in SSRI users (multivariate adjusted OR=1.07, 95% CI, 0.81-1.42). A longitudinal association between any antidepressant use and subsequent CRP was confirmed in the Whitehall cohort. In summary, the use of anti-depressants was associated with elevated levels of systemic inflammation independently from the symptoms of mental illness and cardiovascular co-morbidity. This might be a potential mechanism through which antidepressant medication increases CVD risk. Further data are required to explore the effects of dosage and duration of antidepressant treatment. Copyright © 2010 Elsevier Inc. All rights reserved.

Tricyclic Antidepressants and Tetracyclic Antidepressants

MedlinePlus

... dangerous reactions when combined with certain medications or herbal supplements. Serotonin syndrome. Rarely, an antidepressant can cause high ... antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Signs and symptoms of serotonin ...

The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

PubMed

Lin, Chen-Ju; Robert, Francis; Sukarieh, Rami; Michnick, Stephen; Pelletier, Jerry

2010-04-15

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. (c) 2010 AACR.

[Mechanism of action of antidepressants and therapeutic perspectives].

PubMed

Bourin, M; David, D J P; Jolliet, P; Gardier, A

2002-01-01

Depression is an incapacitating disease which needs appropriate treatment. This article reviews the pharmacology of antidepressant drugs and the future perspectives of treating mood disorders such as depression. The foremost theory for explaining the biological basis of depression has been the monoamine hypothesis. Depression is due to a deficiency in one or other biogenic monoamines (serotonin, 5-HT; noradrenaline, NA; dopamine, DA). Antidepressant drugs are therefore classified according to their ability to improve monoaminergic transmission. Since this first theory, other explanations based on abnormal function of monoamine receptors or associated with impaired signalling pathways have been suggested. Notable progress has been accomplished in the treatment of major depressive disorders with new compounds recently discovered (selective serotonin reuptake inhibitors: SSRI; serotonin noradrenaline reuptake inhibitors: SNRI). Behavioural, electrophysiological and microdialysis studies have shown that serotonin (5-HT) receptors, mainly 5-HT1A, 5-HT1B and 5-HT2C sub-types, exert a key role in modulating antidepressant activity. Indirect activation of neurotransmitter receptors by antidepressants may also lead, via increases in endogenous levels of serotonin in synapses in specific brain regions, to activation of various G proteins coupled to a receptor, signal of transduction, transcription factors and neurotrophic factors such as brain-derived neurotrophic factor (BDNF). Thus, depression may be considered as a transduction mechanism anomaly. This hypothesis needs to be clarified by molecular biology. Although antidepressants have improved the therapeutic potential compared to tricyclics (TCA) in terms of reduced side effects, a number of problems still occur with these drugs. Clinical effects are not always observed until after this time has elapsed (4-6 weeks) and a substantial proportion of depressed patients show only partial or no response to antidepressants

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

PubMed

Nguyen, Linda; Robson, Matthew J; Healy, Jason R; Scandinaro, Anna L; Matsumoto, Rae R

2014-01-01

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [(3)H](+)-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors.

Antidepressants during pregnancy and autism in offspring: population based cohort study

PubMed Central

Lee, Brian K; Dalman, Christina; Newschaffer, Craig; Lewis, Glyn; Magnusson, Cecilia

2017-01-01

Objectives To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring. Design Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison. Setting Stockholm County, Sweden. Participants 254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records. Main outcome measure Offspring diagnosis of autism spectrum disorder, with and without intellectual disability. Results Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers’ pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability. Conclusions The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the

Antidepressant-Induced Hyponatremia in Older Adults.

PubMed

Viramontes, Terry S; Truong, Havan; Linnebur, Sunny A

2016-03-01

To describe the prevalence of hyponatremia in older adults related to antidepressive agents and identify potential alternative options in older adults with a low-baseline serum sodium concentration and/or when a patient has experienced hyponatremia as a result of taking an antidepressant. A PubMed search was conducted on November 10, 2015. Search terms included: antidepressive agents, antidepressive agents second-generation, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, hyponatremia, milnacipran, mirtazapine, paroxetine, reboxetine, syndrome of inappropriate antidiuretic hormone, sertraline, trazodone, venlafaxine, and vilazodone. Filters included English language. A search of product labeling was also conducted. Out of 363 results, 124 publications were identified and reviewed along with 11 additional references. Publications were chosen based on relevance to the review: case reports of patients 60 years of age or older or clinical investigations of the association between hyponatremia and antidepressants in older adults. Hyponatremia was counted as an adverse effect if an antidepressant was the likely cause of hyponatremia, and hyponatremia was resolved after withdrawal. Antidepressant-induced hyponatremia in older adults is fairly common. Selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and mirtazapine were implicated in the majority of the case reports and clinical studies evaluating older adults. Bupropion, trazodone, and tricyclic antidepressants were implicated less often in the same literature. Given its unique mechanism of action, bupropion may be the most appropriate antidepressant for older adults at risk for antidepressant-induced hyponatremia.

Nitric Oxide Synthase Inhibitors as Antidepressants

PubMed Central

Wegener, Gregers; Volke, Vallo

2010-01-01

Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO) signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression. PMID:27713253

Involvement of Sigma-1 Receptors in the Antidepressant-like Effects of Dextromethorphan

PubMed Central

Nguyen, Linda; Robson, Matthew J.; Healy, Jason R.; Scandinaro, Anna L.; Matsumoto, Rae R.

2014-01-01

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [3H](+)-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors. PMID:24587167

Effects of Antidepressants on Sleep.

PubMed

Wichniak, Adam; Wierzbicka, Aleksandra; Walęcka, Małgorzata; Jernajczyk, Wojciech

2017-08-09

The aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of antidepressant drugs but are also related to the dose, the time of drug administration, and the duration of the treatment. Complaints of disrupted sleep are very common in patients suffering from depression, and they are listed among diagnostic criteria for this disorder. Moreover, midnocturnal insomnia is the most frequent residual symptom of depression. Thus, all antidepressants should normalize sleep. However, at least in short-term treatment, many antidepressants with so-called activating effects (e.g. fluoxetine, venlafaxine) may disrupt sleep, while others with sedative properties (e.g., doxepin, mirtazapine, trazodone) rapidly improve sleep, but may cause problems in long-term treatment due to oversedation.For sleep-promoting action, the best effects can frequently be achieved with a very low dose, administered early enough before bedtime and importantly, always as a part of more complex interventions based on the cognitive-behavioral protocol to treat insomnia (CBT-I). For successful treatment of depression, it is necessary to understand the effects of antidepressants on sleep. Each physician should also be aware that some antidepressants may worsen or induce primary sleep disorders like restless legs syndrome, sleep bruxism, REM sleep behavior disorder, nightmares, and sleep apnea, which may result from an antidepressant-induced weight gain.

Age Assessment in Children: A Novel Cameriere’s Stratagem

PubMed Central

Attiguppe, Prabhakar Ramasetty; Yavagal, Chandrashekar; Mythri, P

2016-01-01

Aim Age is one of the essential factors in establishing the identity of a person, especially in children. Age estimation plays an important part in treatment planning, forensic dentistry, legal issues, and paleodemographic research. The present study was an attempt to estimate the chronological age in children of Davangere population by using Cameriere’s India specific formula. Materials and methods This was a retrospective observational study to estimate the chronological age in children of Davangere population. A total of 150 panoramic radiographs of patients aged between 6 and 15 years, including both sexes, were selected. Age was calculated by measuring open apices of seven right or left mandibular teeth using Adobe Photoshop software. Results Statistical analysis was performed to derive a regression equation for estimation of age, which showed that, of the variables X1, X2, X3, X4, X5, X6, X7, s, N0, the variables N0 and X4 were statistically noteworthy. Hence, these two variables were used to derive the linear regression formula: Age = 10.522 + 0.712(N0) - 5.040(X4). The model was found to be statistically significant, F(2, 147) = 207.96, p < 0.001, and accounted for approximately 74% of the variance of age (R2 = 0.739, adjusted R2 = 0.735). Conclusion Cameriere’s method can be used for age assessment in children for forensic as well as legal contexts and based on these variables a reliable age estimation equation could be proposed specifically for Davangere population. How to cite this article Attiguppe PR, Yavagal C, Maganti R, Mythri P. Age Assessment in Children: A Novel Cameriere’s Stratagem. Int J Clin Pediatr Dent 2016;9(4):330-334. PMID:28127165

Antidepressants during pregnancy and autism in offspring: population based cohort study.

PubMed

Rai, Dheeraj; Lee, Brian K; Dalman, Christina; Newschaffer, Craig; Lewis, Glyn; Magnusson, Cecilia

2017-07-19

Objectives  To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring. Design  Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison. Setting  Stockholm County, Sweden. Participants  254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records. Main outcome measure  Offspring diagnosis of autism spectrum disorder, with and without intellectual disability. Results  Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability. Conclusions  The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the

Antidepressant Prescribing by Pediatricians: A Mixed-Methods Analysis.

PubMed

Tulisiak, Anne K; Klein, Jillian A; Harris, Emily; Luft, Marissa J; Schroeder, Heidi K; Mossman, Sarah A; Varney, Sara T; Keeshin, Brooks R; Cotton, Sian; Strawn, Jeffrey R

2017-01-01

Among pediatricians, perceived knowledge of efficacy, tolerability, dosing, and side effects of antidepressants represent significant sources of variability in the use of these medications in youth with depressive and anxiety disorders. Importantly, the qualitative factors that relate to varying levels of comfort with antidepressants and willingness to prescribe are poorly understood. Using a mixed-methods approach, in-depth interviews were conducted with community-based and academic medical center-based pediatricians (N = 14). Interviews were audio recorded and iteratively coded; themes were then generated using inductive thematic analysis. The relationship between demographic factors, knowledge of antidepressants, dosing, and side effects, as well as prescribing likelihood scores for depressive disorders, anxiety disorders or co-morbid anxiety and depressive disorders, were evaluated using mixed models. Pediatricians reported antidepressants to be effective and well-tolerated. However, the likelihood of individual physicians initiating an antidepressant was significantly lower for anxiety disorders relative to depressive disorders with similar functional impairment. Pediatricians considered symptom severity/functional impairment, age and the availability of psychotherapy as they considered prescribing antidepressants to individual patients. Antidepressant choice was related to the physician׳s perceived knowledge and comfort with a particular antidepressant, financial factors, and the disorder-specific evidence base for that particular medication and consultation with mental health practitioners. Pediatricians noted similar efficacy and tolerability profiles for antidepressants in youth with depressive disorders and anxiety disorders, but tended to utilize "therapy first" approaches for anxiety disorders relative to depressive disorders. Parental and family factors that influenced prescribing of antidepressants by pediatricians included parental ambivalence

Prenatal antidepressant exposure and risk of spontaneous abortion - a population-based study.

PubMed

Kjaersgaard, Maiken Ina Siegismund; Parner, Erik Thorlund; Vestergaard, Mogens; Sørensen, Merete Juul; Olsen, Jørn; Christensen, Jakob; Bech, Bodil Hammer; Pedersen, Lars Henning

2013-01-01

To estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy. From the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who were diagnosed with depression from the Danish Psychiatric Central Registry. Adjusted relative risks (aRR) of spontaneous abortion were estimated according to exposure to antidepressants or maternal depression using binomial regression. Of the 1,005,319 pregnancies (547,300 women) identified, 114,721 (11.4%) ended in a spontaneous abortion. We identified 22,061 pregnancies exposed to antidepressants and 1,843 with a diagnosis of depression with no antidepressant use, of which 2,637 (12.0%) and 205 (11.1%) ended in a spontaneous abortion, respectively. Antidepressant exposure was associated with an aRR of 1.14 (95% confidence interval (CI) 1.10-1.18) for spontaneous abortion compared with no exposure to antidepressants. Among women with a diagnosis of depression, the aRR for spontaneous abortion after any antidepressant exposure was 1.00 (95% CI 0.80-1.24). No individual selective serotonin reuptake inhibitor (SSRI) was associated with spontaneous abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and duloxetine were associated with spontaneous abortions among women with depression but we had no information on potential differences in disease severity and only few pregnancies were exposed in the population. We identified a slightly increased risk of spontaneous abortion associated with the use of antidepressants during pregnancy. However, among women with a diagnosis of depression, antidepressants in general or individual SSRI in particular were not associated with

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study

PubMed Central

Man, Kenneth K C; Chan, Esther W; Ip, Patrick; Coghill, David; Simonoff, Emily; Chan, Phyllis K L; Lau, Wallis C Y; Schuemie, Martijn J; Sturkenboom, Miriam C J M

2017-01-01

Objective To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Design Population based cohort study. Setting Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. Participants 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Main outcome measure Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Results Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). Conclusions The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by

Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study

PubMed Central

Agerbo, Esben; Ingstrup, Katja G; Musliner, Katherine; Meltzer-Brody, Samantha; Bergink, Veerle; Munk-Olsen, Trine

2017-01-01

Objective To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders. Design Population based cohort study. Setting Danish national registers. Participants 905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×106 person years at risk. Exposures for observational studies Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy). Main outcome measure First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models. Results Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group. Conclusions In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero

Relationship between antidepressant prescription and breast cancer: a population based study in Taiwan.

PubMed

Chen, Vincent Chin-Hung; Liao, Yin-To; Yeh, Dah-Cherng; Tseng, Hsien-Chun; Stewart, Robert; Lee, Charles Tzu-Chi

2016-07-01

To investigate the association between antidepressant prescription and breast cancer. The National Health Research Institute in Taiwan provided a database of 1 000 000 random subjects for this study. We identified 14 737 new antidepressant female users who were more than 15 years old during 1999-2005 with at least 10 prescriptions and one year exposure to an antidepressant. These were matched 1:1 by age and residence to non-antidepressant users from the same database to compare the risk of breast cancer. In a model adjusted by age, residence, insurance amount, and depressive disorder, antidepressant prescription was not associated with breast cancer risk. This held true for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants. There was no evidence for an association between antidepressant prescription and the risk of breast cancer. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Molecular and Cellular Mechanisms of Rapid-Acting Antidepressants Ketamine and Scopolamine

PubMed Central

Wohleb, Eric S.; Gerhard, Danielle; Thomas, Alex; Duman, Ronald S.

2017-01-01

Major depressive disorder (MDD) is a prevalent neuropsychiatric disease that causes profound social and economic burdens. The impact of MDD is compounded by the limited therapeutic efficacy and delay of weeks to months of currently available medications. These issues highlight the need for more efficacious and faster-acting treatments to alleviate the burdens of MDD. Recent breakthroughs demonstrate that certain drugs, including ketamine and scopolamine, produce rapid and long-lasting antidepressant effects in MDD patients. Moreover, preclinical work has shown that the antidepressant actions of ketamine and scopolamine in rodent models are caused by an increase of extracellular glutamate, elevated BDNF, activation of the mammalian target of rapamycin complex 1 (mTORC1) cascade, and increased number and function of spine synapses in the prefrontal cortex (PFC). Here we review studies showing that both ketamine and scopolamine elicit rapid antidepressant effects through converging molecular and cellular mechanisms in the PFC. In addition, we discuss evidence that selective antagonists of NMDA and muscarinic acetylcholine (mACh) receptor subtypes (i.e., NR2B and M1-AChR) in the PFC produce comparable antidepressant responses. Furthermore, we discuss evidence that ketamine and scopolamine antagonize inhibitory interneurons in the PFC leading to disinhibition of pyramidal neurons and increased extracellular glutamate that promotes the rapid antidepressant responses to these agents. Collectively, these studies indicate that specific NMDA and mACh receptor subtypes on GABAergic interneurons are promising targets for novel rapid-acting antidepressant therapies. PMID:26955968

Potentiation of omega-3 fatty acid antidepressant-like effects with low non-antidepressant doses of fluoxetine and mirtazapine.

PubMed

Laino, Carlos Horacio; Fonseca, Cristina; Sterin-Speziale, Norma; Slobodianik, Nora; Reinés, Analía

2010-12-01

Despite the advances in psychopharmacology, the treatment of depressive disorders is still not satisfactory. Side effects and resistance to antidepressant drugs are the greatest complications during treatment. Based on recent evidence, omega-3 fatty acids may influence vulnerability and outcome in depressive disorders. The aim of this study was to further characterize the omega-3 antidepressant-like effect in rats in terms of its behavioral features in the depression model forced swimming test either alone or in combination with antidepressants fluoxetine or mirtazapine. Ultimately, we prompted to determine the lowest dose at which omega-3 fatty acids and antidepressant drugs may still represent a pharmacological advantage when employed in combined treatments. Chronic diet supplementation with omega-3 fatty acids produced concentration-dependent antidepressant-like effects in the forced swimming test displaying a behavioral profile similar to fluoxetine but different from mirtazapine. Fluoxetine or mirtazapine at antidepressant doses (10 and 20 mg/kg/day, respectively) rendered additive effects in combination with omega-3 fatty acid supplementation (720 mg/kg/day). Beneficial effects of combined treatment were also observed at sub-effective doses (1 mg/kg/day) of fluoxetine or mirtazapine, since in combination with omega-3 fatty acids (720 mg/kg/day), antidepressants potentiated omega-3 antidepressant-like effects. The antidepressant-like effects occurred in the absence of changes in brain phospholipid classes. The therapeutic approach of combining omega-3 fatty acids with low ineffective doses of antidepressants might represent benefits in the treatment of depression, especially in patients with depression resistant to conventional treatments and even may contribute to patient compliance by decreasing the magnitude of some antidepressant dose-dependent side effects. Copyright © 2010 Elsevier B.V. All rights reserved.

ANTIDEPRESSANT ADHERENCE ACROSS DIVERSE POPULATIONS AND HEALTHCARE SETTINGS.

PubMed

Rossom, Rebecca C; Shortreed, Susan; Coleman, Karen J; Beck, Arne; Waitzfelder, Beth E; Stewart, Christine; Ahmedani, Brian K; Zeber, John E; Simon, Greg E

2016-08-01

Early adherence is key to successful depression treatment, but nearly 60% of patients discontinue antidepressants within 3 months. Our study aimed to determine factors associated with poor early adherence to antidepressants in a large diverse sample of patients. Six Mental Health Research Network healthcare systems contributed data for adults with depression and a new antidepressant start, defined by a washout period of at least 270 days, between January 1, 2010 and December 31, 2012. Pharmacy fill and self-reported race/ethnicity data were obtained from the electronic medical record. Patients had early adherence if they had a second antidepressant fill within 180 days of the first. We used logistic regression to investigate the relationship between early adherence and patient characteristics. A total of 177,469 adult patients had 184,967 new episodes of depression with a filled antidepressant prescription. Patients refilled their antidepressants within 180 days in 71% of episodes. Race/ethnicity was a strong predictor of early adherence, with patients from racial/ethnic minorities other than Native Americans/Alaskan Natives less likely (adjusted odd ratios 0.50-0.59) to refill their antidepressants than non-Hispanic whites. Age, neighborhood education, comorbidity burden, provider type and engagement in psychotherapy were also associated with adherence. Other apparent predictors of early adherence, including neighborhood income, gender, and prior mental health hospitalizations, were no longer significant in the fully adjusted model. Race/ethnicity was a robust predictor of early antidepressant adherence, with minority groups other than Native Americans/Alaskan Natives less likely to be adherent. Further research is needed to determine whether early nonadherence in specific minority populations is intentional, due to side effects or patient preference, or unintentional and appropriate for targeted interventions to improve adherence. © 2016 Wiley Periodicals, Inc.

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study.

PubMed

Man, Kenneth K C; Chan, Esther W; Ip, Patrick; Coghill, David; Simonoff, Emily; Chan, Phyllis K L; Lau, Wallis C Y; Schuemie, Martijn J; Sturkenboom, Miriam C J M; Wong, Ian C K

2017-05-31

Objective  To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Design  Population based cohort study. Setting  Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. Participants  190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Main outcome measure  Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Results  Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). Conclusions  The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained

Antidepressants and the risk of suicidal behaviors.

PubMed

Jick, Hershel; Kaye, James A; Jick, Susan S

2004-07-21

The relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has received considerable public attention recently. The use of such drugs among teenagers has been of particular concern. To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin. Matched case-control study of patients treated in UK general practices using the UK General Practice Research Database for 1993-1999. The base population included 159,810 users of the 4 antidepressant drugs. Participants could have used only 1 of these antidepressants and had to have received at least 1 prescription for the study antidepressant within 90 days before their index date (the date of suicidal behavior or ideation for cases and the same date for matched controls). Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior. After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin. The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date. Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and

Involvement of PI3K/Akt Signaling Pathway and Its Downstream Intracellular Targets in the Antidepressant-Like Effect of Creatine.

PubMed

Cunha, Mauricio P; Budni, Josiane; Ludka, Fabiana K; Pazini, Francis L; Rosa, Julia Macedo; Oliveira, Ágatha; Lopes, Mark W; Tasca, Carla I; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

2016-07-01

Creatine has been proposed to exert beneficial effects in the management of depression, but the cell signaling pathways implicated in its antidepressant effects are not well established. This study investigated the involvement of PI3K/Akt signaling pathway and its downstream intracellular targets in the antidepressant-like effect of creatine. The acute treatment of mice with creatine (1 mg/kg, po) increased the Akt and P70S6K phosphorylation, and HO-1, GPx and PSD95 immunocontents. The pretreatment of mice with LY294002 (10 nmol/mouse, icv, PI3K inhibitor), wortmannin (0.1 μg/mouse, icv, PI3K inhibitor), ZnPP (10 μg/mouse, icv, HO-1 inhibitor), or rapamycin (0.2 nmol/mouse, icv, mTOR inhibitor) prevented the antidepressant-like effect of creatine (1 mg/kg, po) in the TST. In addition, the administration of subeffective dose of either the selective GSK3 inhibitor AR-A014418 (0.01 μg/mouse, icv), the nonselective GSK3 inhibitor lithium chloride (10 mg/kg, po), or the HO-1 inductor CoPP (0.01 μg/mouse, icv), in combination with a subeffective dose of creatine (0.01 mg/kg, po) reduced the immobility time in the TST as compared with either drug alone. No treatment caused significant changes in the locomotor activity of mice. These results indicate that the antidepressant-like effect of creatine in the TST depends on the activation of Akt, Nrf2/HO-1, GPx, and mTOR, and GSK3 inhibition.

Atypical Antidepressants

MedlinePlus

... dangerous reactions when combined with certain medications or herbal supplements. Serotonin syndrome. Rarely, an antidepressant can cause high ... antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Symptoms of serotonin syndrome include ...

Antidepressant prescribing and changes in antidepressant poisoning mortality and suicide in England, 1993-2004.

PubMed

Morgan, Oliver; Griffiths, Clare; Majeed, Azeem

2008-03-01

In England, the impact of increased use of antidepressant medications is unclear. We examine associations between antidepressant use, suicide and antidepressant poisoning mortality, adjusted for important covariates. Data on suicide and antidepressant poisoning mortality were provided by the Office for National Statistics. Prescription data were provided by the Department of Health. Age- and sex-specific prescribing rates were estimated from The Health Improvement Network primary care data. We measured the association between prescribing, suicide and poisoning mortality after adjusting for age, sex, calendar year, prescribing rates and use of newer antidepressants drugs. The prevalence of antidepressant treatment increased during the 1990s for all age and sex groups. Treatment prevalence remained constant from 2002 but declined among children and adolescents. Between 1993 and 2004, age-standardized rates for suicide decreased from 98.2 to 81.3 per million populations and for antidepressants from 9.2 to 7.4 per million populations. Before adjustment, increased antidepressant prescribing was associated with a decrease in suicide (r(s) = -0.90, P < 0.001) and antidepressant poisoning mortality rates (r(s) = -0.65, P = 0.023). This association disappeared after adjustment. In England, at a population level, there does not appear to be an association between antidepressant prescribing and antidepressant poisoning mortality or suicide.

Mammalian target of rapamycin (mTOR)/nitric oxide system possibly modulate antidepressant-like effect of 17α-ethinyl estradiol in ovariectomized mice.

PubMed

Saeedi Saravi, Seyed Soheil; Arefidoust, Alireza; Saeedi Saravi, Seyed Sobhan; Yaftian, Rahele; Bayati, Mahdi; Salehi, Milad; Dehpour, Ahmad Reza

2017-05-01

Due to a close association between depressive disorders and altered estrogen levels, this study was conducted to examine the hypothesis that antidepressant-like effect of ethinyl estradiol (EE 2) in ovariectomized mice is modulated by mammalian target of rapamycin (mTOR)/nitric oxide pathways. Female mice were undergone bilateral ovariectomy and different doses of EE 2 were intraperitoenally injected alone and combined with specific mTOR inhibitor, rapamycin, non-specific NOS inhibitor, L-NAME, nNOS inhibitor, 7-NI, NO precursor, l-arginine, and selective PDE5I, sildenafil. After locomotion assessment, immobility times were recorded in FST and TST. Moreover, hippocampal mTOR expression was assessed using western blot assay. The hippocampal concentrations of nitrite, a major metabolite of NO, were measured. Although EE 2 demonstrated a significant antidepressant-like activity in OVX mice, acute rapamycin exerted an unmarked decrease of the anti-immobility effect of EE 2 in FST and TST (P>0.05). In contrast, combination of minimal effective dose of EE 2 with sub- effective doses of either L-NAME (10mg/kg) or 7-NI (25mg/kg) resulted in a robust antidepressant-like effect in OVX mice. Administration of either L-NAME or 7-NI enhanced the decreased antidepressant activity of EE 2 induced by combination with rapamycin. Moreover, decrement of hippocampal mTOR expression in OVX mice was significantly enhanced by acute EE 2 . The increased hippocampal nitrite concentrations caused by ovariectomy were also reversed by EE 2 administration. The study demonstrated that acute treatment with lowest dose of EE 2 exerts significant antidepressant-like behavior in OVX mice, possibly, through mTOR activation. This effect seems to be also mediated by the suppression of nitric oxide pathway. Copyright © 2017. Published by Elsevier Masson SAS.

Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores

PubMed Central

Werner, Anna M.; Cuboni, Serena; Rudolf, Georg C.; Höfner, Georg; Wanner, Klaus T.; Sieber, Stephan A.; Schmidt, Ulrike; Holsboer, Florian; Rein, Theo; Hausch, Felix

2016-01-01

The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes. PMID:26863431

Risk Factors Associated With Antidepressant Exposure and History of Antidepressant-Induced Mania in Bipolar Disorder.

PubMed

Williams, Aislinn J; Lai, Zongshan; Knight, Seth; Kamali, Masoud; Assari, Shervin; McInnis, Melvin G

2018-05-15

Despite their widespread use in bipolar disorder, there is controversy surrounding the inclusion of antidepressant medications in the disorder's management. We sought to identify which demographic, socioeconomic, and clinical factors are associated with antidepressant exposure in bipolar disorder and which bipolar disorder patients are most likely to report a history of antidepressant-induced mania (AIM) when exposed to antidepressants. Our study included subjects with bipolar I disorder (n = 309), bipolar II disorder (n = 66), and bipolar disorder not otherwise specified (n = 27) and schizoaffective disorder, bipolar type (n = 14), from a longitudinal, community-based study. Subjects were evaluated using the Diagnostic Interview for Genetic Studies, modified for DSM-IV criteria. We applied multivariate logistical regression modeling to investigate which factors contribute to antidepressant exposure in bipolar disorder patients. We also used a logistic regression modeling approach to determine which clinical factors in bipolar disorder patients are associated with a history of AIM. Data were gathered from February 2006 through December 2010. Our results suggest that the risk factors most strongly associated with antidepressant exposure are female sex (OR = 2.73, P = .005), older age (OR = 1.03, P = .04), greater chronicity of illness (OR = 2.29, P = .04), and, to a lesser extent, white race (OR = 0.44, P = .051). Factors associated with reduced antidepressant exposure include history of affective psychosis (OR = 0.36, P = .01) and a greater number of previous manic episodes (OR = 0.98, P = .03). In subjects who reported a history of AIM, regression analysis revealed that the only statistically significant factor associated with AIM history was female sex (OR = 3.74, P = .02). These data suggest that there are certain identifiable factors associated with antidepressant exposure in bipolar disorder patients, and some of these, specifically female sex, are also

Depression, antidepressants and driving safety.

PubMed

Hill, Linda L; Lauzon, Vanessa L; Winbrock, Elise L; Li, Guohua; Chihuri, Stanford; Lee, Kelly C

2017-12-01

The purpose of this study was to review to review the reported associations of depression and antidepressants with motor vehicle crashes. A literature search for material published in the English language between January, 1995, and October, 2015, in bibliographic databases was combined with a search for other relevant material referenced in the retrieved articles. Retrieved articles were systematically reviewed for inclusion criteria: 19 epidemiological studies (17 case-control and 2 cohort studies) fulfilled the inclusion criteria by estimating the crash risk associated with depression and/or psychotropic medications in naturalistic settings. The estimates of the odds ratio (OR) of crash involvement associated with depression ranged from 1.78 to 3.99. All classes of antidepressants were reported to have side effects with the potential to affect driving safety. The majority of studies of antidepressant effects on driving reported an elevated crash risk, and ORs ranged from 1.19 to 2.03 for all crashes, and 3.19 for fatal crashes. In meta-analysis, depression was associated with approximately 2-fold increased crash risk (summary OR = 1.90; 95% CI, 1.06 to 3.39), and antidepressants were associated with approximately 40% increased crash risk (summary OR = 1.40; 95%CI, 1.18 to 1.66). Based on the findings of the studies reviewed, depression, antidepressants or the combination of depression and antidepressants may pose a potential hazard to driving safety. More research is needed to understand the individual contributions of depression and the medications used to treat depression.

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

Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study

PubMed Central

Booth, Helen P; Gulliford, Martin C

2018-01-01

Abstract Objective To evaluate the long term association between antidepressant prescribing and body weight. Design Population based cohort study. Setting General practices contributing to the UK Clinical Practice Research Datalink, 2004-14. Participants 136 762 men and 157 957 women with three or more records for body mass index (BMI). Main outcome measures The main outcomes were antidepressant prescribing, incidence of ≥5% increase in body weight, and transition to overweight or obesity. Adjusted rate ratios were estimated from a Poisson model adjusting for age, sex, depression recording, comorbidity, coprescribing of antiepileptics or antipsychotics, deprivation, smoking, and advice on diet. Results In the year of study entry, 17 803 (13.0%) men and 35 307 (22.4%) women with a mean age of 51.5 years (SD 16.6 years) were prescribed antidepressants. During 1 836 452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P<0.001). The risk of weight gain remained increased during at least six years of follow-up. In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of ≥5% weight gain was 27 (95% confidence interval 25 to 29). In people who were initially of normal weight, the adjusted rate ratio for transition to overweight or obesity was 1.29 (1.25 to 1.34); in people who were initially overweight, the adjusted rate ratio for transition to obesity was 1.29 (1.25 to 1.33). Associations may not be causal, and residual confounding might contribute to overestimation of associations. Conclusion Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight

The impact of sex as a biological variable in the search for novel antidepressants.

PubMed

Williams, Alexia V; Trainor, Brian C

2018-05-31

A roadblock to successful treatment for anxiety and depression is the high proportion of individuals that do not respond to existing treatments. Different underlying neurobiological mechanisms may drive similar symptoms, so a more personalized approach to treatment could be more successful. There is increasing evidence that sex is an important biological variable modulating efficacy of antidepressants and anxiolytics. We review evidence for sex-specific effects of traditional monoamine based antidepressants and newer pharmaceuticals targeting kappa opioid receptors (KOR), oxytocin receptors (OTR), and N-methyl-D-aspartate receptors (ketamine). In some cases, similar behavioral effects are observed in both sexes while in other cases strong sex-specific effects are observed. Most intriguing are cases such as ketamine which has similar behavioral effects in males and females, perhaps through sex-specific neurobiological mechanisms. These results show how essential it is to include both males and females in both clinical and preclinical evaluations of novel antidepressants and anxiolytics. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficient Purification and Release of Circulating Tumor Cells by Synergistic Effect of Biomarker and SiO2 @Gel-Microbead-Based Size Difference Amplification.

PubMed

Huang, Qinqin; Cai, Bo; Chen, Bolei; Rao, Lang; He, Zhaobo; He, Rongxiang; Guo, Feng; Zhao, Libo; Kondamareddy, Kiran Kumar; Liu, Wei; Guo, Shishang; Zhao, Xing-Zhong

2016-07-01

Microfluidics-based circulating tumor cell (CTC) isolation is achieved by using gelatin-coated silica microbeads conjugated to CTC-specific antibodies. Bead-binding selectively enlarges target cell size, providing efficient high-purity capture. CTCs captured can be further released non-invasively. This stratagem enables high-performance CTC isolation for subsequent studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

GABA interneurons mediate the rapid antidepressant-like effects of scopolamine

PubMed Central

Wohleb, Eric S.; Wu, Min; Gerhard, Danielle M.; Taylor, Seth R.; Picciotto, Marina R.; Alreja, Meenakshi; Duman, Ronald S.

2016-01-01

Major depressive disorder (MDD) is a recurring psychiatric illness that causes substantial health and socioeconomic burdens. Clinical reports have revealed that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, produces rapid antidepressant effects in individuals with MDD. Preclinical models suggest that these rapid antidepressant effects can be recapitulated with blockade of M1-type muscarinic acetylcholine receptors (M1-AChR); however, the cellular mechanisms underlying activity-dependent synaptic and behavioral responses to scopolamine have not been determined. Here, we demonstrate that the antidepressant-like effects of scopolamine are mediated by GABA interneurons in the medial prefrontal cortex (mPFC). Both GABAergic (GAD67+) interneurons and glutamatergic (CaMKII+) interneurons in the mPFC expressed M1-AChR. In mice, viral-mediated knockdown of M1-AChR specifically in GABAergic neurons, but not glutamatergic neurons, in the mPFC attenuated the antidepressant-like effects of scopolamine. Immunohistology and electrophysiology showed that somatostatin (SST) interneurons in the mPFC express M1-AChR at higher levels than parvalbumin interneurons. Moreover, knockdown of M1-AChR in SST interneurons in the mPFC demonstrated that M1-AChR expression in these neurons is required for the rapid antidepressant-like effects of scopolamine. These data indicate that SST interneurons in the mPFC are a promising pharmacological target for developing rapid-acting antidepressant therapies. PMID:27270172

GABA interneurons mediate the rapid antidepressant-like effects of scopolamine.

PubMed

Wohleb, Eric S; Wu, Min; Gerhard, Danielle M; Taylor, Seth R; Picciotto, Marina R; Alreja, Meenakshi; Duman, Ronald S

2016-07-01

Major depressive disorder (MDD) is a recurring psychiatric illness that causes substantial health and socioeconomic burdens. Clinical reports have revealed that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, produces rapid antidepressant effects in individuals with MDD. Preclinical models suggest that these rapid antidepressant effects can be recapitulated with blockade of M1-type muscarinic acetylcholine receptors (M1-AChR); however, the cellular mechanisms underlying activity-dependent synaptic and behavioral responses to scopolamine have not been determined. Here, we demonstrate that the antidepressant-like effects of scopolamine are mediated by GABA interneurons in the medial prefrontal cortex (mPFC). Both GABAergic (GAD67+) interneurons and glutamatergic (CaMKII+) interneurons in the mPFC expressed M1-AChR. In mice, viral-mediated knockdown of M1-AChR specifically in GABAergic neurons, but not glutamatergic neurons, in the mPFC attenuated the antidepressant-like effects of scopolamine. Immunohistology and electrophysiology showed that somatostatin (SST) interneurons in the mPFC express M1-AChR at higher levels than parvalbumin interneurons. Moreover, knockdown of M1-AChR in SST interneurons in the mPFC demonstrated that M1-AChR expression in these neurons is required for the rapid antidepressant-like effects of scopolamine. These data indicate that SST interneurons in the mPFC are a promising pharmacological target for developing rapid-acting antidepressant therapies.

Antidepressants and Alcohol

MedlinePlus

... the concern? Why is it bad to mix antidepressants and alcohol? Answers from Daniel K. Hall-Flavin, M.D. It's best to avoid combining antidepressants and alcohol. It may worsen your symptoms, and ...

Brain norepinephrine system as a target for antidepressant and mood stabilizing medications.

PubMed

Dremencov, Eliyahu; el Mansari, Mostafa; Blier, Pierre

2009-11-01

There are numerous lines of evidence pointing to norepinephrine being of crucial importance in pathophysiology of anxiety and mood disorders. First, norepinephrine projections innervate the limbic system, suggesting the involvement of norepinephrine in the regulation of emotions and cognition. Second, norepinephrine closely interacts with serotonin and dopamine systems, which also play very important roles in the regulation of mood. Third, it has been shown that various agents which increase norepinephrine availability, such as norepinephrine reuptake inhibitors, are also effective antidepressant drugs. And fourth, the depletion of norepinephrine causes a resurgence of depressive symptoms after successful treatment with antidepressant drugs. These observations suggest that the intensification of norepinephrine transmission can be beneficial in the treatment of affective disorders. However, various psychotropic medications have indirect effect on norepinephrine transmission. This review examines the effects of psychiatric medications on the norepinephrine system and proposes how they might be used to improve treatment outcome.

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

PubMed Central

Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

2016-01-01

Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

Alpha2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment.

PubMed

Yanpallewar, Sudhirkumar U; Fernandes, Kimberly; Marathe, Swananda V; Vadodaria, Krishna C; Jhaveri, Dhanisha; Rommelfanger, Karen; Ladiwala, Uma; Jha, Shanker; Muthig, Verena; Hein, Lutz; Bartlett, Perry; Weinshenker, David; Vaidya, Vidita A

2010-01-20

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. alpha(2)-Adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of alpha(2)-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that alpha(2)-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine beta-hydroxylase knock-out (Dbh(-/-)) mice lacking norepinephrine, supporting a role for alpha(2)-heteroceptors on progenitor cells, rather than alpha(2)-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitors in vitro express all the alpha(2)-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of alpha(2)-adrenoceptor stimulation on progenitors. Furthermore, coadministration of the alpha(2)-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short-duration (7 d) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that alpha(2)-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action

α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment

PubMed Central

Yanpallewar, Sudhirkumar U.; Fernandes, Kimberly; Marathe, Swananda V.; Vadodaria, Krishna C.; Jhaveri, Dhanisha; Rommelfanger, Karen; Ladiwala, Uma; Jha, Shanker; Muthig, Verena; Hein, Lutz; Bartlett, Perry; Weinshenker, David; Vaidya, Vidita A.

2010-01-01

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. α2-adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of α2-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that α2-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine β-hydroxylase knockout (Dbh −/−) mice lacking norepinephrine, supporting a role for α2-heteroceptors on progenitor cells, rather than α2-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitors in vitro express all the α2-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of α2-adrenoceptor stimulation on progenitors. Further, co-administration of the α2-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short duration (7 day) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that α2-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action, highlighting their importance as targets for

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…

Inductive reasoning in the context of discovery: Analogy as an experimental stratagem in the history and philosophy of science.

PubMed

Fisher, Amy A

2018-06-01

Building on Norton's "material theory of induction," this paper shows through careful historical analysis that analogy can act as a methodological principle or stratagem, providing experimentalists with a useful framework to assess data and devise novel experiments. Although this particular case study focuses on late eighteenth and early nineteenth-century experiments on the properties and composition of acids, the results of this investigation may be extended and applied to other research programs. A stage in-between what Steinle calls "exploratory experimentation" and robust theory, I argue that analogy encouraged research to substantiate why the likenesses should outweigh the differences (or vice versa) when evaluating results and designing experiments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Research on antidepressants in India

PubMed Central

Avasthi, Ajit; Grover, Sandeep; Aggarwal, Munish

2010-01-01

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

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

PubMed

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

2015-03-01

Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Conflict in Men’s Experiences With Antidepressants

PubMed Central

Gibson, Kerry; Cartwright, Claire; Read, John

2016-01-01

While men’s experiences of depression and help seeking are known to be shaped by gender, there is little research which examines their experience of using antidepressants to treat this. This study is based on in-depth, narrative-style interviews with 20 New Zealand men who had used antidepressants. The analysis identified a number of areas of conflict in the men’s accounts of using this medication. Conflict centered on the way taking antidepressants was seen as undermining personal control while also allowing users to take charge of their problems; facilitating general functioning while undermining sexual functioning; relieving emotional distress while undermining emotional vitality; and the tension participants felt between making autonomous judgments about the value of antidepressants and relying on the “expertise” of others. Participants negotiated these conflicts in a variety of ways. In some cases, antidepressants were positioned as being able to affirm aspects of traditional masculinity, while a smaller number of participants managed these conflicts by redefining aspects of their own masculinity in ways that contrasted with dominant constructions. This research is limited by the sample of older, more privileged men in the context of New Zealand culture which favors macho forms of masculinity. In similar contexts, mental health practitioners should be mindful of the conflicts that men might experience in relation to their antidepressant use. Facilitating men’s exploration of these issues may enable them to make better decisions about treatment options or to provide more effective support to those who have opted for antidepressant treatment. PMID:26993998

[The potential of group II metabotropic glutamate receptor antagonists as a novel antidepressant].

PubMed

Chaki, Shigeyuki

2012-08-01

Recently, abnormalities of glutamatergic transmission have been implicated in the pathophysiology of depression. Moreover, both ketamine, an NMDA receptor antagonist, and riluzole, a modulator of glutamatergic, transmission have been reported to be effective for the treatment of patients with treatment-refractory depression. Based on these findings, extensive studies to develop agents acting on glutamatergic transmission have been conducted. Glutamate receptors are divided into two main subtypes, ionotropic glutamate receptors and metabotropic glutamate (mGlu) receptors, both of which have subtypes. Of these, much attention has been paid to mGlu2/3 receptors. mGlu2/3 receptor antagonists such as MGS0039 and LY341495 have been reported to exert antidepressant effects in animal models of depression including the forced swim test, tail suspension test, learned helplessness paradigm, olfactory bulmectomy model and isolation rearing model, and to enhance serotonin release in the prefrontal cortex and dopamine release in the nucleus accumbens. Moreover, activation of AMPA receptor and mTOR signaling have been suggested to be involved in the antidepressant effects of mGlu2/3 receptor antagonists, as demonstrated in the actions of ketamine. Thus, mGlu2/3 receptor antagonists may share some neural networks with ketamine in exerting their antidepressant effects. In addition, the potential of other agents targeting glutamatergic transmission for novel antidepressants is being investigated.

Synthesis and evaluation of novel marine bromopyrrole alkaloid-based derivatives as potential antidepressant agents.

PubMed

Rane, Rajesh A; Napahde, Shital; Bangalore, Pavan Kumar; Sahu, Niteshkumar U; Shah, Nishant; Kulkarni, Yogesh A; Barve, Kalyani; Lokare, Leena; Karpoormath, Rajshekhar

2014-11-01

Herein, we report synthesis and screening of a series of twenty derivatives of bromopyrrole alkaloids with aroyl hydrazone feature for antidepressant activity by forced swim test (FST), tail suspension test (TST), and actophotometer method. The molecules were further evaluated for in vitro human MAO's inhibitory activities. The tested compounds exhibited moderate to good antidepressant activity compared with standard fluoxetine. Among these, most promising antidepressant derivatives 5b (%DID = 60.48), 5e (%DID = 59), and 5j (%DID = 74.86) reduced immobility duration of 50-70% at 30 mg/kg dose levels in FST. Further, derivative 5b, 5e, and 5j displayed good antidepressant activity with %DID value of 47.50, 46.62, and 52.49, respectively, in TST compared with standard fluoxetine (66.56% DID). Compound 5b showed high in vitro MAO-A potency and selectivity (Ki MAO-A (μM) = 2.4 ± 0.99, SI = 0.06) with promising pharmacological activity recognizing its potential as antidepressant lead candidate for further drug development. Study revealed that the presence of halogen atoms such as chlorine and fluorine at ortho- and/or para-position of phenyl ring and N-alkylation of pyrrole core is favored features for antidepressant activity. © 2014 John Wiley & Sons A/S.

Antidepressants and Youth: Healing or Harmful?

PubMed Central

Markowitz, Sara; Cuellar, Alison

2007-01-01

A series of drug innovations that began in 1987, including the introduction of several Selective Serotonin Reuptake Inhibitors (SSRIs) has led to a tremendous growth in the use of antidepressants in the United States. This growth, however, has been accompanied by a growing concern about the risks of prescribing antidepressants, particularly to children. Indeed, research linking the use of antidepressant drugs to an increased risk of suicidal behaviors in youth motivated the U.S. Food and Drug Administration to direct antidepressant drug manufacturers to include warning labels about the potential dangers. This paper examines the relationship between antidepressants and suicide among youth in the USA. Using state-level data on youth suicides and age-specific prescriptions for antidepressants, we find no relationships between suicides for adolescents ages 15 to 19 and prescriptions for Selective Serotonin Reuptake Inhibitors/Serotonin-Norepinephrine Reuptake Inhibitors or tricyclic and tetracyclic antidepressants. In contrast, we find that newer generation antidepressants are associated with lower numbers of suicides for this age group. For younger children, ages 10 to 14 we find no relationship with suicides for any type of antidepressant. PMID:17374550

Use of antidepressants in dentistry: A systematic review.

PubMed

Lino, P A; Martins, C C; Miranda, Gfpc; de Souza E Silva, M E; de Abreu, Mhng

2017-08-24

Previous research has suggested that antidepressants can be used in oral health care. The aim of this systematic review was to search for scientific evidence of the efficacy of the use of antidepressants in dentistry. The clinical question was as follows (PICO question): dentistry patients (Patients); antidepressants (Intervention); no use or placebo or other drug (Comparison); and efficacy in oral health problems (Outcome). An electronic search was conducted in seven databases, as well as a manual search without restriction regarding language and date of publication. Two independent reviewers selected studies based on eligibility criteria, extracted data and assessed methodological quality based on the PEDro scale. The PROSPERO record is number CRD42016037442. A total of 15 randomized controlled trials were associated with the use of antidepressants to control chronic or acute pain in dentistry, among other conditions such as bruxism and burning mouth syndrome. The most commonly used drug in clinical trials was amitriptyline (more than 50% of studies). Antidepressants may be effective in dentistry for acute and chronic pain, but there is a large amount of methodological heterogeneity among the evaluated studies. In summary, there is rationality for the indication of this class of medicine in dentistry in specific clinical situations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Higher anti-depressant dose and major adverse outcomes in moderate chronic kidney disease: a retrospective population-based study

PubMed Central

2014-01-01

Background Many older patients have chronic kidney disease (CKD), and a lower dose of anti-depressants paroxetine, mirtazapine and venlafaxine is recommended in patients with CKD to prevent drug accumulation from reduced elimination. Using information available in large population-based healthcare administrative databases, we conducted this study to determine if ignoring the recommendation and prescribing a higher versus lower dose of anti-depressants associates with a higher risk of adverse events. Methods We conducted a population-based cohort study to describe the 30-day risk of delirium in older adults who initiated a higher vs. lower dose of these three anti-depressants in routine care. We defined delirium using the best proxy available in our data sources - hospitalization with an urgent head computed tomography (CT) scan. We determined if CKD status modified the association between anti-depressant dose and outcome, and examined the secondary outcome of 30 day all-cause mortality. We used multivariable logistic regression analyses to estimate adjusted odds ratios (relative risk (RR)) and 95% confidence intervals. Results We identified adults (mean age 75) in Ontario who started a new study anti-depressant at a higher dose (n = 36,651; 31%) or lower dose (n = 81,160; 69%). Initiating a higher vs. lower dose was not associated with an increased risk of hospitalization with head CT (1.09% vs. 1.27% (adjusted RR 0.90; 95% CI, 0.80 to 1.02), but was associated with a lower risk of all-cause mortality (0.76% vs. 0.97% RR 0.82; 95% CI, 0.71 to 0.95). Neither of these relative risks were modified by the presence of CKD (p = 0.16, 0.68, respectively). Conclusions We did not observe an increase in two adverse outcomes when study anti-depressants were initiated at a higher dose in elderly patients with moderate CKD. Contrary to our hypothesis, the 30-day risk of mortality was lower when a higher versus lower dose of anti-depressant was initiated in these

Selective cortical VGLUT1 increase as a marker for antidepressant activity.

PubMed

Moutsimilli, Larissa; Farley, Severine; Dumas, Sylvie; El Mestikawy, Salah; Giros, Bruno; Tzavara, Eleni T

2005-11-01

The two recently characterized vesicular glutamate transporters (VGLUT) presynaptically mark and differentiate two distinct excitatory neuronal populations and thus define a cortical and a subcortical glutamatergic system (VGLUT1 and VGLUT2 positive, respectively). These two systems might be differentially implicated in brain neuropathology. Still, little is known on the modalities of VGLUT1 and VGLUT2 regulations in response to pharmacological or physiological stimuli. Given the importance of cortical neuronal activity in psychosis we investigated VGLUT1 mRNA and protein expression in response to chronic treatment with commonly prescribed psychotropic medications. We show that agents with antidepressant activity, namely the antidepressants fluoxetine and desipramine, the atypical antipsychotic clozapine, and the mood stabilizer lithium increased VGLUT1 mRNA expression in neurons of the cerebral cortex and the hippocampus and in concert enhanced VGLUT1 protein expression in their projection fields. In contrast the typical antipsychotic haloperidol, the cognitive enhancers memantine and tacrine, and the anxiolytic diazepam were without effect. We suggest that VGLUT1 could be a useful marker for antidepressant activity. Furthermore, adaptive changes in VGLUT1 positive neurons could constitute a common functional endpoint for structurally unrelated antidepressants, representing promising antidepressant targets in tracking specificity, mechanism, and onset at action.

Antidepressant use and functional limitations in U.S. older adults.

PubMed

An, Ruopeng; Lu, Lingyun

2016-01-01

The upsurge in prevalence and long-term use of antidepressants among older adults might have profound health implications beyond depressive symptom management. This study examined the relationship between antidepressant use and functional limitation onset in U.S. older adults. Study sample came from 2006 and 2008 waves of the Health and Retirement Study, in combination with data from 2005 and 2007 Prescription Drug Study. Self-reported antidepressant use was identified based on the therapeutic classification of Cerner Multum's Lexicon. Functional limitations were classified into those pertaining to physical mobility, large muscle function, activities of daily living, gross motor function, fine motor function, and instrumental activities of daily living. Cox proportional hazard models were performed to assess the effects of antidepressant use on future functional limitation onset by limitation category, antidepressant type, and length of use, adjusted by depression status and other individual characteristics. Antidepressant use for one year and longer was associated with an increase in the risk of functional limitation by 8% (95% confidence interval=4%-12%), whereas the relationship between antidepressant use less than a year and function limitation was statistically nonsignificant. Antidepressant use was associated with an increase in the risk of functional limitation by 8% (3%-13%) among currently nondepressed participants but not currently depressed participants. Long-term antidepressant use in older adults should be prudently evaluated and regularly monitored to reduce the risk of functional limitation. Future research is warranted to examine the health consequences of extended and/or off-label antidepressant use in absence of depressive symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Antidepressant monotherapy vs sequential pharmacotherapy and mindfulness-based cognitive therapy, or placebo, for relapse prophylaxis in recurrent depression.

PubMed

Segal, Zindel V; Bieling, Peter; Young, Trevor; MacQueen, Glenda; Cooke, Robert; Martin, Lawrence; Bloch, Richard; Levitan, Robert D

2010-12-01

Mindfulness-based cognitive therapy (MBCT) is a group-based psychosocial intervention designed to enhance self-management of prodromal symptoms associated with depressive relapse. To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy, the current standard of care. Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were randomized to receive maintenance antidepressant medication, MBCT, or placebo and were followed up for 18 months. Outpatient clinics at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and St Joseph's Healthcare, Hamilton, Ontario. One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes. Of these, 84 achieved remission (52.5%) and were assigned to 1 of the 3 study conditions. Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT, continued taking their therapeutic dose of antidepressant medication, or discontinued active medication and were switched to placebo. Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV. Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in randomized patients (P = .03). Among unstable remitters (1 or more Hamilton Rating Scale for Depression score >7 during remission), patients in both MBCT and maintenance treatment showed a 73% decrease in hazard compared with placebo (P = .03), whereas for stable remitters (all Hamilton Rating Scale for Depression scores ≤7 during remission) there were no group differences in survival. For depressed patients achieving stable or unstable clinical remission, MBCT offers protection against relapse

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

PubMed Central

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

2016-01-01

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

Pattern and predictors of sick leave among users of antidepressants: a Danish retrospective register-based cohort study.

PubMed

Gasse, Christiane; Petersen, Liselotte; Chollet, Julien; Saragoussi, Delphine

2013-12-01

Depression is associated with work absenteeism, reduced productivity, and significant personal and societal economic burden. We describe patterns and determinants of sick leave among working Danish antidepressant users. Persons starting antidepressant treatment (January 1, 2004 through December 31, 2005) were identified from a representative 25% sample of the Danish population by linking Danish national registries. Inclusion criteria were age 18-64 years, being in the workforce the week prior to the first antidepressant prescription (index prescription, IP), and no antidepressant prescription in the year prior to the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could be assessed. Cox regression analyses identified predictors of sick leave during the year following the IP, based on previous history of sick leave and clinical and socio-demographic baseline characteristics. In the cohort of 25,908 (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to 45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence peaked (35.5% of individuals) the week after the IP. Of persons with sick leave in the year before the IP, 62.7% were on sick leave the first week after the IP, vs 5.7% of those without previous sick leave. Predictors associated with increased risk of sick leave among those without previous sick leave were unemployment, female gender, age 25-54 years, couples with children, and vocational and higher intermediate education (including e.g. teachers and nurses). Reasons for sick leave, sick leaves of less than 14 days and the indications for antidepressant treatment were unknown. Sick leave was prevalent in persons starting new antidepressant use, often lasting >8 weeks. Previous sick leave was the strongest predictor of subsequent sick leave. © 2013 Elsevier B.V. All rights reserved.

Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

PubMed

Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

2014-01-01

The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

Adherence to Antidepressant Treatment Among Privately Insured Patients Diagnosed With Depression

PubMed Central

Akincigil, Ayse; Bowblis, John R.; Levin, Carrie; Walkup, James T.; Jan, Saira; Crystal, Stephen

2008-01-01

Background Antidepressants are effective in treatment of depression, but poor adherence to medication is a major obstacle to effective care. Objective We sought to describe patient and provider level factors associated with treatment adherence. Methods This was a retrospective, observational study using medical and pharmacy claims from a large health plan, for services provided between January 2003 and January 2005. We studied a total of 4312 subjects ages 18 or older who were continuously enrolled in the health plan with a new episode of major depression and who initiated antidepressant treatment. Treatment adherence was measured by using pharmacy refill records during the first 16 weeks (acute phase) and the 17–33 weeks after initiation of antidepressant therapy (continuation phase). Measures were based on Health Plan Employer Data and Information Set (HEDIS) quality measures for outpatient depression care. Results Fifty-one percent of patients were adherent through the acute phase; of those, 42% remained adherent in the continuation phase. Receipt of follow-up care from a psychiatrist and higher general pharmacy utilization (excluding psychotropics) were associated with better adherence in both phases. Younger age, comorbid alcohol or other substance abuse, comorbid cardiovascular/metabolic conditions, use of older generation antidepressants, and residence in lower-income neighborhoods were associated with lower acute-phase adherence. Continuation-phase adherence was lower for HMO participants than for others. Conclusion In an insured population, many patients fall short of adherence to guideline recommended therapy for depression. Information from existing administrative data can be used to predict patients at highest risk of nonadherence, such as those with substance abuse, and to target interventions. PMID:17496721

How fast are antidepressants?

PubMed

Gelenberg, A J; Chesen, C L

2000-10-01

For years, investigators have tried to determine the speed of onset of antidepressant drugs. Claims that particular drugs may produce a faster response in patients than other agents have been made, but such claims have never been confirmed. The authors reviewed reports from studies of the speed of onset of antidepressant therapies and other studies that revealed information on this topic. We compiled a list of factors that can affect the results of such studies and interpretations of study results. In addition, we reviewed literature concerned with methods of speeding up antidepressant responses. No antidepressant medication currently available has been shown conclusively to have a more rapid onset of action than any other. However, some methods of augmentation may have the potential to speed responses. Somatic therapies such as electroconvulsive therapy, phototherapy, and therapeutic sleep deprivation may be the fastest options available at this time. All available antidepressant medications are usually taken for several weeks before future responders will display a significant therapeutic benefit. If a patient does not show at least a 20% improvement within the first 2 to 4 weeks of treatment, the treatment regimen should be altered. For patients who do show early benefits from a medication trial, one can expect additional benefits to accrue over an 8- to 12-week period and to improve overall outcome compared with those slower to respond. Future trials need to address methodological confounds, but a truly "faster antidepressant" will probably require new neuroscience technology.

[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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties

PubMed Central

Guardiola-Lemaitre, B; De Bodinat, C; Delagrange, P; Millan, M J; Munoz, C; Mocaër, E

2014-01-01

Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors and as a neutral antagonist at 5-HT2C receptors. Accumulating evidence in a broad range of experimental procedures supports the notion that the psychotropic effects of agomelatine are due to the synergy between its melatonergic and 5-hydroxytryptaminergic effects. The recent demonstration of the existence of heteromeric complexes of MT1 and MT2 with 5-HT2C receptors at the cellular level may explain how these two properties of agomelatine translate into a synergistic action that, for example, leads to increases in hippocampal proliferation, maturation and survival through modulation of multiple cellular pathways (increase in trophic factors, synaptic remodelling, glutamate signalling) and key targets (early genes, kinases). The present review focuses on the pharmacological properties of this novel antidepressant. Its mechanism of action, strikingly different from that of conventional classes of antidepressants, opens perspectives towards a better understanding of the physiopathological bases underlying depression. PMID:24724693

Are studies of psychotherapies for depression more or less generalizable than studies of antidepressants?

PubMed

Lorenzo-Luaces, Lorenzo; Zimmerman, Mark; Cuijpers, Pim

2018-07-01

The generalizability of findings from studies exploring the efficacy of psychotherapy and antidepressants has been called into question in part because studies exclude many patients. Despite this, the frequency with which psychotherapy and antidepressant studies use specific inclusion and exclusion criteria has never been compared. We explored the exclusion criteria used in psychotherapy and pharmacotherapy studies from 1995 to 2014. Systematic literature searches were conducted in PubMed, Medline, PsycINFO, and Embase of published randomized controlled trials (RCTs) of the treatment of major depressive disorder (MDD) in adults with either antidepressants (vs. placebos) or psychotherapy (vs. placebos, treatments as usual, or other controls). Most psychotherapy (81%) and antidepressant (100%) trials excluded patients with milder symptoms as well as patients with elevated suicidal risk (56-75%), psychotic symptoms (84-88%), or substance misuse (75-81%). Psychotherapy studies were less likely to exclude patients on the basis of brief episode duration (0% vs. 48%) and co-morbid Axis I disorders (6% vs. 27%). However, psychotherapy studies excluded patients with more severe symptoms more frequently (38%) than antidepressant studies (8%). Overall, psychotherapy studies appear somewhat more inclusive than antidepressant studies. On average, antidepressant studies appear to target patients with more chronic and severe, as well as more purely depressive presentations. Copyright © 2018 Elsevier B.V. All rights reserved.

Hippocampal Perineuronal Nets Are Required for the Sustained Antidepressant Effect of Ketamine.

PubMed

Donegan, Jennifer J; Lodge, Daniel J

2017-04-01

N-methyl-D-aspartate receptor antagonists, like ketamine, produce a rapid-acting and long-lasting antidepressant effect. Although the mechanism is not completely understood, ketamine is thought to preferentially target N-methyl-D-aspartate receptors on fast-spiking parvalbumin-containing interneurons. The function of parvalbumin-containing interneurons is dependent on perineuronal nets, a specialized form of extracellular matrix that surrounds these cells. Chondroitinase was used to enzymatically degrade perineuronal nets surrounding parvalbumin-containing interneurons in the ventral hippocampus, a region that is involved in the antidepressant response to ketamine. Rats were tested on the forced swim test 30 minutes and 1 week after ketamine administration. Thirty minutes after ketamine injection, both chondroitinase-treated and control animals had a decrease in immobility. One week later, however, the antidepressant-like response observed with ketamine was completely abolished in the chondroitinase-treated animals. This suggests that parvalbumin interneuron function in the ventral hippocampus is essential for the sustained antidepressant effect of ketamine. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.

PubMed

Niciu, Mark J; Shovestul, Bridget J; Jaso, Brittany A; Farmer, Cristan; Luckenbaugh, David A; Brutsche, Nancy E; Park, Lawrence T; Ballard, Elizabeth D; Zarate, Carlos A

2018-05-01

Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters. Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n = 126) drawn from three studies received a single subanesthetic (0.5 mg/kg) ketamine infusion. Dissociative effects were measured using the Clinician-Administered Dissociative States Scale (CADSS). Antidepressant response was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). A confirmatory factor analysis established the validity of CADSS subscales (derealization, depersonalization, amnesia), and a general linear model with repeated measures was fitted to test whether subscale scores were associated with antidepressant response. Factor validity was supported, with a root mean square error of approximation of .06, a comparative fit index of .97, and a Tucker-Lewis index of .96. Across all studies and timepoints, the depersonalization subscale was positively related to HAM-D percent change. A significant effect of derealization on HAM-D percent change was observed at one timepoint (Day 7) in one study. The amnesia subscale was unrelated to HAM-D percent change. Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine's antidepressant efficacy; the possibility of Type I errors in secondary analyses. From a psychometric perspective, researchers may elect to administer only the CADSS depersonalization subscale, given that it was most closely related to antidepressant response. From a neurobiological perspective, mechanistic similarities may exist between ketamine-induced depersonalization and antidepressant response, although off-target effects cannot be excluded. Published by Elsevier B.V.

Antidepressant Studies in Parkinson’s Disease

PubMed Central

Weintraub, Daniel; Morales, Knashawn H.; Moberg, Paul J.; Bilker, Warren B.; Balderston, Catherine; Duda, John E.; Katz, Ira R.; Stern, Matthew B.

2007-01-01

The objective of this study was to determine effect sizes for both antidepressant treatment and placebo for depression in Parkinson’s disease (PD), and to compare the findings with those reported in elderly depressed patients without PD. Recent reviews have concluded that there is little empiric evidence to support the use of antidepressants in PD; however, available data has not been analyzed to determine the effect size for antidepressant treatment in PD depression. A literature review identified antidepressant studies in PD. Suitable studies were analyzed using meta-analytic techniques, and effect sizes were compared with those from antidepressant studies in elderly patients without PD. Large effect sizes were found for both active treatment and placebo in PD, but there was no difference between the two groups. In contrast, active treatment was superior to placebo in depressed elderly patients without PD. In PD, increasing age and a diagnosis of major depression were associated with better treatment response. Results also suggest that newer antidepressants are well tolerated in PD. Despite the high prevalence of depression and antidepressant use in PD, controlled treatment research has been almost non-existent. Meta-analysis results suggest a large but nonspecific effect for depression treatment in PD. In addition, PD patients may benefit less from antidepressant treatment, particularly selective serotonin reuptake inhibitors, than do elderly patients without PD. PMID:15954137

Antidepressants and benzodiazepines for panic disorder in adults.

PubMed

Bighelli, Irene; Trespidi, Carlotta; Castellazzi, Mariasole; Cipriani, Andrea; Furukawa, Toshi A; Girlanda, Francesca; Guaiana, Giuseppe; Koesters, Markus; Barbui, Corrado

2016-09-12

this limits the overall completeness of evidence. In general, based on the results of the current review, the possible role of antidepressants and benzodiazepines should be assessed by the clinician on an individual basis. The choice of which antidepressant and/or benzodiazepine is prescribed can not be made on the basis of this review only, and should be based on evidence of antidepressants and benzodiazepines efficacy and tolerability, including data from placebo-controlled studies, as a whole. Data on long-term tolerability issues associated with antidepressants and benzodiazepines exposure should also be carefully considered.The present review highlights the need for further higher-quality studies comparing antidepressants with benzodiazepines, which should be conducted with high-methodological standards and including pragmatic outcome measures to provide clinicians with useful and practical data. Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.

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

PubMed

Nguyen, Linda; Matsumoto, Rae R

2015-12-15

Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug. Copyright © 2015 Elsevier B.V. All rights reserved.

Step-wise loss of antidepressant effectiveness with repeated antidepressant trials in bipolar II depression.

PubMed

Amsterdam, Jay D; Lorenzo-Luaces, Lorenzo; DeRubeis, Robert J

2016-11-01

This study examined the relationship between the number of prior antidepressant treatment trials and step-wise increase in pharmacodynamic tolerance (or progressive loss of effectiveness) in subjects with bipolar II depression. Subjects ≥18 years old with bipolar II depression (n=129) were randomized to double-blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n=59) received continuation monotherapy for six additional months. After controlling for baseline covariates of prior medications, there was a 25% reduction in the likelihood of response to treatment with each increase in the number of prior antidepressant trials (odds ratio [OR]=0.75, unstandardized coefficient [B]=-0.29, standard error (SE)=0.12; χ 2 =5.70, P<.02], as well as a 32% reduction in the likelihood of remission with each prior antidepressant trial (OR=0.68, B=-0.39, SE=0.13; χ 2 =9.71, P=.002). This step-wise increase in pharmacodynamic tolerance occurred in both treatment conditions. Prior selective serotonin reuptake inhibitor (SSRI) therapy was specifically associated with a step-wise increase in tolerance, whereas other prior antidepressants or mood stabilizers were not associated with pharmacodynamic tolerance. Neither the number of prior antidepressants, nor the number of prior SSRIs, or mood stabilizers, were associated with an increase in relapse during continuation therapy. The odds of responding or remitting during venlafaxine or lithium monotherapy were reduced by 25% and 32%, respectively, with each increase in the number of prior antidepressant treatment trials. There was no relationship between prior antidepressant exposure and depressive relapse during continuation therapy of bipolar II disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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. © Copyright 2014 Physicians Postgraduate Press, Inc.

The Effects of Antidepressants and Quetiapine on Heart Rate Variability.

PubMed

Huang, W-L; Liao, S-C; Kuo, T B J; Chang, L-R; Chen, T-T; Chen, I-M; Yang, C C H

2016-09-01

Introduction: The autonomic effects of antidepressants and quetiapine on heart rate variability (HRV) are inconsistent based on past studies. The aim of this study was to explore their influence on the HRV of psychiatric patients without psychotic symptoms. Methods: A total of 94 patients with depression, anxiety, or somatic symptoms, were recruited into this study. Based on their medication, 4 groups were identified: the no antidepressant group (n=19), the SSRI group (using sertraline or escitalopram, n=53), the other antidepressants group (using venlafaxine or mirtazapine, n=9), and the augmentation group (AG, using an antidepressant+quetiapine, n=13). The HRV of the 4 groups were compared. The correlations between HRV and the medication(s) used were clarified. Results: Among the 4 groups, the AG had the lowest HRV with its total power (TP), very low frequency power (VLF) and low frequency power (LF) of HRV being significantly different from those of the other groups. Age and using quetiapine were found to be negatively correlated with TP, VLF and LF. With this study group, the autonomic effects of antidepressants were found not to be significant. Discussion: Among psychiatric patients without psychotic symptoms, quetiapine causes an overt decrease in HRV. © Georg Thieme Verlag KG Stuttgart · New York.

Recent Developments in Novel Antidepressants Targeting α4β2-Nicotinic Acetylcholine Receptors

PubMed Central

2015-01-01

Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promise for the development of new antidepressants. The introductory portion of this Miniperspective discusses the basic pharmacology that underpins the involvement of α4β2-nAChRs in depression, along with the structural features that are essential to ligand recognition by the α4β2-nAChRs. The remainder of this Miniperspective analyzes reported nicotinic ligands in terms of drug design considerations and their potency and selectivity, with a particular focus on compounds exhibiting antidepressant-like effects in preclinical or clinical studies. This Miniperspective aims to provide an in-depth analysis of the potential for using nicotinic ligands in the treatment of depression, which may hold some promise in addressing an unmet clinical need by providing relief from depressive symptoms in refractory patients. PMID:24901260

Understanding the prescription of antidepressants: a Qualitative study among French GPs.

PubMed

Mercier, Alain; Auger-Aubin, Isabelle; Lebeau, Jean-Pierre; Van Royen, Paul; Peremans, Lieve

2011-09-24

One-tenth of France's population is prescribed at least one antidepressant, primarily by General Practitioners. The reasons for this high prescription rate remain unclear. One-third of these prescriptions may not comply with clinical practice guidelines, and 20% are potentially unrelated to any psychiatric condition. Our aim was to explore how GPs declare they use antidepressants in daily practice and understand their reasons for prescribing them. Six focus groups including a total of 56 rural and urban GPs, with four interviews were performed. The topic guide focused on reasons for prescribing antidepressants in various primary care situations. Phenomenological analysis was performed by four researchers. Antidepressants were seen as useful and not harmful. Personal assessment based on experience and feeling determined the GPs' decisions rather than the use of scales. Twenty-four "non-psychiatric" conditions possibly leading to prescription of antidepressants in primary care were found. The GPs reported prescribing antidepressants for a wide range of conditions other than depression. The GPs' decision making process is difficult and complex. They seemed to prefer to focus on their difficulties in diagnosing depression rather than on useless overtreatment. Instead of using the guidelines criteria to detect potential cases of useful prescription, physicians tend to use their own tools based on gut feelings, knowledge of the patient and contextual issues.

Effects of BDNF polymorphisms on antidepressant action.

PubMed

Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

2010-12-01

Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

PubMed

Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

NMDA receptor subunits and associated signaling molecules mediating antidepressant-related effects of NMDA-GluN2B antagonism

PubMed Central

Kiselycznyk, Carly; Jury, Nicholas; Halladay, Lindsay; Nakazawa, Kazu; Mishina, Masayoshi; Sprengel, Rolf; Grant, Seth G.N.; Svenningsson, Per; Holmes, Andrew

2015-01-01

Drugs targeting the glutamate N-methyl-D-aspartate receptor (NMDAR) may be efficacious for treating mood disorders, as exemplified by the rapid antidepressant effects produced by single administration of the NMDAR antagonist ketamine. Though the precise mechanisms underlying the antidepressant-related effects of NMDAR antagonism remain unclear, recent studies implicate specific NMDAR subunits, including GluN2A and GluN2B, as well as the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) subunit glutamate receptor interacting molecule, PSD-95. Here, integrating mutant and pharmacological in mice, we investigated the contribution of these subunits and molecules to antidepressant-related behaviors and the antidepressant-related effects of the GluN2B blocker, Ro 25-6981. We found that global deletion of GluA1 or PSD-95 reduced forced swim test (FST) immobility, mimicking the antidepressant-related effect produced by systemically administered Ro 25-6981 in C57BL/6J mice. Moreover, the FST antidepressant-like effects of systemic Ro 25-6981 were intact in mutants with global GluA1 deletion or GluN1 deletion in forebrain interneurons, but were absent in mutants constitutively lacking GluN2A or PSD-95. Next, we found that microinfusing Ro 25-6981 into the medial prefrontal cortex (mPFC), but not basolateral amygdala, of C57BL/6J mice was sufficient to produce an antidepressant-like effect. Together, these findings extend and refine current understanding of the mechanisms mediating antidepressant-like effects produced by NMDAR-GluN2B antagonists, and may inform the development of a novel class of medications for treating depression that target the GluN2B subtype of NMDAR. PMID:25800971

Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands

PubMed Central

Chilmonczyk, Zdzisław; Bojarski, Andrzej Jacek; Pilc, Andrzej; Sylte, Ingebrigt

2015-01-01

Serotonin (5-HT) is a monoamine neurotransmitter that plays an important role in physiological functions. 5-HT has been implicated in sleep, feeding, sexual behavior, temperature regulation, pain, and cognition as well as in pathological states including disorders connected to mood, anxiety, psychosis and pain. 5-HT1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT1A agonists could form a new class of antidepressant drugs, and mixed 5-HT1A receptor ligands/serotonin transporter (SERT) inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT1A receptors can activate several different biochemical pathways and signal through both G protein-dependent and G protein-independent pathways. The variables that affect the multiplicity of 5-HT1A receptor signaling pathways would thus result from the summation of effects specific to the host cell milieu. Moreover, receptor trafficking appears different at pre- and postsynaptic sites. It should also be noted that the 5-HT1A receptor cooperates with other signal transduction systems (like the 5-HT1B or 5-HT2A/2B/2C receptors, the GABAergic and the glutaminergic systems), which also contribute to its antidepressant and/or anxiolytic activity. Thus identifying brain specific molecular targets for 5-HT1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies. PMID:26262615

Antidepressant Medication Use, Depression and the Risk of Preeclampsia

PubMed Central

Avalos, Lyndsay Ammon; Chen, Hong Y.; Li, De-Kun

2018-01-01

Objective To assess the effects of depression and antidepressant medication use during pregnancy on the risk of preeclampsia. Methods We conducted a retrospective, population-based cohort study linking automated clinical and pharmacy databases including comprehensive electronic medical records of 21,589 pregnant Kaiser Permanente Northern California members between 2010 and 2012. Results The overall risk of preeclampsia was 4.5%. The timing of antidepressant medication exposure was an important factor. A significant increase in the risk of preeclampsia emerged for women with a depression diagnosis who took antidepressant medications during the second trimester compared to women with untreated depression (adjusted Relative Risk (aRR): 1.6, 95% CI: 1.06, 2.39), and to women without depression (aRR: 1.70, 95% CI: 1.30, 2.23). Similar associations existed for women who took antidepressant medications, but without depression. In contrast, depressed women with psychotherapy showed no increased risk of preeclampsia compared to women with untreated depression or no depression. There was also a statistically significant relationship between the duration of antidepressant medication use and preeclampsia. The observed association appeared stronger for SSRI use, although a non-significant trend was also noted for use of NDRIs and SNRIs. Conclusion Study findings suggest that the antidepressant use during pregnancy may increase the risk of preeclampsia, especially the use during the second trimester. PMID:25778691

Scopolamine rapidly increases mTORC1 signaling, synaptogenesis, and antidepressant behavioral responses

PubMed Central

Voleti, Bhavya; Navarria, Andrea; Liu, Rong-Jian; Banasr, Mounira; Li, Nanxin; Terwilliger, Rose; Sanacora, Gerard; Eid, Tore; Aghajanian, George; Duman, Ronald S.

2013-01-01

Background Clinical studies report that scopolamine, an acetylcholine muscarinic receptor antagonist, produces rapid antidepressant effects in depressed patients, but the mechanisms underlying the therapeutic response have not been determined. The present study examines the role of the mammalian target of rapamycin complex 1 (mTORC1) and synaptogenesis, which have been implicated in the rapid actions of NMDA receptor antagonists. Methods The influence of scopolamine on mTORC1 signaling was determined by analysis of the phosphorylated and activated forms of mTORC1 signaling proteins in the prefrontal cortex (PFC). The numbers and function of spine synapses were analyzed by whole cell patch clamp recording and 2-photon image analysis of PFC neurons. The actions of scopolamine were examined in the forced swim test in the absence or presence of selective mTORC1 and AMPA receptor inhibitors. Results The results demonstrate that a single, low dose of scopolamine rapidly increases mTORC1 signaling and the number and function of spine synapses in layer V pyramidal neurons in the PFC. Scopolamine administration also produces an antidepressant response in the forced swim test that is blocked by pretreatment with the mTORC1 inhibitor or by a glutamate AMPA receptor antagonist. Conclusions Taken together, the results demonstrate that the antidepressant actions of scopolamine require mTORC1 signaling and are associated with increased glutamate transmission, and synaptogenesis, similar to NMDA receptor antagonists. These findings provide novel targets for safer and more efficacious rapid acting antidepressant agents. PMID:23751205

On categorizing gestational, birth, and neonatal complications following late pregnancy exposure to antidepressants: the prenatal antidepressant exposure syndrome.

PubMed

Gentile, Salvatore

2010-03-01

Late in utero exposure to antidepressants has been suspected of adversely impacting pregnancy outcome and compromising neonatal adaptation. Hence, the necessity exists to analyze published information on antidepressant use during late pregnancy to individuate potential recurrent patterns of iatrogenic complications. Computerized searches on MEDLINE, PsycINFO, ENBASE, and Cochrane Library through February 10, 2010 were performed for selecting literature information and investigating the safety of antidepressants when used during late pregnancy. Antidepressant treatment during late pregnancy may increase the rates of poor pregnancy outcome and neonatal withdrawal/toxic reactions. Because both gestational complications and neonatal adverse events acknowledge the same etiology, the author suggests including such iatrogenic events under the definition of prenatal antidepressant exposure syndrome, in order to increase clinicians' awareness about the spectrum of risks which may concern the mother-infant pair when antidepressant treatment is deemed indispensable during late pregnancy.

The effect of antidepressants on fertility.

PubMed

Casilla-Lennon, Marianne M; Meltzer-Brody, Samantha; Steiner, Anne Z

2016-09-01

Information on the effects of different pharmaceuticals on fertility is sparse. Human and animal models indicate that antidepressant use could have a negative effect on fertility through alteration of levels of the neurosteroid, allopregnanolone. The objective of this study is to assess the effects of antidepressants on the natural fertility in women. A secondary analysis of data from Time to Conceive, a prospective cohort study, was conducted. Women ages 30 to 44 years without a history of infertility, early in their attempts to conceive, were followed with standardized pregnancy testing until pregnancy was detected. Medication use was assessed at enrollment, daily for up to 4 months, and then monthly. For this analysis, discrete time regression models were created to calculate the association between antidepressant use and fecundability. Potential confounders-age, body mass index, caffeine, alcohol use, and education-were included in all models. Ninety-two (9.6%) of 957 women reported antidepressant use while attempting to conceive. Women taking antidepressants were more likely to be non-Hispanic Caucasian (91% vs 75%, P < .01) and to consume alcoholic beverages (74% vs 61%, P < .01). Antidepressant use at enrollment had an adjusted fecundability ratio (FR) of 0.86 (95% confidence interval [CI], 0.63-1.20). However, time-varying analyses suggested that antidepressant use in a given cycle is associated with a reduced probability of conceiving in that cycle (adjusted FR, 0.75; 95% CI, 0.53-1.06). After adjusting for history of depression or restricting the analysis to women who reported a history of depression, the association between antidepressant use and decreased fecundability remained [adjusted FR, 0.66 (95% CI, 0.45-0.97) and (adjusted FR, 0.64; 95% CI, 0.43-0.94), respectively]. Our data suggest that antidepressants may reduce the probability of a woman with a history of depression to conceive naturally. Future studies are needed to differentiate the extent

BDNF — a key transducer of antidepressant effects

PubMed Central

Björkholm, Carl; Monteggia, Lisa M.

2016-01-01

How do antidepressants elicit an antidepressant response? Here, we review accumulating evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) serves as a transducer, acting as the link between the antidepressant drug and the neuroplastic changes that result in the improvement of the depressive symptoms. Over the last decade several studies have consistently highlighted BDNF as a key player in antidepressant action. An increase in hippocampal and cortical expression of BDNF mRNA parallels the antidepressant-like response of conventional antidepressants such as SSRIs. Subsequent studies showed that a single bilateral infusion of BDNF into the ventricles or directly into the hippocampus is sufficient to induce a relatively rapid and sustained antidepressant-like effect. Importantly, the antidepressant-like response to conventional antidepressants is attenuated in mice where the BDNF signaling has been disrupted by genetic manipulations. Low dose ketamine, which has been found to induce a rapid antidepressant effect in patients with treatment-resistant depression, is also dependent on increased BDNF signaling. Ketamine transiently increases BDNF translation in hippocampus, leading to enhanced synaptic plasticity and synaptic strength. Ketamine has been shown to increase BDNF translation by blocking NMDA receptor activity at rest, thereby inhibiting calcium influx and subsequently halting eukaryotic elongation factor 2 (eEF2) kinase leading to a desuppression of protein translation, including BDNF translation. The antidepressant-like response of ketamine is abolished in BDNF and TrkB conditional knockout mice, eEF2 kinase knockout mice, in mice carrying the BDNF met/met allele, and by intra-cortical infusions of BDNF-neutralizing antibodies. In summary, current data suggests that conventional antidepressants and ketamine mediate their antidepressant-like effects by increasing BDNF in forebrain regions, in particular the hippocampus, making BDNF an

Antidepressant Use Is Associated With an Increased Risk of Developing Microbleeds.

PubMed

Akoudad, Saloua; Aarts, Nikkie; Noordam, Raymond; Ikram, M Arfan; Tiemeier, Henning; Hofman, Albert; Stricker, Bruno H; Vernooij, Meike W; Visser, Loes E

2016-01-01

Serotonin-specific antidepressants may increase the risk of adverse bleeding events. In a previous cross-sectional study, we did not observe an association between antidepressant use and presence of subclinical cerebral bleedings. In this study, we investigated longitudinally whether antidepressant use is associated with an increased risk of new subclinical cerebral microbleeds. In total, 2559 participants aged ≥45 years of the population-based Rotterdam Study, all without microbleeds at baseline, underwent baseline and repeat brain magnetic resonance imaging between 2005 and 2013 (mean time interval, 3.9 years; SD, 0.5) to determine the incidence of microbleeds. Antidepressant use (yes versus no) was assessed between baseline and follow-up scan. In additional analyses, antidepressants were classified as low, intermediate, or high affinity for the serotonin transporter, and alternatively as selective serotonin reuptake inhibitors or non-selective serotonin reuptake inhibitors. We used multivariable logistic regression models to investigate the association of antidepressants with incident microbleeds. Antidepressant use was associated with a higher cerebral microbleed incidence (odds ratio, 2.22; 95% confidence interval, 1.31-3.76) than nonuse. When stratified by affinity for the serotonin transporter, intermediate serotonin affinity antidepressant use was associated with an increased risk of developing microbleeds (odds ratio, 3.07; 95% confidence interval, 1.53-6.17). Finally, selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor use were both associated with increased microbleed incidence. Antidepressant use was associated with an increased risk of developing microbleeds. Our results may support findings from previous clinical studies about increased intracranial and extracranial bleeding risk in antidepressant users. © 2015 American Heart Association, Inc.

Antidepressant poisoning deaths in New Zealand for 2001.

PubMed

Reith, David; Fountain, John; Tilyard, Murray; McDowell, Rebecca

2003-10-24

To compare the rates of death per volume of drug dispensed for antidepressants in New Zealand. Deaths from antidepressant poisonings were identified from the reports of coronial inquiries for New Zealand in 2001. Prescriptions for antidepressant medications were identified from the PharmHouse database from 1 January 2001 to 31 December 2001. The rates of deaths (95% CI) per prescription, tablet/capsule or defined daily dose were calculated for individual antidepressants and classes of antidepressant. There were 200 poisoning deaths recorded in the database for New Zealand in 2001. Antidepressants were involved in 41 deaths, and death was attributed to an antidepressant in 23 cases. There were 5.52 (95% CI 3.85-7.68) deaths per 100 000 prescriptions for tricyclic antidepressants (TCAs) and 2.51 (1.57-3.79) deaths per 100 000 prescriptions for selective serotonin reuptake inhibitors (SSRIs). There was marked variability in rates of death per volume of drug dispensed between individual antidepressants. SSRIs have lower rates of death per volume of drug dispensed than TCAs and there is also variation in these rates within these classes of drugs. Toxicity in overdose should be considered when prescribing antidepressants.

Utilizing Education and Perspective Taking to Remediate the Stigma of Taking Antidepressants.

PubMed

Martinez, Larry R; Xu, Shi; Hebl, Michelle

2018-05-01

The incidence of depression has been increasing. One of the best interventions for depression is taking antidepressant medications. However, the stigma of taking antidepressants has been shown to be a barrier not only to seeking an antidepressant regimen but also adhering to it. This may have negative consequences for people who suffer from depression. Thus, in two studies, we investigate the incidence of felt stigma of taking antidepressants among clinically depressed individuals who take antidepressants and the effectiveness of two possible interventions to reduce this stigma among others. Study 1 revealed that stigma toward individuals who take antidepressants is a reality, either because people were not educated about depression and antidepressants, or because they did not show empathy or did not take on perspectives from the victim's point-of-view. Based on these results, we used an experimental design in Study 2 to investigate the effects of education and perspective-taking interventions in diminishing the stigma of taking antidepressants. These results suggest that participant gender played a moderating role in the effectiveness of education and perspective taking, such that a combination of the two interventions resulted in lower stigma for men but not for women. These results suggest that people can be trained (using a simple, low-fidelity intervention) to be more accepting of antidepressant use among their friends, family members, and colleagues, resulting in better outcomes for those who benefit from taking antidepressants.

VGF function in depression and antidepressant efficacy.

PubMed

Jiang, C; Lin, W-J; Sadahiro, M; Labonté, B; Menard, C; Pfau, M L; Tamminga, C A; Turecki, G; Nestler, E J; Russo, S J; Salton, S R

2017-11-21

Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes. Mice with reduced VGF levels in the germ line (Vgf+/-) or in dHc (AAV-Cre-injected floxed mice) showed increased susceptibility to CSDS and impaired responses to ketamine treatment in the forced swim test. Floxed mice with conditional pan-neuronal (Synapsin-Cre) but not those with forebrain (αCaMKII-Cre) Vgf ablation displayed increased susceptibility to subthreshold social defeat stress, suggesting that neuronal VGF, expressed in part in inhibitory interneurons, regulates depression-like behavior. Acute antibody-mediated sequestration of VGF-derived C-terminal peptides AQEE-30 and TLQP-62 in dHc induced pro-depressant effects. Conversely, dHc TLQP-62 infusion had rapid antidepressant efficacy, which was reduced in BDNF floxed mice injected in dHc with AAV-Cre, and in NBQX- and rapamycin-pretreated wild-type mice, these compounds blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling, respectively. VGF is therefore a critical modulator of depression-like behaviors in dHc and NAc. In hippocampus, the antidepressant response to ketamine is associated with rapid VGF translation, is impaired by reduced VGF expression, and as previously reported, requires coincident, rapid BDNF translation and release.Molecular Psychiatry advance online publication, 21 November

Rapid Antidepressant Actions of Scopolamine: Role of Medial Prefrontal Cortex and M1-subtype Muscarinic Acetylcholine Receptors

PubMed Central

Navarria, Andrea; Wohleb, Eric S.; Voleti, Bhavya; Ota, Kristie T.; Dutheil, Sophie; Lepack, Ashley E.; Dwyer, Jason M.; Fuchikami, Manabu; Becker, Astrid; Drago, Filippo; Duman, Ronald S.

2015-01-01

Clinical studies demonstrate that scopolamine, a nonselective muscarinic acetycholine receptor (mAchR) antagonist, produces rapid therapeutic effects in depressed patients, and preclinical studies report that the actions of scopolamine require glutamate receptor activation and the mechanistic target of rapamycin complex 1 (mTORC1) in the medial prefrontal cortex (mPFC). The present study extends these findings to determine the role of the mPFC and specific muscarinic acetylcholine receptor (M-AchR) subtypes in the actions of scopolamine. Administration of scopolamine increases the activity marker Fos in the mPFC, including the infralimbic (IL) and prelimbic (PrL) subregions. Microinfusions of scopolamine into either the IL or PrL produced significant antidepressant responses in the forced swim test, and neuronal silencing of IL or PrL blocked the antidepressant effects of systemic scopolamine. The results also demonstrate that systemic administration of a selective M1-AChR antagonist, VU0255035 produced an antidepressant response and stimulated mTORC1 signaling in the PFC, similar to the actions of scopolamine. Finally, we used a chronic unpredictable stress model as a more rigorous test of rapid antidepressant actions, and found that scopolamine or VU0255035 administration blocked the anhedonic response caused by CUS, an effect that requires chronic administration of typical antidepressants. Taken together, these findings indicate that mPFC is a critical mediator of the behavioral actions of scopolamine, and identify the M1-AChR as a therapeutic target for the development of novel and selective rapid-acting antidepressants. PMID:26102021

Rapid antidepressant actions of scopolamine: Role of medial prefrontal cortex and M1-subtype muscarinic acetylcholine receptors.

PubMed

Navarria, Andrea; Wohleb, Eric S; Voleti, Bhavya; Ota, Kristie T; Dutheil, Sophie; Lepack, Ashley E; Dwyer, Jason M; Fuchikami, Manabu; Becker, Astrid; Drago, Filippo; Duman, Ronald S

2015-10-01

Clinical studies demonstrate that scopolamine, a non-selective muscarinic acetylcholine receptor (mAchR) antagonist, produces rapid therapeutic effects in depressed patients, and preclinical studies report that the actions of scopolamine require glutamate receptor activation and the mechanistic target of rapamycin complex 1 (mTORC1). The present study extends these findings to determine the role of the medial prefrontal cortex (mPFC) and specific muscarinic acetylcholine receptor (M-AchR) subtypes in the actions of scopolamine. The administration of scopolamine increases the activity marker Fos in the mPFC, including the infralimbic (IL) and prelimbic (PrL) subregions. Microinfusions of scopolamine into either the IL or the PrL produced significant antidepressant responses in the forced swim test, and neuronal silencing of IL or PrL blocked the antidepressant effects of systemic scopolamine. The results also demonstrate that the systemic administration of a selective M1-AChR antagonist, VU0255035, produced an antidepressant response and stimulated mTORC1 signaling in the PFC, similar to the actions of scopolamine. Finally, we used a chronic unpredictable stress model as a more rigorous test of rapid antidepressant actions and found that a single dose of scopolamine or VU0255035 blocked the anhedonic response caused by CUS, an effect that requires the chronic administration of typical antidepressants. Taken together, these findings indicate that mPFC is a critical mediator of the behavioral actions of scopolamine and identify the M1-AChR as a therapeutic target for the development of novel and selective rapid-acting antidepressants. Copyright © 2015 Elsevier Inc. All rights reserved.

Agomelatine, the first melatonergic antidepressant: discovery, characterization and development.

PubMed

de Bodinat, Christian; Guardiola-Lemaitre, Béatrice; Mocaër, Elisabeth; Renard, Pierre; Muñoz, Carmen; Millan, Mark J

2010-08-01

Current management of major depression, a common and debilitating disorder with a high social and personal cost, is far from satisfactory. All available antidepressants act through monoaminergic mechanisms, so there is considerable interest in novel non-monoaminergic approaches for potentially improved treatment. One such strategy involves targeting melatonergic receptors, as melatonin has a key role in synchronizing circadian rhythms, which are known to be perturbed in depressed states. This article describes the discovery and development of agomelatine, which possesses both melatonergic agonist and complementary 5-hydroxytryptamine 2C (5-HT2C) antagonist properties. Following comprehensive pharmacological evaluation and extensive clinical trials, agomelatine (Valdoxan/Thymanax; Servier) was granted marketing authorization in 2009 for the treatment of major depression in Europe, thereby becoming the first approved antidepressant to incorporate a non-monoaminergic mechanism of action.

Antidepressant use during pregnancy and childhood cancer in the offspring.

PubMed

Momen, Natalie C; Munk-Olsen, Trine; Li, Jiong; Ingstrup, Katja G; Olsen, Jørn; Bergink, Veerle; Liu, Xiaoqin

2018-01-01

Antidepressant use during pregnancy has been increasing in recent years. We evaluated whether in utero exposure to antidepressants increased the risk of childhood cancer. This population-based cohort study using national registers in Denmark comprised 915 128 liveborn singletons during 1998-2012. We categorised children into three mutually exclusive exposure groups according to maternal redemption of an antidepressant prescription from 2 years before pregnancy until delivery of the index child: Unexposed (N = 863 033), prior user (use before but not during pregnancy) (N = 30 607), and use during pregnancy (N = 21 488). The children were followed from birth until first diagnosis of cancer, death, emigration, or December 31, 2012, whichever came first. The children were followed maximum 14.9 years and contributed to 6.9 × 10 6 person-years at risk. We estimated hazard ratios (HRs) of cancer using Cox regression with 95% confidence intervals (CIs). In total, 1298 (0.1%) children were diagnosed with cancer. Antidepressant use during pregnancy was not associated with a significantly increased risk of childhood cancer in general; the HR was 1.03 (95% CI, 0.63-1.68), compared to children born by mothers who discontinued antidepressant use prior to pregnancy. The association between in utero exposure to antidepressants and childhood cancer did not depend on type or duration of antidepressant use. There was no strong evidence indicating a higher risk of leukaemia or nervous system tumours among children exposed to antidepressants in utero. Antidepressant use during pregnancy was not significantly associated with childhood cancer in general nor with leukaemia or nervous system tumours in specific. Copyright © 2017 John Wiley & Sons, Ltd.

Sudden cardiac death secondary to antidepressant and antipsychotic drugs

PubMed Central

Sicouri, Serge; Antzelevitch, Charles

2008-01-01

A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use. PMID:18324881

Activation of the mGlu7 receptor elicits antidepressant-like effects in mice.

PubMed

Palucha, Agnieszka; Klak, Kinga; Branski, Piotr; van der Putten, Herman; Flor, Peter J; Pilc, Andrzej

2007-11-01

Broad evidence indicates that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. Metabotropic glutamate receptor (mGlu receptor) ligands seem to be promising agents to treat several central nervous system disorders, including psychiatric ones. The aim of our study was to investigate potential antidepressant-like activity of the first, selective, and bio-available mGlu7 receptor agonist, AMN082 (N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride), in wild-type (WT) and mGlu7 receptor knock-out (KO) mice. The forced swim test (FST) and the tail suspension test (TST) in mice were used to assess antidepressant-like activity of AMN082. We found that AMN082, administered IP, induced a dose-dependent decrease in the immobility time of WT animals in the FST and TST, suggesting antidepressant-like potency of an mGlu7 receptor agonist. Moreover, AMN082 did not change the behaviour of mGlu7 receptor KO mice compared to WT littermates in the TST, while imipramine, used as a reference control, significantly reduced their immobility, indicating an mGlu7 receptor-dependent mechanism of the antidepressant-like activity of AMN082. However, at high doses, AMN082 significantly decreased spontaneous locomotor activity of both mGlu7 receptor KO mice and WT control animals, suggesting off-target activity of AMN082 resulting in hypo-locomotion. These results strongly suggest that activation of the mGlu7 receptor elicits antidepressant-like effects.

Is retirement beneficial for mental health? Antidepressant use before and after retirement

PubMed Central

Oksanen, Tuula; Vahtera, Jussi; Westerlund, Hugo; Pentti, Jaana; Sjösten, Noora; Virtanen, Marianna; Kawachi, Ichiro; Kivimäki, Mika

2011-01-01

Background Recent studies based on self-reported data suggest that retirement may have beneficial effects on mental health, but studies using objective endpoints remain scarce. This study examines longitudinally the changes in antidepressant medication use across the 9 years spanning the transition to retirement. Methods Participants were Finnish public-sector employees: 7138 retired at statutory retirement age (76% women, mean age 61.2 years), 1238 retired early due to mental health issues (78% women, mean age 52.0 years), and 2643 retired due to physical health issues(72% women, mean age 55.4 years). Purchase of antidepressant medication four years prior to and four years after retirement year were based on comprehensive national pharmacy records in 1994-2005. Results One year before retirement, the use of antidepressants was 4% among those who would retire at statutory age, 61% among those who would retire due to mental health issues, and 14% among those who would retire due to physical health issues. Retirement-related changes in antidepressant use depended on the reason for retirement. Among old-age retirees, antidepressant medication use decreased during the transition period (age- and calendar-year-adjusted prevalence ratio for antidepressant use 1 year after vs. 1 year before retirement = 0.77 [95% confidence interval = 0.68 – 0.88]). Among those whose main reason for disability pension was mental health issues or physical health issues, there was an increasing trend in antidepressant use prior to retirement and, for mental health retirements, a decrease after retirement. Conclusions Trajectories of recorded purchases of antidepressant medication are consistent with the hypothesis that retirement is beneficial for mental health. PMID:21502864

[Mirtazapine versus other antidepressive agents for depression].

PubMed

Knud Larsen, Jens

2012-11-12

A Cochrane analysis compared efficacy and side effects of mirtazapine with other antidepressants. After six weeks of treatment no reliable difference of efficacy between mirtazapine, selective serotonin reuptake inhibitors (SSRI), noradrenaline reuptake inhibitors or tricyclic antidepressants was found. The side effects like increased sleep and weight gain were compared by treatment with mirtazapine and treatment with SSRI antidepressants. The very fact of the sleep effect and the fast onset of action have probably increased the effect size compared with SSRI antidepressants. The results of the Cochrane analysis cannot for certain be generalized to inpatients, as other studies have found tricyclic antidepressants to be especially effective.

Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism.

PubMed

Aleksandrova, Lily R; Phillips, Anthony G; Wang, Yu Tian

2017-06-01

The molecular mechanisms underlying major depressive disorder remain poorly understood, and current antidepressant treatments have many shortcomings. The recent discovery that a single intravenous infusion of ketamine at a subanesthetic dose had robust, rapid and sustained antidepressant effects in individuals with treatment-resistant depression inspired tremendous interest in investigating the molecular mechanisms mediating ketamine's clinical efficacy as well as increased efforts to identify new targets for antidepressant action. We review the clinical utility of ketamine and recent insights into its mechanism of action as an antidepressant, including the roles of N -methyl-D-aspartate receptor inhibition, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor upregulation, activation of downstream synaptogenic signalling pathways and the production of an active ketamine metabolite, hydroxynorketamine. Emerging knowledge of the molecular mechanisms underlying both ketamine's positive therapeutic and detrimental side effects will aid the development of a new generation of much-needed superior antidepressant agents.

[Antidepressants consumption in the global population in France].

PubMed

Olié, J P; Elomari, F; Spadone, C; Lépine, J P

2002-01-01

The consumption of antidepressant seems to be in France higher than in comparable countries, as well as the overall consumption of healthcare and medications. In Western countries, in recent years, the use of antidepressants has regularly increased, mainly due to the use of serotoninergic antidepressants. In France, in a week, the prevalence of antidepressant use in the overall population increased from 1.7% in 1992 to 3% in 1995. This survey addressed the overall population in the form of a representative sample focusing on subjects who indicated, at the time they were consulted, that they were taking an antidepressant. The study aimed to determine the circumstances of prescription: prescriber file, reason for prescription, type of medication prescribed, match between the prescription and the product indications stated in the marketing authorization, prescription duration and reason for discontinuing treatment. Methodology - The first stage consisted in forwarding a letter to a panel of 44 000 subjects aged 15 years or more and representative of the French population. The aim was to achieve a cross-sectional description of the population taking antidepressants. The response rate was 82% (36 036 subjects). The subjects who stated that they were taking an antidepressant were re-contacted by telephone by an interviewer trained in the use of the Composite International Diagnostic Interview - lifetime (CIDI), exploring depression and anxiety diseases with a view to potential diagnosis as per DSM criteria. Longitudinal follow-up over 8 months from the initial screening was evaluated using a monthly questionnaire on the time course of antidepressant consumption. Results - Out of 20 000 households, comprising 44 000 people aged over 15 years, 1 333 people were taking an antidepressant or had taken one in the previous 4 weeks. The sex ratio of the antidepressant consumers was 3 women to 1 man, amplifying the known sex ratio with respect to depressive disorders. The mean

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

PubMed Central

Pacchiarotti, Isabella; Bond, David J.; Baldessarini, Ross J.; Nolen, Willem A.; Grunze, Heinz; Licht, Rasmus W.; Post, Robert M.; Berk, Michael; Goodwin, Guy M.; Sachs, Gary S.; Tondo, Leonardo; Findling, Robert L.; Youngstrom, Eric A.; Tohen, Mauricio; Undurraga, Juan; González-Pinto, Ana; Goldberg, Joseph F.; Yildiz, Ayşegül; Altshuler, Lori L.; Calabrese, Joseph R.; Mitchell, Philip B.; Thase, Michael E.; Koukopoulos, Athanasios; Colom, Francesc; Frye, Mark A.; Malhi, Gin S.; Fountoulakis, Konstantinos N.; Vázquez, Gustavo; Perlis, Roy H.; Ketter, Terence A.; Cassidy, Frederick; Akiskal, Hagop; Azorin, Jean-Michel; Valentí, Marc; Mazzei, Diego Hidalgo; Lafer, Beny; Kato, Tadafumi; Mazzarini, Lorenzo; Martínez-Aran, Anabel; Parker, Gordon; Souery, Daniel; Özerdem, Ayşegül; McElroy, Susan L.; Girardi, Paolo; Bauer, Michael; Yatham, Lakshmi N.; Zarate, Carlos A.; Nierenberg, Andrew A.; Birmaher, Boris; Kanba, Shigenobu; El-Mallakh, Rif S.; Serretti, Alessandro; Rihmer, Zoltan; Young, Allan H.; Kotzalidis, Georgios D.; MacQueen, Glenda M.; Bowden, Charles L.; Ghaemi, S. Nassir; Lopez-Jaramillo, Carlos; Rybakowski, Janusz; Ha, Kyooseob; Perugi, Giulio; Kasper, Siegfried; Amsterdam, Jay D.; Hirschfeld, Robert M.; Kapczinski, Flávio; Vieta, Eduard

2014-01-01

Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications

The use of antidepressant drugs in dermatology.

PubMed

Gupta, M A; Guptat, A K

2001-11-01

This paper provides an updated review of the use of antidepressant drugs in dermatology. Some of the psychiatric disorders that are usually comorbid with dermatological disorders and respond to antidepressants include major depressive disorder, obsessive compulsive disorder, body dysmorphic disorder, social phobia and post-traumatic stress disorder usually secondary to trauma and abuse during early life. Cutaneous symptoms may be the feature of a primary psychiatric disorder, e.g. cutaneous body image problems, dermatitis artefacta, neurotic excoriations and trichotillomania, or psychiatric syndromes may be comorbid with a primary dermatological disorder such as the association of major depressive disorder or social phobia with psoriasis and obsessive compulsive disorder with acne excoriee. Some of the salient pharmacological properties of the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) antidepressants are reviewed. The review indicates that the SSRI antidepressants are potentially beneficial in the management of all the major psychiatric syndromes that are encountered in dermatological disorders. The generally more favourable side-effect profile of the SSRIs, such as lower cardiotoxicity in contrast to the TCAs, has made them the first-line agents for the treatment of depression. Furthermore, some of the pharmacological properties of the antidepressant agents that are not related to their antidepressant activity, such as the histamine H1 blocking effect of TCAs, such as doxepin, amitriptyline and trimipramine, are of benefit in dermatological conditions such as urticaria and pruritus. This paper reviews the general guidelines for use of antidepressants and salient drug-drug interactions resulting mainly from the inhibition of the cytochrome P450 (CYP) 2D6 and 3A3/4 isoenzymes by some of the SSRI antidepressants. Before prescribing an antidepressant agent, the specific guidelines, side-effect profile, drug

Quantitative determination of antidepressants and their select degradates by liquid chromatography/electrospray ionization tandem mass spectrometry in biosolids destined for land application.

PubMed

Niemi, Lydia M; Stencel, Katherine A; Murphy, Madigan J; Schultz, Melissa M

2013-08-06

Antidepressants are one of the most widely dispensed classes of pharmaceuticals in the United States. As wastewater treatment plants are a primary source of pharmaceuticals in the environment, the use of biosolids as fertilizer is a potential route for antidepressants to enter the terrestrial environment. A microsolvent extraction method, utilizing green chemistry, was developed for extraction of the target antidepressants and degradation products from biosolids, or more specifically lagoon biosolids. Liquid chromatography/tandem mass spectrometry was used for quantitative determination of antidepressants in the lagoon biosolid extracts. Recoveries from matrix spiking experiments for the individual antidepressants had an average of 96%. The limits of detection for antidepressant pharmaceuticals and degradates ranged from 0.36 to 8.0 ng/kg wet weight. The method was applied to biosolids destined for land application. A suite of antidepressants was consistently detected in the lagoon biosolid samples, and thus antidepressants are being introduced to terrestrial environments through the land application of these biosolids. Sertraline and norsertraline were the most abundant antidepressant and degradation product detected in the biosolid samples. Detected, individual antidepressant concentrations ranged from 8.5 ng/kg (norfluoxetine) to 420 ng/kg wet weight (norsertraline).

Antidepressants for Children and Teens

MedlinePlus

... come with antidepressants. Because of the risk of suicide from depression, it's difficult to establish a clear causal relationship ... children and teenagers against the real risk of suicide as a result of untreated depression. For many children and teens, antidepressants are an ...

Antidepressant-like properties of sarizotan in experimental Parkinsonism.

PubMed

Zhang, Xiaoqun; Egeland, Martin; Svenningsson, Per

2011-12-01

Depression and anxiety are common symptoms in Parkinson's disease for which there are no optimal treatments. Sarizotan, an agonist at serotonin receptors and partial agonist at dopamine D₂-like receptors, has shown antidyskinetic effects in Parkinson's disease. Based on its pharmacological profile, we hypothesized that sarizotan could also have antidepressant-like properties. Examine effects of sarizotan on behavioral and histological measures known to be regulated by established antidepressants in normal and unilaterally 6-hydroxydopamine-lesioned rats. Sarizotan was found to significantly reduce immobility in the modified forced swim test, a measure of antidepressant-like activity, but had no effects on thigmotaxis or corner time, measures of anxiety-like behavior, in the unilaterally 6-hydroxydopamine-lesioned rats. At the same dose, sarizotan counteracted L: -DOPA/benserazide-induced supersentitized rotational behavior and dyskinesias without significantly affecting L: -DOPA/benserazide-induced locomotion. At the histological level, sarizotan alone or in combination with L: -DOPA/benserazide stimulated cell proliferation, measured by bromodeoxyuridine incorporation or Ki-67 staining, both in the subgranular zone of the dentate gyrus and in the subventricular zone of the striatum in the 6-hydroxydopamine-lesioned hemisphere. Likewise, combined sarizotan and L: -DOPA/benserazide treatment stimulated doublecortin levels in the subgranular zone of the dentate gyrus. These significant effects of sarizotan in the modified forced swim test and on cell proliferation are reminiscent of those found after various antidepressant therapies. These data suggest that sarizotan may have some antidepressant-like and restorative properties in Parkinsonism.

[Metabolic safety of antidepressant medicines].

PubMed

Łężak, Wojciech; Mokros, Łukasz; Karbownik, Michał Seweryn; Witusik, Andrzej; Kosmalski, Marcin; Kowalczyk, Edward; Pietras, Tadeusz

2017-05-23

Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors

PubMed Central

Cryan, John F.; O'Leary, Olivia F.; Jin, Sung-Ha; Friedland, Julie C.; Ouyang, Ming; Hirsch, Bradford R.; Page, Michelle E.; Dalvi, Ashutosh; Thomas, Steven A.; Lucki, Irwin

2004-01-01

Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine β-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depression-related behaviors in normal and genetically modified mice. Dbh–/– mice failed to respond to the behavioral effects of various antidepressants, including the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even though they did not differ in baseline immobility from Dbh+/– mice, which have normal levels of NE. Surprisingly, the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also absent or severely attenuated in the Dbh–/– mice. In contrast, citalopram (the most selective SSRI) was equally effective at reducing immobility in mice with and without NE. Restoration of NE by using l-threo-3,4-dihydroxyphenylserine reinstated the behavioral effects of both desipramine and paroxetine in Dbh–/– mice, thus demonstrating that the reduced sensitivity to antidepressants is related to NE function, as opposed to developmental abnormalities resulting from chronic NE deficiency. Microdialysis studies demonstrated that the ability of fluoxetine to increase hippocampal serotonin was blocked in Dbh–/– mice, whereas citalopram's effect was only partially attenuated. These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs. PMID:15148402

Is Customization in Antidepressant Prescribing Associated with Acute-Phase Treatment Adherence?

PubMed

Merrick, Elizabeth L; Hodgkin, Dominic; Panas, Lee; Soumerai, Stephen B; Ritter, Grant

2012-03-01

OBJECTIVES: The objective was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centered and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. METHODS: A cross-sectional secondary data analysis examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligible Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternate measures of prescribing concentration: 1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens, and 2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. KEY FINDINGS: In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (p <.05). The Herfindahl index measure showed a trend towards a similar inverse relationship (p<.10). CONCLUSIONS: The findings provide some support for the hypothesized relationship between prescribing variation and adequate antidepressant treatment duration during the acute phase of treatment. Future work with more detailed, clinical longitudinal data could extend this inquiry to better understand the causal mechanisms using a more direct measure of customized care.

Is Customization in Antidepressant Prescribing Associated with Acute-Phase Treatment Adherence?

PubMed Central

Merrick, Elizabeth L.; Hodgkin, Dominic; Panas, Lee; Soumerai, Stephen B.; Ritter, Grant

2012-01-01

Objectives The objective was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centered and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. Methods A cross-sectional secondary data analysis examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligible Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternate measures of prescribing concentration: 1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens, and 2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. Key Findings In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (p <.05). The Herfindahl index measure showed a trend towards a similar inverse relationship (p<.10). Conclusions The findings provide some support for the hypothesized relationship between prescribing variation and adequate antidepressant treatment duration during the acute phase of treatment. Future work with more detailed, clinical longitudinal data could extend this inquiry to better understand the causal mechanisms using a more direct measure of customized care. PMID:22707982

Antidepressants versus placebo for panic disorder in adults.

PubMed

Bighelli, Irene; Castellazzi, Mariasole; Cipriani, Andrea; Girlanda, Francesca; Guaiana, Giuseppe; Koesters, Markus; Turrini, Giulia; Furukawa, Toshi A; Barbui, Corrado

2018-04-05

effect corresponds to a NNTB of 27 (95% CI 17 to 105); treating 27 people will result in one person fewer dropping out. Considering antidepressant classes, TCAs showed a benefit over placebo, while for SSRIs and serotonin-norepinephrine reuptake inhibitor (SNRIs) we observed no difference.When looking at dropouts due to adverse effects, which can be considered as a measure of tolerability, we found moderate-quality evidence showing that antidepressants as a whole are less well tolerated than placebo. In particular, TCAs and SSRIs produced more dropouts due to adverse effects in comparison with placebo, while the confidence interval for SNRI, noradrenergic reuptake inhibitors (NRI) and other antidepressants were wide and included the possibility of no difference. The identified studies comprehensively address the objectives of the present review.Based on these results, antidepressants may be more effective than placebo in treating panic disorder. Efficacy can be quantified as a NNTB of 7, implying that seven people need to be treated with antidepressants in order for one to benefit. Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts, but a less favourable profile in terms of dropout due to adverse effects. However, the tolerability profile varied between different classes of antidepressants.The choice of whether antidepressants should be prescribed in clinical practice cannot be made on the basis of this review.Limitations in results include funding of some studies by pharmaceutical companies, and only assessing short-term outcomes.Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.

Use of antidepressants in Parkinson's disease: A Swedish register-based study of over 1.5 million older people.

PubMed

Haasum, Ylva; Fastbom, Johan; Johnell, Kristina

2016-06-01

It has been suggested that depression in Parkinson's Disease (PD) is often unrecognized and undertreated. However, few previous studies have studied the use of antidepressants in a large sample of both home-dwelling and institutionalized elderly persons with PD. We aimed to study the use of antidepressants in older persons using anti-parkinson drugs (APD, used as a proxy for PD), stratified by residential setting. We analyzed individual data on age, sex, residential setting and drug use in over 1.5 million older persons in the Swedish Prescribed Drug Register on 31th of December 2013. Twenty-two percent of the home-dwellers and 50% of the institutionalized elderly persons with APD used antidepressants. Persons with APD had a higher probability of use of any antidepressant compared to persons without APD. A selective serotonin reuptake inhibitor (SSRI) was the most commonly used antidepressants in both settings followed by mirtazapin. The high use of antidepressants among older persons with APD warrants further studies on the quality of treatment of depression in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring the role of drug-metabolising enzymes in antidepressant side effects.

PubMed

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

2015-07-01

Cytochrome P450 enzymes are important in the metabolism of antidepressants. The highly polymorphic nature of these enzymes has been linked to variability in antidepressant metabolism rates, leading to hope regarding the use of P450 genotyping to guide treatment. However, evidence that P450 genotypic differences underlie the variation in treatment outcomes is inconclusive. We explored the links between both P450 genotype and serum concentrations of antidepressant with antidepressant side effects, using data from the Genome-Based Therapeutic Drugs for Depression Project (GENDEP), which is a large (n = 868), pharmacogenetic study of depressed individuals treated with escitalopram or nortriptyline. Patients were genotyped for the enzymes CYP2C19 and CYP2D6, and serum concentrations of both antidepressant and primary metabolite were measured after 8 weeks of treatment. Side effects were assessed weekly. We investigated associations between P450 genotypes, serum concentrations of antidepressants and side effects, as well as the relationship between P450 genotype and study discontinuation. P450 genotype did not predict total side effect burden (nortriptyline: n = 251, p = 0.5638, β = -0.133, standard error (SE) = 0.229; escitalopram: n = 340, p = 0.9627, β = -0.004, SE = 0.085), study discontinuation (nortriptyline n = 284, hazard ratio (HR) = 1.300, p = 0.174; escitalopram n = 376, HR = 0.870, p = 0.118) or specific side effects. Serum concentrations of antidepressant were only related to a minority of the specific side effects measured: dry mouth, dizziness and diarrhoea. In this sample where antidepressant dosage is titrated using clinical judgement, P450 genotypes do not explain differences between patients in side effects with antidepressants. Serum drug concentrations appear to only explain variability in the occurrence of a minority of specific side effects.

Increased use of antidepressants in Wuhan, China: a retrospective study from 2006 to 2012.

PubMed

Gao, Ping; Zhang, Huanian; Xu, Hua; Zhang, Chengliang; Liu, Dong

2013-01-01

The aim of this study was to investigate the trend of antidepressant use and analyze the daily cost of antidepressants in Wuhan, China. The data on the expenditure of antidepressants in Wuhan from 2006 to 2012 were retrospectively analyzed based on the defined daily dose (DDD) method recommended by the World Health Organization. In addition, the daily cost of antidepressants was calculated for the pharmacoeconomic evaluation. The overall sales of antidepressants increased by 566.7% over the 7-year period. The utilization of antidepressants increased annually from 1.067 DDDs per 1000 inhabitants per day in 2006 to 4.144 in 2012. This upward trend was mainly driven by an increase in the use of selective serotonin reuptake inhibitors (SSRIs), which accounted for about 60% of antidepressant use. Notably, the use of traditional Chinese patent medicines (TCMs) approved to treat depression in China in 2010 increased from 0.158 DDDs per 1000 inhabitants per day in 2010 to 0.305 in 2012. The daily drug cost analysis indicated that selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and other new antidepressants were more expensive while tricyclic and tetracyclic antidepressants (TCAs) had a low-cost advantage. Antidepressants were increasingly used over the study period. Among them, SSRIs followed by SNRIs were the most commonly used. After the approval for the treatment of depression, TCMs were generally accepted by physicians and patients. The low-cost advantage allowed TCAs to be used in the antidepressant therapy.

Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

PubMed

Osborn, Meagan; Rustom, Nazneen; Clarke, Melanie; Litteljohn, Darcy; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

2013-01-01

Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

Treatment Satisfaction Among Patients Taking Antidepressant Medication.

PubMed

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

2016-08-01

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

21 CFR 862.3910 - Tricyclic antidepressant drugs test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tricyclic antidepressant drugs test system. 862... Test Systems § 862.3910 Tricyclic antidepressant drugs test system. (a) Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in...

21 CFR 862.3910 - Tricyclic antidepressant drugs test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tricyclic antidepressant drugs test system. 862... Test Systems § 862.3910 Tricyclic antidepressant drugs test system. (a) Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in...

21 CFR 862.3910 - Tricyclic antidepressant drugs test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tricyclic antidepressant drugs test system. 862... Test Systems § 862.3910 Tricyclic antidepressant drugs test system. (a) Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in...

21 CFR 862.3910 - Tricyclic antidepressant drugs test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tricyclic antidepressant drugs test system. 862... Test Systems § 862.3910 Tricyclic antidepressant drugs test system. (a) Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in...

21 CFR 862.3910 - Tricyclic antidepressant drugs test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tricyclic antidepressant drugs test system. 862... Test Systems § 862.3910 Tricyclic antidepressant drugs test system. (a) Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in...

Evaluation of patients’ experiences with antidepressants reported by means of a medicine reporting system

PubMed Central

van Geffen, E. C. G.; van der Wal, S. W.; van Hulten, R.; de Groot, M. C. H.; Egberts, A. C. G.

2007-01-01

Objective To assess experiences related to antidepressant use reported to an internet-based medicine reporting system and to compare the nature of the side effects reported by patients with those reported by health care professionals (HCPs). Methods All reports submitted from May 2004 to May 2005 to an internet-based medicine reporting system in The Netherlands related to the use of antidepressants were analysed. Spontaneous reports of adverse drug reactions on antidepressants from HCPs received by The Netherlands Pharmacovigilance Centre Lareb from May 2004 to May 2005 were included for comparison. Results Of the 2232 individuals who submitted a report to the internet-based medicine reporting system, 258 submitted a report on antidepressants. Of these, 92 individuals (36%) reported on effectiveness, 40 (16%) of whom reported on ineffectiveness, and 217 (84%) submitted a report on side effects, with 202 (78%) reporting a total of 630 side effects that were experienced as negative. Fourteen individuals (5%) reported a practical issue and four (2%) reported a reimbursement issue. Of all 630 side effects reported, 48% resulted in the patient discontinuing the antidepressant therapy; of these 29% did not inform their HCP. Of all the side effects reported, 52% were perceived as “very negative”. In comparison to the side effects reported by HCPs, patients more often reported apathy, excessive sweating, ineffectiveness, somnolence, insomnia, sexual problems and weight increase. Conclusion Patients report the ineffectiveness and side effects of antidepressant therapy as negative and leading to discontinuation of the therapy. Patients and HCPs differ in the nature of the reported side effects. Patient experiences should be included in the evaluation of antidepressant treatment in clinical practice. PMID:17874086

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

PubMed

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

2015-04-01

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

[Tricyclic antidepressant therapy in headache].

PubMed

Magyar, Máté; Csépány, Éva; Gyüre, Tamás; Bozsik, György; Bereczki, Dániel; Ertsey, Csaba

2015-12-01

The two most important representatives of the primary headaches are migraine and tension-type headache. More than 10% of the population suffer from migraine and even a greater part, approximately 30-40% from tension-type headache. These two headache types have a great effect both on the individual and on the society. There are two types of therapeutic approaches to headaches: the abortive and the prophylactic therapy. Prophylactic treatment is used for frequent and/or difficult-to-treat headache attacks. Although both migraine and tension-type headache are often associated with depression, for their treatment - in contrast to the widespread medical opinion - not all antidepressants were found to be effective. Amitriptyline, which is a tricyclic antidepressant, is used as a prophylactic therapy for headache since 1968. Its efficacy has been demonstrated in several double-blind, placebo-controlled studies. Although the newer types of antidepressant, such as selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitor, have a more favorable side-effect profile than tricyclic antidepressants, their headache prophylactic effect has not been proven yet.

Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation.

PubMed

Harraz, M M; Tyagi, R; Cortés, P; Snyder, S H

2016-03-01

As traditional antidepressants act only after weeks/months, the discovery that ketamine, an antagonist of glutamate/N-methyl-D-aspartate (NMDA) receptors, elicits antidepressant actions in hours has been transformative. Its mechanism of action has been elusive, though enhanced mammalian target of rapamycin (mTOR) signaling is a major feature. We report a novel signaling pathway wherein NMDA receptor activation stimulates generation of nitric oxide (NO), which S-nitrosylates glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Nitrosylated GAPDH complexes with the ubiquitin-E3-ligase Siah1 and Rheb, a small G protein that activates mTOR. Siah1 degrades Rheb leading to reduced mTOR signaling, while ketamine, conversely, stabilizes Rheb that enhances mTOR signaling. Drugs selectively targeting components of this pathway may offer novel approaches to the treatment of depression.

Divorce and subsequent increase in uptake of antidepressant medication: a Finnish registry-based study on couple versus individual effects.

PubMed

Monden, Christiaan W S; Metsä-Simola, Niina; Saarioja, Saska; Martikainen, Pekka

2015-02-19

There is an average negative mental health effect for individuals who experience divorce. Little is known whether the pattern of such divorce effects varies within couples. We study whether the husband and wife experience similar harmful effects of divorce, whether they experience opposite effects, or whether divorce effects are purely individual. We use Finnish registry data to compare changes over a period of 5 years in antidepressant use of husbands and wives from 4,558 divorcing couples to 108,637 continuously married pairs aged 40-64, all of whom were healthy at baseline. In the period three years before and after divorce antidepressant use increases substantially. However, the likelihood of uptake of antidepressant medication during this process of divorce by one partner appears to be independent of medication uptake in the other partner. In contrast, among continuously married couples there is a clear pattern of convergence: If one partner starts to use antidepressants this increases the likelihood of uptake of antidepressant medication in the other partner. Our findings suggest that divorce effects on antidepressant use are individual and show no pattern of either convergence or divergence at the level of the couple. The increased incidence of antidepressant use associated with divorce occurs in individuals independent of what happens to their ex-partner.

Convergent mechanisms underlying rapid antidepressant action

PubMed Central

Zanos, Panos; Thompson, Scott M.; Duman, Ronald S.; Zarate, Carlos A.; Gould, Todd D.

2018-01-01

Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal and anti-anhedonic actions following a single administration to depressed patients. Proposed mechanisms of ketamine’s antidepressant action include N-methyl-D-aspartate receptor (NMDAR) modulation, GABAergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergoing pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine - pro-drug of the glycineB NMDAR antagonist 7-chlorokynurenic acid), NMDAR agonists (i.e. GLYX-13 (rapastinel)), metabotropic glutamate receptor 2/3 (mGluR2/3) antagonists, GABAA receptor modulators, and drugs acting on various serotonin receptor subtypes. These ongoing studies suggest that the future acute treatment of depression will typically occur within hours, rather than months, of treatment

A rapid, Web-based method for obtaining patient views on effects and side-effects of antidepressants.

PubMed

Rizo, Carlos; Deshpande, Amol; Ing, Alton; Seeman, Neil

2011-04-01

This project was undertaken to develop a rapid method for obtaining a widespread sample of patient views on the efficacy and side-effects of antidepressants. A Web-based method is described for rapidly and objectively obtaining patient views on the effects and side-effects of treatment with antidepressants. The method entails a systematized search of many URLs (Uniform Resource Locators, or Web page addresses), using keywords and phrases to extract the named drug and symptom that are reliably relevant to the medication being taken by the individual reporting the experience online. Unwanted medical conditions (e.g., cancer) are excluded. Three successive searches of thousands of Web pages revealed a cumulative total of 835 "mentions" of patient experience on duloxetine, 756 for venlafaxine, 637 for citalopram, 636 for sertraline, 559 for paroxetine, 457 for fluoxetine, 318 for desvenlafaxine, 289 for fluvoxamine, and 210 for mirtazapine, in association with various symptoms. A comparison of the associated symptoms for each of the antidepressants found that the prevalence of the combined factor of fatigue, drowsiness, tiredness or lethargy ranged from 6.4±0.8% down to 2.9±0.15% of the mentions, where the S.E. was derived from three repeats of the Web-based analysis. The prevalence of dizziness or vertigo ranged from 7.6±0.8% down to 1.9±0.3% of the mentions. Given the increasing number of patient narratives about drug experiences on open-access Web forums, this rapid novel method will have increasing utility in post-marketing surveillance and in comparing the effects of psychiatric medications. Copyright © 2010 Elsevier B.V. All rights reserved.

Differences in prescription rates and odds ratios of antidepressant drugs in relation to individual hormonal contraceptives: a nationwide population-based study with age-specific analyses.

PubMed

Lindberg, Malou; Foldemo, Anniqa; Josefsson, Ann; Wiréhn, Ann-Britt

2012-04-01

To examine, among young women, the association of individual hormonal contraceptives, within two broad groupings, with antidepressant therapy. In a nationwide register-based study, we examined the prescription rates of antidepressant drugs in relation to individual combined hormonal and progestin-only contraceptives among Swedish women aged 16-31 years (N = 917,993). Drug data were obtained from the Swedish Prescribed Drug Register for the period 1 July 2005-30 June 2008. Data on the total population of women aged 16-31 in 2008 were obtained from the Total Population Register of Statistics Sweden. The proportion of women using both hormonal contraception and antidepressants, and odds ratios (ORs) for antidepressant use for hormonal contraceptive users versus non-users, were calculated, the latter by logistic regression, for each formulation. The highest antidepressant OR in all age groups, particularly in the 16-19 years age group, related to medroxyprogesterone-only, followed by etonogestrel-only, levonorgestrel-only and ethinylestradiol/norelgestromin formulations. Oral contraceptives containing ethinylestradiol combined with lynestrenol or drospirenone had considerably higher ORs than other pills. ORs significantly lower than 1 were observed when ethinylestradiol was combined with norethisterone, levonorgestrel or desogestrel. The association between use of hormonal contraceptives and antidepressant drugs varies considerably within both the combined hormonal contraceptive and the progestin-only groups.

Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands: choice of antidepressant and dose.

PubMed

de Vries, Ymkje Anna; de Jonge, Peter; Kalverdijk, Luuk; Bos, Jens H J; Schuiling-Veninga, Catharina C M; Hak, Eelko

2016-11-01

The Dutch guideline for the treatment of depression in young people recommends initiating antidepressant treatment with fluoxetine, as the evidence for its efficacy is strongest and the risk of suicidality may be lower than with other antidepressants. Furthermore, low starting doses are recommended. We aimed to determine whether antidepressant prescriptions are in accord with guidelines. A cohort of young people aged between 6 and 17 at the time of antidepressant initiation was selected from IABD, a Dutch pharmacy prescription database. The percentage of prescriptions for each antidepressant was determined. Starting and maintenance doses were determined and compared with recommendations for citalopram, fluoxetine, fluvoxamine, and sertraline. During the study period, 2942 patients initiated antidepressant treatment. The proportion of these young people who were prescribed fluoxetine increased from 10.1 % in 1994-2003 to 19.7 % in 2010-2014. However, the most commonly prescribed antidepressants were paroxetine in 1994-2003 and citalopram in 2004-2014. The median starting and maintenance doses were ≤0.5 DDD/day for tricyclic antidepressants and 0.5-1 DDD/day for SSRIs and other antidepressants. Starting doses were guideline-concordant 58 % of the time for children, 31 % for preteens, and 16 % for teens. Sixty percent of teens were prescribed an adult starting dose. In conclusion, guideline adherence was poor. Physicians preferred citalopram over fluoxetine, in contrast to the recommendations. Furthermore, although children were prescribed a low starting dose relatively frequently, teens were often prescribed an adult starting dose. These results suggest that dedicated effort may be necessary to improve guideline adherence.

Trends in the prescribing of antidepressants following acute myocardial infarction, 1993-2002.

PubMed

Benazon, Nili R; Mamdani, Muhammad M; Coyne, James C

2005-01-01

There has been a substantial increase in the prescribing of antidepressants on a population basis and in particular serotonin reuptake inhibitors (SSRIs). SSRIs have lower cardiac toxicity than tricyclic antidepressants (TCAs). We examined how the prescribing of antidepressants to patients post-myocardial infarction (MI) changed in the decade 1993 to 2002, including the proportion accounted for by TCAs. A population-based study cross-sectional time series analysis was conducted in which quarterly antidepressant prescription data were obtained for 1993 to 2002 for elderly Ontarians who had experienced an MI, as well as for age- and sex-matched controls with no history of MI. The number of patients varied per quarter, for a total of 68,870 post-MI patients and an equal number of matched controls. Covariates included age, gender, income, and number of medications dispensed in the past year. Post-MI patients were more likely to receive an antidepressant relative to controls, with an overall odds ratio (OR) of 1.34; 95% confidence interval (CI), 1.29-1.38. However, with adjustment for the number of medications received, post-MI patients were 20% less likely to receive an antidepressant relative to controls, adjusted OR = 0.81; 95% CI, 0.78-0.84. The proportion of antidepressants prescribed to post-MI patients accounted for by TCAs decreased, but the proportion of post-MI patients receiving a TCA remained stable at approximately 6%. Increases in the prescription of antidepressants, and in particular SSRIs, to post-MI patients reflect general population trends rather than any special importance attached to treating post-MI depression. The apparent greater likelihood that post-MI patients will receive an antidepressant is reversed when total number of medications is controlled, a proxy for medical utilization and comorbidity.

Potential antidepressant properties of IDN 5491 (hyperforin-trimethoxybenzoate), a semisynthetic ester of hyperforin.

PubMed

Cervo, Luigi; Mennini, Tiziana; Rozio, Marco; Ekalle-Soppo, Charlotte Blanche; Canetta, Alessandro; Burbassi, Silvia; Guiso, Giovanna; Pirona, Lorenza; Riva, Antonella; Morazzoni, Paolo; Caccia, Silvio; Gobbi, Marco

2005-03-01

Hyperforin is one of the possible active principles mediating the antidepressant activity of Hypericum perforatum L. extracts. The ester derivative IDN 5491 (hyperforin-trimethoxybenzoate) showed antidepressant-like properties in the forced swimming test (FST) in rats, with no effect on open-field activity, when given as three intraperitoneal injections in 24 h at 3.125 and 6.25 mg/kg. The plasma concentrations of IDN 5491 were 30-50 microM, and those of hyperforin much lower but still close to those after effective doses of hyperforin-dicyclohexylammonium and Hypericum extract. This suggests that hyperforin plays a role in the antidepressant-like effect of the ester and of Hypericum extract. In vitro binding and uptake data showed that IDN 5491 is inactive on a wide panel of CNS targets at a concentration (14 microM) much higher than that measured in the brain of treated rats (0.3 microM). Like the extract, the antidepressant-like effect of IDN 5491 was blocked by (-)-sulpiride, a selective D2 receptor antagonist and by BD-1047, a selective sigma1 antagonist. Ex-vivo binding studies showed that brain sigma1 receptors are occupied after in vivo treatment with IDN 5491, possibly by an unknown metabolite or by endogenous ligand induced by hyperforin.

How does media coverage effect the consumption of antidepressants? A study of the media coverage of antidepressants in Danish online newspapers 2010-2011.

PubMed

Green Lauridsen, Michael; Kälvemark Sporrong, Sofia

2018-07-01

The news media has become a major source of health information for the public, and hence vital in the individuals' opinions and decisions about health topics. The first decrease in the usage of antidepressants in Denmark in over a decade happened alongside an intensive period of media coverage about antidepressants. The aim of this study was to examine the Danish media's coverage of antidepressants during 2010-2011 in order to explore what influence it could have had on the change in the use of antidepressants. Three media theoretical concepts, agenda-setting, priming and framing, were used to explain the media influence with regard to which subject the public should think about, which criteria the public should judge the subject by, and how the public should think about the subject. All articles about antidepressants in the main Danish Internet newspapers from 2010-2011 were analyzed via quantitative and qualitative content analyses. The quantitative analysis was used to determine agenda-setting (number of articles) and, by coding articles, how priming was used in the descriptions of antidepressants. In the qualitative analysis, all articles were analyzed and condensed to determine which frames were used. Quantitative results: 271 articles were included. Agenda-setting was shown by a marked increase in the number of articles about antidepressants. Eight main codes were identified, with the negatively-associated side effects being the major one, thereby priming the public to use side effects as a criterion when judging antidepressants. Qualitative results: Two main frames were identified: 1) economic profits vs. medicine safety, and 2) the necessity of antidepressants. Both frames presented a critical view on antidepressants. It is believed that the media's agenda-setting, priming and framing of antidepressants led the public to have a more skeptical view on antidepressants, which may have probably contributed to a decrease in the usage of antidepressants

Study design features affecting outcome in antidepressant trials.

PubMed

Henkel, Verena; Casaulta, Flurina; Seemüller, Florian; Krähenbühl, Stephan; Obermeier, Michael; Hüsler, Jürg; Möller, Hans-Jürgen

2012-12-10

A key issue in the approval process of antidepressants is the inconsistency of results between antidepressant clinical phase III trials. Identifying factors influencing efficacy data is needed to facilitate interpretation of the results. We reviewed data packages submitted as new drug applications to Swissmedic focusing on pivotal, short-term antidepressant trials. Included studies used HAMD-17 or HAMD-21 as primary measures and enrolled patients aged 18-65 years with a diagnosis of major depression. Due to the hierarchical structure of the data a mixed-effect regression model has been applied with responder rates as primary outcome criterion. Random intercepts were estimated for the different trials, while study design factors were assigned as explanatory fixed effects. The final dataset was based upon 35 study reports with a total of N=10,835 patients. Significant results were found for study arm (placebo vs. active compound, p<0.001), sample size (p=0.002), duration of treatment (p=0.024), two or more active treatment arms (p=0.022) and the individual drug (p=0.029). Furthermore, a tendency to an association with the outcome was observed for baseline disease severity (p=0.077) and possibility of dosing adaptation (p=0.076). Due to strict confidentiality agreements, individual drugs are not reported here. Further research should consider additional variables that might have an impact on the results of antidepressant trials. Efficacy data in antidepressant trials is significantly affected by various factors. These factors and their potentially confounding role have to be considered in the interpretation of the results. Copyright © 2012 Elsevier B.V. All rights reserved.

Occurrence of antidepressant residues in the sewage-impacted Vistula and Utrata rivers and in tap water in Warsaw (Poland).

PubMed

Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

2014-06-01

Antidepressants, even at low concentrations, can reveal some adverse effects on aquatic life due to disturbing homeostasis throughout the central and peripheral nervous system both in vertebrates and invertebrates. To date there have not been any reports regarding the presence of these pharmaceuticals in surface and tap waters in Eastern Europe. Therefore the aim of this study was to determine the presence of 21 antidepressant pharmaceuticals at specific points of the main Polish river - the Vistula, a smaller river of the Warsaw region - the Utrata, as well as in tap water samples of Warsaw. Samples were collected twice at one month intervals and analysed using solid-phase extraction (SPE) technique coupled with the liquid chromatography-electrospray ionisation-tandem mass spectrometer (LC-MS/MS) method operated under the multiple reaction monitoring mode (MRM). This is the first study where active compounds such as moclobemid or trazodone in the environment have been investigated. Environmental risk assessment of antidepressants in Poland was estimated on the basis of annuals sale data extracted from the NFZ (Narodowy Fundusz Zdrowia-National Health Service) base of reimbursed pharmaceuticals(1). Predicted environmental concentration (PEC) of target pharmaceuticals were compared with their measured concentration (MEC). Moreover, the application of the EMEA/CHMP guideline for environmental risk assessment of the antidepressants was discussed. The highest concentration of antidepressants was observed in the small river Utrata. In tap water only trace amounts of antidepressants including citalopram (up to 1.5ng/l), mianserin (up to 0.9ng/l), sertraline (<3.1ng/l), moclobemid (up to 0.3ng/l) and venlafaxine (up to 1.9ng/l) were detected. However this highlights their inadequate elimination in the drinking waste treatment facility. The presence of antidepressants in drinking water and the aquatic environment could have long-term effects even at low exposure level

Differential Risk of Peptic Ulcer Among Users of Antidepressants Combined With Nonsteroidal Anti-inflammatory Drugs.

PubMed

Shin, Ju-Young; Song, Inmyung; Lee, Jin-Ho; Yoon, Jong Lull; Kwon, Jun Soo; Park, Byung-Joo

2017-04-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to have an increased risk of gastrointestinal adverse events, and the risk may be further increased by combined use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, little has been known about the risk of peptic ulcer associated with other classes of antidepressants or individual antidepressants combined with NSAIDs. We conducted a retrospective cohort study to define the risk of peptic ulcer associated with combined use of antidepressants and NSAIDs, as compared with use of antidepressants alone. Using the Korean Health Insurance Review and Assessment Service database, we identified a total of 1,127,622 patients who began receiving antidepressants between 2009 and 2012. Propensity-based matching and Cox proportional hazards models were used to compare the risk of peptic ulcer between antidepressant users with NSAIDs and those without NSAIDs matched in a 1:1 ratio, for a total of 768,850 patients. The risk of peptic ulcer did not increase with combined use of overall antidepressants and NSAIDs, as compared with antidepressant use alone (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.99-1.06). A slightly increased risk was observed for combined use of NSAIDs with tricyclic antidepressants (HR, 1.15; 95% CI, 1.09-1.21) and with SSRIs (HR, 1.08; 95% CI, 1.01-1.16). We found that although concomitant use of NSAIDs and antidepressants was not associated with an increased risk of peptic ulcer for antidepressants in general, it was so for some specific classes including tricyclic antidepressants and SSRIs. However, we cannot rule out the possibility that the increased risk was solely due to NSAID use.

Targeting Glutamatergic Signaling for the Development of Novel Therapeutics for Mood Disorders

PubMed Central

Machado-Vieira, R.; Salvadore, G.; Ibrahim, L.; DiazGranados, N.; Zarate, C.A.

2009-01-01

There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of antidepressant action. Low rates of remission, a delay of onset of therapeutic effects, continual residual depressive symptoms, relapses, and poor quality of life are unfortunately common in patients with mood disorders. Offering alternative options is requisite in order to reduce the individual and societal burden of these diseases. The glutamatergic system is a promising area of research in mood disorders, and likely to offer new possibilities in therapeutics. There is increasing evidence that mood disorders are associated with impairments in neuroplasticity and cellular resilience, and alterations of the glutamatergic system are known to play a major role in cellular plasticity and resilience. Existing antidepressants and mood stabilizers have prominent effects on the glutamate system, and modulating glutamatergic ionotropic or metabotropic receptors results in antidepressant-like properties in animal models. Several glutamatergic modulators targeting various glutamate components are currently being studied in the treatment of mood disorders, including release inhibitors of glutamate, N-methyl-D-aspartate (NMDA) antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput enhancers, and glutamate transporter enhancers. This paper reviews the currently available knowledge regarding the role of the glutamatergic system in the etiopathogenesis of mood disorders and putative glutamate modulators. PMID:19442176

Antidepressant Use among Blacks and Whites in the United States

PubMed Central

González, Hector M.; Croghan, Thomas W.; West, Brady T.; Tarraf, Wassim; Williams, David R.; Nesse, Randolph; Taylor, Robert Joseph; Hinton, Ladson; Neighbors, Harold W.; Jackson, James S.

2008-01-01

Objective The study objective was to estimate the prevalence and correlates of antidepressant use by black and white Americans. Methods Data from the Collaborative Psychiatric Epidemiology Surveys (CPES) were analyzed to calculate nationally representative estimates of antidepressant use by black and white Americans. Setting The 48 coterminous United States was the setting. Participants Household residents ages 18 years and older (N=9,723) participated in the study. Main Outcomes The primary outcome was past-year antidepressant use (n=1,004). Results Among individuals with 12-month depressive and anxiety disorders (n=516), blacks (14.6%) had significantly lower (p < 0.001) antidepressant use than whites (32.4%). Depression severity was significantly associated with higher antidepressant use for whites, but not blacks. Psychiatric disorders and vascular disease significantly increased the odds of past-year antidepressant use. The increased prevalence of antidepressant use associated with vascular disease was independent of diagnosable psychiatric disorders. Among respondents not meeting criteria for 12-month depressive and anxiety disorders, lifetime depressive and anxiety disorders and vascular disease significantly increased the odds of antidepressant use. Conclusions Few white and fewer black Americans with depressive and anxiety disorders receive antidepressant treatment. Higher depression severity was associated with more antidepressant use for whites, but not blacks. Antidepressant use was associated with medical conditions related to vascular disease, and these medical conditions were independent of coexisting psychiatric conditions. The results also indicate that many antidepressants are used for maintenance pharmacotherapy for depressive and anxiety disorders as well as common medical conditions associated with vascular disease. PMID:18832498

Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants.

PubMed

Ogawa, Shintaro; Kunugi, Hiroshi

2015-01-01

Cannabis and analogs of Δ⁹-tetrahydrocannabinol have been used for therapeutic purposes, but their therapeutic use remains limited because of various adverse effects. Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD). Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD. Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors). In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors' therapeutic potential. MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2. In the hypothalamic-pituitary-adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted.

Phytochemistry and pharmacology of anti-depressant medicinal plants: A review.

PubMed

Martins, Jeanette; S, Brijesh

2018-05-16

Stress renders an individual to experience mental pressure and exhaustion which brings about feelings of anxiety, depression, anger and/or other negative emotions. Depression affects a person's state of mind, behaviour, health and is often associated with suicide. The use of anti-depressant drugs as therapeutic agents is associated with symptoms such as, delayed onset of action, side-effects, drug-drug and dietary interactions, sexual dysfunction, cardiac toxicity, etc. Thus, there is need to target these issues and improve current treatment options. Medicinal plants have long been used in discovering novel treatment strategies and compounds with promising roles in treating various disease conditions. There has been an increase, worldwide, in the use of medicinal plants and herbs for developing nutraceuticals for treatment of depression and other psychiatric disorders. Medicinal plants in their natural forms are valuable as they are rich in various phytochemical compounds. These phytochemical compounds have pharmacological roles in treating various diseases conditions; apart from being widely available in nature and commercially beneficial. The phytochemical compounds in plants are constantly being explored through various experimental studies to determine the molecular basis of how medicinal plants work in relation to drugs and diseases and to develop neutraceuticals for improving conditions. This review summarizes 110 medicinal plants and their phytochemical constituents that have been shown to possess anti-depressant activity. This review also highlights the various mechanisms of anti-depressant action of some of these plants and their plant parts like roots, stem, leaves, flowers, fruit or whole plant; phytochemical compounds showing anti-depressant activity such flavanoids, steroids, saponins, sugars, lectins, alkaloids, etc.; and various anti-depressant screening models used such as tail suspension test, forced swim test, chronic unpredictable stress test

Racial and ethnic disparities in antidepressant drug use.

PubMed

Chen, Jie; Rizzo, John A

2008-12-01

Little is known about racial and ethnic disparities in health care utilization, expenditures and drug choice in the antidepressant market. This study investigates factors associated with the racial and ethnic disparities in antidepressant drug use. We seek to determine the extent to which disparities reflect differences in observable population characteristics versus heterogeneity across racial and ethnic groups. Among the population characteristics, we are interested in identifying which factors are most important in accounting for racial and ethnic disparities in antidepressant drug use. Using Medical Expenditure Panel Survey (MEPS) data from 1996-2003, we have an available sample of 10,416 Caucasian, 1,089 African American and 1,539 Hispanic antidepressant drug users aged 18 to 64 years. We estimate individual out-of-pocket payments, total prescription drug expenditures, drug utilization, the probability of taking generic versus brand name antidepressants, and the share of drugs that are older types of antidepressants (e.g., TCAs and MAOIs) for these individuals during a calendar year. Blinder-Oaxaca decomposition techniques are employed to determine the extent to which disparities reflect differences in observable population characteristics versus unobserved heterogeneity across racial and ethnic groups. Caucasians have the highest antidepressant drug expenditures and utilization. African-Americans have the lowest drug expenditures and Hispanics have the lowest drug utilization. Relative to Caucasians and Hispanics, African-Americans are more likely to purchase generics and use a higher share of older drugs (e.g., TCAs and MAOIs). Differences in observable characteristics explain most of the racial/ethnic differences in these outcomes, with the exception of drug utilization. Differences in health insurance and education levels are particularly important factors in explaining disparities. In contrast, differences in drug utilization largely reflect unobserved

The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants

PubMed Central

Baumann, Pierre; Ulrich, Sven; Eckermann, Gabriel; Gerlach, Manfred; Kuss, Hans-Joachim; Laux, Gerd; Müller-Oerlinghausen, Bruno; Rao, Marie Luise; Riederer, Peter; Zernig, Gerald; Hiemke, Christoph

2005-01-01

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration–clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM, Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment. TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These

Modern molecular study of weight gain related to antidepressant treatment: clinical implications of the pharmacogenetic testing.

PubMed

Ageu, Luminiţa Ştefania; Levai, Codrina Mihaela; Andreescu, Nicoleta Ioana; Grigoraş, Mirela Loredana; Hogea, Lavinia Maria; Chiriac, Daniela Veronica; Folescu, Roxana; Bredicean, Ana Cristina; Nussbaum, Liliana Maria; Enătescu, Virgil Radu; Poroch, Vladimir; Lupu, Viorel; Puiu, Maria; Nussbaum, Laura Alexandra

2018-01-01

Antidepressant medication influences cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of antidepressants in children and adolescents, their metabolic and endocrine adverse effects are of particular concern, especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on antidepressant's adverse effects include CYP [cytochrome P450 (CYP450)] polymorphisms. We target to evaluate the efficacy of the pharmacogenetic testing, when prescribing antidepressants, in correlation with the occurrence of adverse events and weight gain. Our research was performed between the years 2010 and 2016, in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania. We recruited 80 patients, children and adolescents with depressive disorders. Our study sample was divided in two groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 - 40 patients without pharmacogenetic testing before the treatment election. Our results show statistically significant differences concerning the weight gain for groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic testing). The CYP genotype and the pharmacogenetic testing, for choosing the personalized antidepressant therapy in children and adolescents with depressive disorders, proved to be good predictors for the response to antidepressants and the side effects registered, especially for weight gain. The significant correlations between the CYP polymorphisms for group G2 (without pharmacogenetic testing) and the weight gain/body mass index (BMI) increase, as major side effects induced by antidepressants, proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk pediatric categories.

Depression, Antidepressants, and Falls Among Community-Dwelling Elderly People: The MOBILIZE Boston Study

PubMed Central

2013-01-01

Background. The mechanisms linking falls and depression are still unknown. The aim of the study is to examine the association between depression and antidepressants, with indoor and outdoor falls, and to investigate how antidepressants mediate this relationship. Methods. The study included 763 men and women aged 70 and older with baseline measures for depression and antidepressant use are captured with prospective data on falls from the “Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly” (MOBILIZE) Boston study, which is a population-based longitudinal study (from 2005 to 2009). Results. Overall, the rate of falls was 26 falls/100 person-years. Seventeen percent of participants had clinically significant depressive symptoms (CSDS), and 12% used antidepressants. CSDS increased the risk of indoor and outdoor falls (incidence rate ratio [IRR] = 1.6, 95% confidence interval [CI] = 1.2–2.3, p < .01; IRR = 1.6, 95% CI = 1.2–2.2, p < .01). Antidepressant use increased the risk of outdoor falls by 70% and partially mediated the association between CSDS and outdoor falls (IRR = 1.7, 95% CI = 1.2–2.5, p < .05). There was no relationship between antidepressant use and indoor falls. Similar results were observed when depression was considered as a continuous variable. Conclusions. Depression increased the risk of indoor and outdoor falls. Antidepressant use among older adults with CSDS increased the risk of outdoor, but not indoor falls. Clinicians should carefully consider the role of antidepressants among older adults with CSDS and their potential increase for the risk of outdoor falls. PMID:23817088

Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy

PubMed Central

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

2015-01-01

The biochemical targets for antidepressants are relatively well established, but we lack a clear understanding of how actions at these proteins translate to clinical benefits. This study used a novel rodent assay to investigate how different antidepressant drugs act to modify affective biases that have been implicated in depression. In this bowl-digging task, rats encounter two equal value learning experiences on separate days (one during an affective manipulation and the other during control conditions). This induces an affective bias that is quantified using a preference test in which both digging substrates are presented together and the individual rats’ choices recorded. The assay can be used to measure affective biases associated with learning (when the treatment is given at the time of the experience) or examine the modification of previously acquired biases (when the treatment is administered before the preference test). The rapid-onset antidepressant ketamine, but not the delayed-onset antidepressant, venlafaxine, attenuated the previously acquired FG7142-induced negative bias following systemic administration. Venlafaxine but not ketamine induced a positive bias when administered before learning. We then used local drug infusions and excitotoxic lesions to localize the effects of ketamine to the medial prefrontal cortex and venlafaxine to the amygdala. Using a modified protocol we also showed that positive and negative biases amplified further when the numbers of substrate–reinforcer associations are increased. We propose that this pattern of results could explain the delayed onset of action of venlafaxine and the rapid onset of action but lack of long-term efficacy seen with ketamine. PMID:25740288

Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain.

PubMed

Tyeryar, Kimberly R; Vongtau, Habiba O U; Undieh, Ashiwel S

2008-01-24

Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we have examined the antidepressant-induced production of CDP-diacylglycerol which is both a product of diacylglycerol phosphorylation and a precursor for the synthesis of physiologically critical glycerophospholipids such as the phosphatidylinositides. For this, drug effects on [3H]cytidine-labeled CDP-diacylglycerol and [3H]inositol-labeled phosphatidylinositides were measured in response to the tricyclics desipramine and imipramine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, the atypical antidepressants maprotiline and nomifensine, and several monoamine oxidase inhibitors. Multiple compounds from each antidepressant category significantly stimulated [3H]CDP-diacylglycerol accumulation in cerebrocortical, hippocampal, and striatal tissues, and also enhanced the resynthesis of inositol phospholipids. Conversely, various antipsychotics, anxiolytics, and non-antidepressant psychotropic agents failed to significantly induce CDP-diacylglycerol or phosphoinositide synthesis. Drug-induced CDP-diacylglycerol accumulation was independent of lithium and only partially dependent on phosphoinositide hydrolysis, thus indicating that antidepressants can mobilize CDP-diacylglycerol from additional

Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain

PubMed Central

Tyeryar, Kimberly R; Vongtau, Habiba OU; Undieh, Ashiwel S

2008-01-01

Background Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we have examined the antidepressant-induced production of CDP-diacylglycerol which is both a product of diacylglycerol phosphorylation and a precursor for the synthesis of physiologically critical glycerophospholipids such as the phosphatidylinositides. For this, drug effects on [3H]cytidine-labeled CDP-diacylglycerol and [3H]inositol-labeled phosphatidylinositides were measured in response to the tricyclics desipramine and imipramine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, the atypical antidepressants maprotiline and nomifensine, and several monoamine oxidase inhibitors. Results Multiple compounds from each antidepressant category significantly stimulated [3H]CDP-diacylglycerol accumulation in cerebrocortical, hippocampal, and striatal tissues, and also enhanced the resynthesis of inositol phospholipids. Conversely, various antipsychotics, anxiolytics, and non-antidepressant psychotropic agents failed to significantly induce CDP-diacylglycerol or phosphoinositide synthesis. Drug-induced CDP-diacylglycerol accumulation was independent of lithium and only partially dependent on phosphoinositide hydrolysis, thus indicating that antidepressants can mobilize CDP

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy.

PubMed

Bechtholt-Gompf, Anita J; Smith, Karen L; John, Catherine S; Kang, Hannah H; Carlezon, William A; Cohen, Bruce M; Ongür, Dost

2011-06-01

In patients, ketamine is a fast-acting antidepressant that can induce long-lasting symptom relief. Similar rapid effects have been reported in rodents, but reports of lasting effects are limited. We sought to extend past findings by examining dose-response curves that overlap with the individual doses previously reported to induce lasting effects in rodents and determining whether effects generalize to the tail suspension test (TST) and Balb/cJ mice. Using common tests of antidepressant efficacy we first confirmed our ability to detect the effects of desipramine, a well-characterized antidepressant drug. Next, we sought to determine whether two non-competitive NMDA antagonists, ketamine and MK-801, had long-lasting antidepressant-like effects in CD-1 mice, a strain that has often been used to demonstrate the short-term antidepressant-like effects of ketamine. Finally, we examined the short- and long-term effects of ketamine in a mouse strain that is more sensitive to antidepressant-like effects, Balb/cJ mice. In CD-1 mice, desipramine treatment yielded significant short-term antidepressant-like effects in the TST and the forced swimming test (FST). However, no significant enduring effects of ketamine or MK-801 were observed 1 week later. Short-term effects of ketamine in the TST were observed in Balb/cJ mice, but lasting effects were absent 1 week later. Although the TST and FST have been widely used to detect antidepressant-like effects in mice, they do not appear to be sensitive to long-lasting antidepressant-like effects of ketamine in mice and, therefore, do not model the therapeutic effects of ketamine that have been reported in humans with major depression.

Antidepressants: Selecting One That's Right for You

MedlinePlus

... unless you've tried other antidepressants first without improvement. Monoamine oxidase inhibitors (MAOIs). MAOIs — such as tranylcypromine ( ... selected an antidepressant, you may start to see improvement in a few weeks, but it may take ...

Antidepressant Medication Management among Older Patients Receiving Home Health Care

PubMed Central

Bao, Yuhua; Shao, Huibo; Bruce, Martha L.; Press, Matthew J.

2014-01-01

Objective Antidepressant management for older patients receiving home health care (HHC) may occur through two pathways: nurse-physician collaboration (without patient visits to the physician) and physician management through office visits. This study examines the relative contribution of the two pathways and how they interplay. Methods Retrospective analysis was conducted using Medicare claims of 7,389 depressed patients 65 or older who received HHC in 2006–7 and who possessed antidepressants at the start of HHC. A change in antidepressant therapy (vs. discontinuation or refill) was the main study outcome and could take the form of a change in dose, switch to a different antidepressant, or augmentation (addition of a new antidepressant). Logistic regressions were estimated to examine how use of home health nursing care, patient visits to physicians, and their interactions predict a change in antidepressant therapy. Results About 30% of patients experienced a change in antidepressants versus 51% who refilled and 18% who discontinued. Receipt of mental health specialty care was associated with a statistically significant, 10–20 percentage-point increase in the probability of antidepressant change; receipt of primary care was associated with a small and statistically significant increase in the probability of antidepressant change among patients with no mental health specialty care and above-average utilization of nursing care. Increased home health nursing care in absence of physician visits was not associated with increased antidepressant change. Conclusions Active antidepressant management resulting in a change in medication occurred on a limited scale among older patients receiving HHC. Addressing knowledge and practice gaps in antidepressant management by primary care providers and home health nurses and improving nurse-physician collaboration will be promising areas for future interventions. PMID:25158915

Antidepressant use and mortality in very old people.

PubMed

Boström, Gustaf; Hörnsten, Carl; Brännström, Jon; Conradsson, Mia; Nordström, Peter; Allard, Per; Gustafson, Yngve; Littbrand, Håkan

2016-07-01

Antidepressant treatment may increase the risk of death. The association between antidepressants and mortality has been evaluated in community-dwelling older people, but not in representative samples of very old people, among whom dementia, multimorbidity, and disability are common. Umeå 85+/GERDA study participants (n = 992) aged 85, 90, and ≥95 years were followed for up to five years. Cox proportional hazard regression models were used to analyze mortality risk associated with baseline antidepressant treatment, adjusted for potential confounders. Mean age was 89 years; 27% of participants had dementia, 20% had stroke histories, 29% had heart failure, and 16% used antidepressants. In age- and sex-adjusted analyses, antidepressant use was associated with a 76% increased mortality risk (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.41-2.19). Adding adjustment for Geriatric Depression Scale score, HR was 1.62 (95% CI, 1.29-2.03). The association was not significant when adjusting for additional confounding factors (HR = 1.08; 95% CI, 0.85-1.38). Interaction analyses in the fully adjusted model revealed a significant interaction between sex and antidepressant use (HR: 1.76; 95% CI, 1.05-2.94). Among male and female antidepressant users, the HRs for death were 0.76 (95% CI, 0.47-1.24) and 1.28 (95% CI, 0.97-1.70), respectively. Among very old people, baseline antidepressant treatment does not seem to be independently associated with increased mortality risk. However, the risk may be different in men and women. This difference and the potential risk of initial treatment require further investigation in future cohort studies of very old people.

The role of antidepressants in the management of inflammatory bowel disease (IBD): a short report on a clinical case-note audit.

PubMed

Mikocka-Walus, Antonina A; Gordon, Andrea L; Stewart, Benjamin J; Andrews, Jane M

2012-02-01

This study sought to determine the frequency of use and types of antidepressants used in IBD patients and to collect data with respect to any effect of antidepressants on the course of IBD in a usual care setting. A case-note audit was conducted at an IBD Service in a public tertiary hospital. Included patients were those diagnosed with IBD by a gastroenterologist; and have had contact with the IBD Service in the last 6months. Descriptive statistics were used to summarise the data. Overall, 313 patients were eligible and 287 had complete data. Overall, 51 (17.8%) patients were currently taking antidepressants and 71 (24.7%) previously received antidepressants. Eighty-three (28.9%) patients had used an antidepressant at some time. In terms of disease activity while on antidepressants, the majority of patients had inactive disease but presented with what were thought by their clinicians to be functional symptoms. Antidepressants are commonly prescribed in IBD patients. In our cohort, they appear to be mostly used for functional symptoms. The current data do not allow us to judge whether they improve IBD disease activity. Targeted studies are needed to answer this question and to improve practice and patient outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

[Perioperative adverse events related to antidepressive agents use].

PubMed

Rozec, B; Cinotti, R; Blanloeil, Y

2011-11-01

Depression is the most common psychiatric disease, which is treated by the use of antidepressive agents possessing various mechanisms of action. Thus, the use in preoperative period of antidepressive agents is frequent (7% of patients scheduled for surgery). The objective of this review was to update the knowledge on the drug interactions between antidepressive agents and drugs used in perioperative period. (i) Medline and Ovid databases using combination of antidepressive agent and perioperative period as keywords; (ii) national and European epidemiologic database; (iii) expert recommendation and official French health agency; (iv) reference book chapters. The clinical practice showed a limited risk of adverse event related to antidepressant agents interaction with perioperative used drugs. In the two past decades, few relevant observations of adverse event related with imipramine and monoamine oxidase inhibitors use was reported. The most recent antidepressive agents had no serious adverse interaction. Nevertheless, the serotonin syndrome has to be known as far as it is more and more reported. In case of hypotension, the use of vasopressive agent has to be careful because of excessive response. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Long Noncoding RNA-Associated Transcriptomic Changes in Resiliency or Susceptibility to Depression and Response to Antidepressant Treatment

PubMed Central

Roy, Bhaskar; Wang, Qingzhong; Dwivedi, Yogesh

2018-01-01

Abstract Background Recent emergence of long noncoding RNAs in regulating gene expression and thereby modulating physiological functions in brain has manifested their possible role in psychiatric disorders. In this study, the roles of long noncoding RNAs in susceptibility and resiliency to develop stress-induced depression and their response to antidepressant treatment were examined. Methods Microarray-based transcriptome-wide changes in long noncoding RNAs were determined in hippocampus of male Holtzman rats who showed susceptibility (learned helplessness) or resiliency (nonlearned helplessness) to develop depression. Changes in long noncoding RNA expression were also ascertained after subchronic administration of fluoxetine to learned helplessness rats. Bioinformatic and target prediction analyses (cis- and trans-acting) and qPCR-based assays were performed to decipher the functional role of altered long noncoding RNAs. Results Group-wise comparison showed an overrepresented class of long noncoding RNAs that were uniquely associated with nonlearned helplessness or learned helplessness behavior. Chromosomal mapping within the 5-kbp flank region of the top 20 dysregulated long noncoding RNAs in the learned helplessness group showed several target genes that were regulated through cis- or trans-actions, including Zbtb20 and Zfp385b from zinc finger binding protein family. Genomic context of differentially expressed long noncoding RNAs showed an overall blunted response in the learned helplessness group regardless of the long noncoding RNA classes analyzed. Gene ontology exhibited the functional clustering for anatomical structure development, cellular architecture modulation, protein metabolism, and cellular communications. Fluoxetine treatment reversed learned helplessness-induced changes in many long noncoding RNAs and target genes. Conclusions The involvement of specific classes of long noncoding RNAs with distinctive roles in modulating target gene expression

Antidepressant pharmacotherapy in old-age depression-a review and clinical approach.

PubMed

Pruckner, Nathalie; Holthoff-Detto, Vjera

2017-06-01

Depression in old age is a disabling disease associated with functional and cognitive decline severely affecting quality of life. Studies specifically investigating antidepressant treatment for this special cohort of patients remain scarce and results are often conflicting. A narrative literature review was undertaken, synthesizing findings from published studies, systematic reviews, and treatment guidelines specifically conducted in elderly depressed patients to summarize implications and current recommendations as well as gaps in evidence for old-age pharmacologic treatment. PubMed and Medline databases were searched for articles from July 2011 to July 2016. Only RCTs, meta-analyses, systematic reviews, and treatment guidelines focussing on the effect of antidepressant pharmacotherapy in old-aged participants were extracted, analysed, and discussed. The search resulted in a total of 26 articles. Selective serotonin reuptake inhibitors (SSRIs) and other second-generation antidepressants are recommended for first-line treatment of old-age depression. The differences in efficacy and tolerability within different substances and substance classes are minimal or non-existent. Tricyclic antidepressants (TCAs) are only considered for second-line treatment, due to their cardiac risk profile and anticholinergic effects. In treatment-resistant depression, augmentation therapy options include lithium and atypical antipsychotics. There is convincing evidence that antidepressants are efficacious in the treatment of old-age depression and that rationales are necessary for treatment planning. However, evidence-based data on recovery and remission rates in old-age depression specific to certain antidepressant drugs are still missing in trials and are of great importance for pharmacological treatment of old-age depression in daily clinical practice.

Antidepressant Use and Incident Urinary Incontinence: A Literature Review.

PubMed

Dane, Kathryn E; Gatewood, Sharon B S; Peron, Emily P

2016-03-01

To review available data examining antidepressant use and incident urinary incontinence (UI). PubMed was used to conduct the literature search for this review. In the primary search, the term "antidepressive agents" was searched as a medical subject heading, a pharmacological action, and a keyword phrase. This choice was made so that any relevant articles would include complete results for antidepressive agents. "Antidepressive agents" was combined with the key phrase "drug-induced urinary incontinence" to complete this primary search. Relevant articles published in English and examining human subjects were included. The study authors determined appropriateness of articles for inclusion, focusing on those examining antidepressant-associated UI. This literature review identified three cohort studies and 11 case reports examining various associations between antidepressant use and incident UI. All 11 case reports and 1 cohort study reviewed suggest an association between antidepressant use and incident UI. It remains unclear which drugs are most problematic and which patients are at greatest risk, and more data are needed to confirm an association, especially in older adults. Comprehensive medication reviews should be employed by pharmacists to identify potential medication-related causes of UI.

Escitalopram versus other antidepressive agents for depression.

PubMed

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

2009-04-15

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. 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. Electronic databases were searched up to July 2008. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. 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 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. 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 0.53, 95% CI 0.30 to 0.93). Significantly fewer patients allocated to escitalopram withdrew from

Prenatal Antidepressants and Autism Spectrum Disorder

DTIC Science & Technology

2014-09-01

citalopram, fluoxetine, bupropion, valproic acid, autism spectrum disorder, developmental disorders, prenatal effects, neurodevelopment , rat, behavior...1 AWARD NUMBER: W81XWH-13-1-0306 TITLE: Prenatal Antidepressants and Autism Spectrum Disorder PRINCIPAL INVESTIGATOR...TYPE Annual 3. DATES COVERED 1Sept 2013-31Aug2014 4. TITLE AND SUBTITLE Prenatal Antidepressants and Autism Spectrum Disorder 5a

Association of cerebrovascular events with antidepressant use: a case-crossover study.

PubMed

Wu, Chi-Shin; Wang, Sheng-Chang; Cheng, Yu-Cheng; Gau, Susan Shur-Fen

2011-05-01

The authors sought to assess the risk of cerebrovascular events associated with use of antidepressant medications. The authors conducted a case-crossover study of 24,214 patients with stroke enrolled in the National Health Insurance Research Database in Taiwan from 1998 to 2007. The authors compared the rates of antidepressant use during case and control time windows of 7, 14, and 28 days. Adjustments were made for time-dependent variables, such as health system utilization and proposed confounding medications. Stratified analyses were performed for valuing the interaction between the stroke risk of antidepressant use and age, sex, presence of mood disorder, stroke type, severity of chronic illness, and duration of antidepressant treatment. A conditional logistic regression model was used to determine the odds of antidepressant use during case time windows. The adjusted odds ratio of stroke risk with antidepressant exposure was 1.48 (95% confidence interval=1.37-1.59) using 14-day time windows. Stroke risk was negatively associated with the number of antidepressant prescriptions reported. Use of antidepressants with high inhibition of the serotonin transporter was associated with a greater risk of stroke than use of other types of antidepressants. These findings suggest that antidepressant use may be associated with an increased risk of stroke. However, the underlying mechanisms remain unclear.

Antidepressant drugs can modify cytotoxic action of temozolomide.

PubMed

Bielecka, A M; Obuchowicz, E

2017-09-01

Cancer patients often require antidepressant treatment due to comorbid depressive disorder. However, recent studies have demonstrated that antidepressant drugs affect the efficacy of chemotherapy and promote progression of cancer. Apart from the main mood-improving effect, antidepressant drugs also produce analgesic, anxiolytic, hypnotic and pro-cognitive actions. Patients suffering from brain cancer constitute the greatest percentage of depressive cancer patients. However, vital safety and efficacy issues related to combined therapy with temozolomide, the first-line cytostatic in patients diagnosed with glioblastoma multiforme, and antidepressant drugs have yet to be addressed. The aim of the present studies was to evaluate the effect of three antidepressant drugs (imipramine, fluoxetine and tranylcypromine) on the cytotoxic efficacy of temozolomide on T98G cells, a human glioblastoma cell line. In our experiments, we used a complex experimental in vitro system to mimic the instability of a tumour's oxygen supply, thereby reproducing conditions that occur inside the tumour. The effect of the interaction between temozolomide and antidepressant drugs on viability, apoptosis and intensity of divisions of glioblastoma cells was evaluated under different oxygen conditions. The results of our studies demonstrated that imipramine and tranylcypromine reduced the cytotoxic efficacy of temozolomide under some oxygen conditions while fluoxetine did not demonstrate such effects. © 2016 John Wiley & Sons Ltd.

Antidepressant Activity of Brahmi in Albino Mice

PubMed Central

Kadali, SLDV Ramana Murty; M.C., Das; Rao A.S.R., Srinivasa; Sri G, Karuna

2014-01-01

Context: In traditional system of medicine brahmi has been used to enhance memory. Recently it has been reported to have action in psychiatric disorders. With these backgrounds the work has been undertaken to study antidepressant activity of brahmi in albino mice. Aim: To evaluate antidepressant activity of brahmi in experimental models. Materials and Methods: The antidepressant activity was studied in albino mice using forced swimming test (FST), tail suspension test (TST) and shock induced depression (SID). Imipramine (10mg/kg), fluoxetine (30mg/kg) were used as standard drugs and brahmi (10, 20, 30mg/kg) was used as test drug. Results: Brahmi exhibited significant decrease in duration of immobility in FST and reduced the shock induced decrease in activity in SID models. It didn’t show any activity in the TST model. Conclusion: Brahmi has shown antidepressant activity in FST and SID. PMID:24783074

[Prevalence of Avoidable Potential Interactions Between Antidepressants and Other Drugs in Colombian Patients].

PubMed

Machado-Alba, Jorge E; Morales-Plaza, Cristhian David

2013-06-01

To determine the possible drugs interactions with antidepressive agents in data bases of patients in the Health Insurance System of Colombia. From data bases of about 4 million users in Colombia, a systematic review of drugs dispensation statistics was made to identify drug interactions between antidepressive agents, cholinergic antagonists and tramadol in 2010. We identified 114,465 monthly users of antidepressive agents. Of these, 5776 (5.0%) received two, and 178 (0.2%) received three antidepressive agents simultaneously. The most frequent combination was fluoxetine+trazodone (n=3235; 56.9% of cases). About 1127 (1.0%) patients were prescribed a cholinergic antagonist simultaneously; 2523 (2.1%) users were dispensed tramadol at the same time, while raising the risk of serotonin syndrome. Drug interactions represent a potential risk that is often underestimated by physicians. Pharmacovigilance is a useful tool to optimize resources and prevent negative outcomes associated with medication. It is recommended that systematic search is made to enhance surveillance programs for the rational use of medicines in this country. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Reversal of hippocampal neuronal maturation by serotonergic antidepressants

PubMed Central

Kobayashi, Katsunori; Ikeda, Yumiko; Sakai, Atsushi; Yamasaki, Nobuyuki; Haneda, Eisuke; Miyakawa, Tsuyoshi; Suzuki, Hidenori

2010-01-01

Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, and increasing evidence suggests potential use of these drugs beyond current antidepressant therapeutics. Facilitation of adult neurogenesis in the hippocampal dentate gyrus has been suggested to be a candidate mechanism of action of antidepressant drugs, but this mechanism may be only one of the broad effects of antidepressants. Here we show a distinct unique action of the serotonergic antidepressant fluoxetine in transforming the phenotype of mature dentate granule cells. Chronic treatments of adult mice with fluoxetine strongly reduced expression of the mature granule cell marker calbindin. The fluoxetine treatment induced active somatic membrane properties resembling immature granule cells and markedly reduced synaptic facilitation that characterizes the mature dentate-to-CA3 signal transmission. These changes cannot be explained simply by an increase in newly generated immature neurons, but best characterized as “dematuration” of mature granule cells. This granule cell dematuration developed along with increases in the efficacy of serotonin in 5-HT4 receptor-dependent neuromodulation and was attenuated in mice lacking the 5-HT4 receptor. Our results suggest that serotonergic antidepressants can reverse the established state of neuronal maturation in the adult hippocampus, and up-regulation of 5-HT4 receptor-mediated signaling may play a critical role in this distinct action of antidepressants. Such reversal of neuronal maturation could affect proper functioning of the mature hippocampal circuit, but may also cause some beneficial effects by reinstating neuronal functions that are lost during development. PMID:20404165

Open questions in current models of antidepressant action

PubMed Central

Tanti, A; Belzung, C

2010-01-01

Research on depression and antidepressant drugs is necessary, as many patients display poor response to therapy. Different symptomatic and pathophysiological features have been proposed as end points of the depressive phenotype and of the antidepressant action, including anhedonia, depressed mood, alterations in morphology and activity of some brain areas (amygdala, nucleus accumbens, hippocampus, prefrontal cortex and cingulate cortex), modifications in the connectivity between brain structures, changes in neurotransmitters (serotonin, noradrenaline, glutamate and neuropeptides), brain plasticity (neurogenesis, neurotrophins) and abnormal function of the hypothalamic-pituitary adrenal axis. However, few models have been proposed to describe how these end points could induce the depressive phenotype and are involved in the mechanism of action of antidepressants. Here we propose a connectionist-inspired network of depression and antidepressant action, in which the different aetiological factors participating in the release of a depressive episode are represented by input nodes, the different symptomatic as well as pathophysiological end points are represented by an intermediate layer, and the onset of depression or of comorbid disease is represented by the output node. The occurrence of depression and the mechanism of the antidepressant action thus depend upon the weight of the interactions between the different end points, none of them being per se crucial to the onset of a depressive phenotype or to the antidepressant action. This model is heuristic to draw future lines of research concerning new antidepressant therapies, designing new animal models of depression and for a better understanding of the depressive pathology and of its comorbid pathology such as anxiety disorders. PMID:20132212

Antidepressants for depressive disorder in children and adolescents: a database of randomised controlled trials.

PubMed

Zhang, Yuqing; Zhou, Xinyu; Pu, Juncai; Zhang, Hanping; Yang, Lining; Liu, Lanxiang; Zhou, Chanjuan; Yuan, Shuai; Jiang, Xiaofeng; Xie, Peng

2018-05-31

In recent years, whether, when and how to use antidepressants to treat depressive disorder in children and adolescents has been hotly debated. Relevant evidence on this topic has increased rapidly. In this paper, we present the construction and content of a database of randomised controlled trials of antidepressants to treat depressive disorder in children and adolescents. This database can be freely accessed via our website and will be regularly updated. Major bibliographic databases (PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO and LiLACS), international trial registers and regulatory agencies' websites were systematically searched for published and unpublished studies up to April 30, 2017. We included randomised controlled trials in which the efficacy or tolerability of any oral antidepressant was compared with that of a control group or any other treatment. In total, 7377 citations from bibliographical databases and 3289 from international trial registers and regulatory agencies' websites were identified. Of these, 53 trials were eligible for inclusion in the final database. Selected data were extracted from each study, including characteristics of the participants (the study population, setting, diagnostic criteria, type of depression, age, sex, and comorbidity), characteristics of the treatment conditions (the treatment conditions, general information, and detail of pharmacotherapy and psychotherapy) and study characteristics (the sponsor, country, number of sites, blinding method, sample size, treatment duration, depression scales, other scales, and primary outcome measure used, and side-effect monitoring method). Moreover, the risk of bias for each trial were assessed. This database provides information on nearly all randomised controlled trials of antidepressants in children and adolescents. By using this database, researchers can improve research efficiency, avoid inadvertent errors and easily focus on the targeted subgroups in

Use of antidepressant medications in relation to the incidence of breast cancer

PubMed Central

Fulton-Kehoe, D; Rossing, M A; Rutter, C; Mandelson, M T; Weiss, N S

2006-01-01

Although associations have been reported between antidepressant use and risk of breast cancer, the findings have been inconsistent. We conducted a population-based case–control study among women enrolled in Group Health Cooperative (GHC), a health maintenance organization in Washington State. Women with a first primary breast cancer diagnosed between 1990 and 2001 were identified (N=2904) and five controls were selected for each case (N=14396). Information on antidepressant use was ascertained through the GHC pharmacy database and on breast cancer risk factors and screening mammograms from GHC records. Prior to one year before diagnosis of breast cancer, about 20% of cases and controls had used tricyclic antidepressants (adjusted odds ratio=1.06, 95% CI 0.94–1.19) and 6% of each group had used selective serotonin reuptake inhibitors (OR=0.98, 95% CI 0.80–1.18). There also were no differences between cases and controls with regard to the number of prescriptions filled or the timing of use. Taken as a whole, the results from this and other studies to date do not indicate an altered risk of breast cancer associated with the use of antidepressants overall, by class, or for individual antidepressants. PMID:16523201

[Antidepressant drugs and breastfeeding].

PubMed

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

2007-01-01

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

Treatment decisions on antidepressants in nursing homes: a qualitative study.

PubMed

Iden, Kristina Riis; Hjørleifsson, Stefan; Ruths, Sabine

2011-12-01

To explore decision-making on treatment with antidepressants among doctors and nurses in nursing homes. A qualitative study based on interviews with three focus groups comprising eight physicians engaged full time, eight physicians engaged part time, and eight registered nurses, respectively. The interview guide comprised questions on initiating, evaluating, and withdrawing treatment with antidepressants. The interviews were audio-recorded, transcribed, and analysed by systematic text condensation. The first theme was the diagnostic process. The informants expressed difficulty in differentiating between depression and sorrow resulting from loss in old age. Further, the doctors reported that they relied on nurses' observations and rarely carried out systematic diagnostic work and follow-up of patients with depression. The second theme was treatment. Antidepressants were usually the only type of treatment provided, and patients were kept on medication even though staff felt uncertain whether this was effective. The third theme was who really determines the treatment. Registered nurses reported that unskilled and auxiliary nursing staff requested drug treatment, and doctors felt some pressure from the nurses to prescribe antidepressants. This study suggests that the quality of diagnosis and treatment for depression in nursing homes needs to be improved in Norway. Doctors should be more available and take responsibility and leadership in medical decisions.

Cost sharing and branded antidepressant initiation among patients treated with generics.

PubMed

Buxbaum, Jason D; Chernew, Michael E; Bonafede, Machaon; Vlahiotis, Anna; Walter, Deborah; Mucha, Lisa; Fendrick, A Mark

2018-04-01

To determine the relationship between consumer cost sharing for branded antidepressants and the initiation of branded therapy among patients with major depressive disorder (MDD) filling a prescription for generic MDD medication.  Retrospective cross-sectional analyses. Patients aged 18 to 64 years with MDD who filled a generic antidepressant were identified in commercial claims data for 2012 to 2014. For each year-specific analysis, an average cost-sharing index for branded antidepressants at the level of the plan was computed. Multivariable models were used to estimate the relationship between plan-level cost sharing for branded antidepressant medications and the filling of branded prescriptions, with demographic and clinical variables as covariates. For patients with MDD filling a generic prescription, increases in branded cost sharing were associated with significant decreases in the likelihood of filling a branded antidepressant in each year (P <.001). Results in 2012 imply that a shift from the 0th to 90th percentile in the branded cost-sharing index corresponded with a 9.5% decrease in the relative likelihood of a branded fill among patients receiving a generic antidepressant. The corresponding figures for 2013 and 2014 were 9.3% and 3.5%, respectively. In MDD, patients and clinicians who dutifully adhere to guidelines requiring a trial of first-line medication may ultimately require therapy with alternate agents to achieve adequate disease control. A "reward the good soldier" benefit design would lower cost sharing for higher-tier evidence-based therapies when clinically indicated. Results suggest that narrowing the gap in cost sharing between branded and generic medications following a trial of a generic agent might improve access to second-line treatment in MDD.

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

Antidepressant use and cognitive decline in community-dwelling elderly people - The Three-City Cohort.

PubMed

Carrière, Isabelle; Norton, Joanna; Farré, Amandine; Wyart, Marilyn; Tzourio, Christophe; Noize, Pernelle; Pérès, Karine; Fourrier-Réglat, Annie; Ritchie, Karen; Ancelin, Marie Laure

2017-04-19

Cognitive impairment is very common in late-life depression, principally affecting executive skills and information processing speed. The aim of the study was to examine the effect of antidepressant treatment on cognitive performances over a 10-year period. The community-based cohort included 7381 participants aged 65 years and above. Five cognitive domains (verbal fluency, psychomotor speed, executive function, visuospatial skills and global cognition) were assessed up to five times over 10 years of follow-up. Treatment groups included participants under a specific antidepressant class at both baseline and the first follow-up and their follow-up cognitive data were considered until the last consecutive follow-up with a report of antidepressant use of the same class. Linear mixed models were used to compare baseline cognitive performance and cognitive decline over time according to antidepressant treatment. The models were adjusted for multiple confounders including residual depressive symptoms assessed by the Center for Epidemiologic Studies-Depression scale. At baseline, 4.0% of participants were taking antidepressants. Compared to non-users, tricyclic antidepressant users had lower baseline performances in verbal fluency, visual memory and psychomotor speed, and selective serotonin reuptake inhibitor users in verbal fluency and psychomotor speed. For the two other cognitive abilities, executive function and global cognition, no significant differences were found at baseline irrespective of the antidepressant class. Regarding changes over time, no significant differences were observed in comparison with non-users whatever the cognitive domain, except for a slight additional improvement over the follow-up in verbal fluency skills for tricyclic antidepressant users. In this large elderly general population cohort, we found no evidence for an association between antidepressant use and post-treatment cognitive decline over 10 years of follow-up in various

The cost of antidepressant overdose.

PubMed

D'Mello, D A; Finkbeiner, D S; Kocher, K N

1995-11-01

Ninety percent of suicide attempts referred to a general hospital are by self-poisoning. Among women, drug overdose is the commonest means of suicide. In a retrospective naturalistic review of 200 patients who were treated in the Critical Care Unit of a general hospital following medication overdose, 12% were antidepressant overdoses. The mean duration of hospital stay for overdose with tricyclic antidepressants (TCA) was more than double that for overdose with selective serotonin reuptake inhibitors (SSRI) (7 vs 3 days; z = 2.20, p < 0.05). The dollar cost of hospital treatment for patients who overdosed on TCAs was four times greater than that for patients who overdosed on SSRIs ($22,923 vs $5,379; z = 2.30, p < 0.05). The tricyclic compounds clearly have a price advantage over more recently introduced antidepressant agents fluoxetine, sertraline, paroxetine, venlafaxine, and bupropion. The apparent cost advantage of prescribing a less expensive drug may be nullified by the cost associated with adverse consequences.

[Antidepressive agents and suicidal tendencies].

PubMed

Gründer, G; Veselinović, T; Paulzen, M

2014-09-01

In the last 2 years the discussions on the question whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) can lead to suicidality, aggression and violence, flared up again. The available data on the problem, which has been discussed since the introduction of this substance group in the late 1980s, is presented in this article. A systematic literature search showed that a scientific consensus exists that the benefits of antidepressant pharmacotherapy in general, and of treatment with SSRIs and selective serotonin/norepinephrine reuptake inhibitors (SSNRIs) in particular, outweigh the risks of their use. This also applies to the treatment of children, adolescents and young adults. The agitation occasionally occurring at the beginning of treatment, which can be experienced as aversive in susceptible patients, can intensify or even trigger suicidal thoughts or impulses. This has to be paid particular attention to especially at the beginning of treatment. It is recommended that the indications for antidepressant pharmacotherapy of children, adolescents and young adults are assessed by a specialist.

Antidepressant treatment outcomes of psychogenic movement disorder.

PubMed

Voon, Valerie; Lang, Anthony E

2005-12-01

Psychogenic movement disorder (PMD) is a subtype of conversion disorder. We describe the outcomes of a series of PMD patients following antidepressant treatment. Twenty-three outpatients with chronic PMD, diagnosed using Fahn and Williams' criteria, underwent psychiatric assessment. The patients were referred for assessment and management from January 2003 to July 2004. Fifteen agreed to be treated with antidepressants. Patients received citalopram or paroxetine; those who did not respond after 4 weeks of taking an optimal dose were switched to venlafaxine. Concurrently, 3 had supportive psychotherapy, and 1 had family intervention. Assessments included the DSM-IV-based Mini-International Neuropsychiatric Interview and scales measuring depression, anxiety, and motor and global severity. Eighteen patients (78%) had at least 1 Axis I diagnosis in addition to the somatoform diagnosis, and 3 (13%) had somatization disorder. Five (22%) had previous psychiatric contact. Nine (39%) had previously been treated with antidepressants, but only 4 (17%) had adequate trials. No significant differences existed in patient characteristics between treated and untreated groups. Among treated patients, Montgomery-Asberg Depression Rating Scale scores improved from baseline (p < .01). Two treated subgroups were identified: 10 patients (67%) had primary conversion disorder, of whom 8 had marked motor and global improvements with 7 complete remissions, and 5 (33%) had primary hypochondriasis, somatization disorder, or probable factitious disorder/malingering, of whom none improved. All of the patients with primary conversion disorder had a current or previous depressive or anxiety disorder compared with 40% (N = 2) of the patients with additional somatoform diagnoses. Our preliminary findings suggest that chronic PMD with primary conversion symptoms and with recent or current depression or anxiety may respond to antidepressants. Further well-designed studies, now under way, are required

Antidepressants, anxiolytics, and hypnotics in pregnancy and lactation

PubMed Central

Ram, Daya; Gandotra, S.

2015-01-01

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

Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression.

PubMed

Haenisch, Britta; Bilkei-Gorzo, Andras; Caron, Marc G; Bönisch, Heinz

2009-10-01

Diverse factors such as changes in neurotrophins and brain plasticity have been proposed to be involved in the actions of antidepressant drugs (ADs). However, in mouse models of depression based on chronic stress, it is still unclear whether simultaneous changes in behavior and neurotrophin expression occur and whether these changes can be corrected or prevented comparably by chronic administration of ADs or genetic manipulations that produce antidepressant-like effects such as the knockout of the norepinephrine transporter (NET) gene. Here we show that chronic restraint or social defeat stress induce comparable effects on behavior and changes in the expression of neurotrophins in depression-related brain regions. Chronic stress caused down-regulation of BDNF, nerve growth factor, and neurotrophin-3 in hippocampus and cerebral cortex and up-regulation of these targets in striatal regions. In wild-type mice, these effects could be prevented by concomitant chronic administration of five pharmacologically diverse ADs. In contrast, NET knock out (NETKO) mice were resistant to stress-induced depressive-like changes in behavior and brain neurotrophin expression. Thus, the resistance of the NETKO mice to the stress-induced depression-associated behaviors and biochemical changes highlight the importance of noradrenergic pathways in the maintenance of mood. In addition, these mice represent a useful model to study depression-resistant behaviors, and they might help to provide deeper insights into the identification of downstream targets involved in the mechanisms of antidepressants.

Sexual side effects of antidepressant drugs.

PubMed

Gelenberg, A J; Delgado, P; Nurnberg, H G

2000-06-01

Sexual functioning often suffers during depression, although depressed people continue to value sex. Many popular antidepressants further impair sexual functioning, with highly serotonergic agents affecting orgasm and libido prominently. This paper addresses clinical assessment of sexual side effects from antidepressant drugs and reviews treatment strategies, including purported antidotes. We pay particular attention to sildenafil, on which there are impressive data and ongoing controlled studies.

Religiousness, social support and the use of antidepressants among the elderly: a population-based study.

PubMed

Vicente, Adriano Roberto Tarifa; Castro-Costa, Érico; Firmo, Josélia de Oliveira Araújo; Lima-Costa, Maria Fernanda; Loyola Filho, Antônio Ignácio de

2018-03-01

The purpose of the study was to investigate whether religiousness and social support were associated with the use of antidepressants among community-dwelling elders. The research involved 1,606 older adults who make up the cohort of Bambuí Project, a study on ageing and health. The dependent variable was the use of antidepressants in the last 90 days, and the exposures of interest were social support and religiousness. Logistic regression was used to test the associations and to estimate crude and adjusted Odds Ratio and their 95% confidence intervals. The chances of use of antidepressants were significantly lower among older people with higher level of religiosity (OR = 0.45; 95% CI: 0.29 to 0.70), but none of the descriptors social support was associated with the event. In this population, it is possible that religion occupies a prominent role in the arsenal of health problems coping strategies, especially mental. Health professionals attending this particular segment of the population (elderly people with depressive disorders) should consider religiousness of patients when the proposed guidelines and treatment in coping with their mental suffering.

Efficacy and feasibility of antidepressants for the prevention of migraine in adults: a meta-analysis.

PubMed

Xu, X-M; Yang, C; Liu, Y; Dong, M-X; Zou, D-Z; Wei, Y-D

2017-08-01

Migraine has greatly impacted the quality of life for migraineurs and was ranked as the seventh highest specific cause of disability worldwide in 2012. Because of the role of serotonin in migraine mechanisms, antidepressants have been used in the prevention of migraine. However, the role of antidepressants for migraine prophylaxis in adults has not been completely established. Our aim was systematically to assess the efficacy and feasibility of antidepressants for the prevention of migraine in adults based on currently available literature. A comprehensive search of databases was conducted including the Cochrane, PubMed, Web of Science and Embase databases from inception to July 2016. Randomized controlled trials that assigned adults with a clinical diagnosis of migraine to antidepressant or placebo treatment were included. The primary outcome was the reduction of migraine frequency or index. Overall, 16 randomized controlled trials including 1082 participants were identified. Antidepressants had a significant advantage over placebo in reducing the migraine frequency or index of adults with a standardized mean difference of -0.79 [95% confidence interval (CI) -1.13 to -0.45, P < 0.00001]. Patients receiving antidepressant therapy were more likely to experience an at least 50% reduction of headache burden than those receiving placebo (28.9% vs. 20.2%; risk ratio 1.40; 95% CI 0.97-2.02; P = 0.07). However, antidepressants were less well tolerated than placebo because of some adverse events (risk ratio 1.74, 95% CI 1.05-2.89, P = 0.03). Antidepressants are effective in the prophylaxis of migraine in adults, but the level of evidence for antidepressants except for amitriptyline seems to be quite shaky. © 2017 EAN.

Natural and engineered coding variation in antidepressant-sensitive serotonin transporters.

PubMed

Ye, R; Blakely, R D

2011-12-01

The presynaptic serotonin (5-HT) transporter (SERT) is a key regulator of 5-HT signaling and is a major target for antidepressant medications and psychostimulants. In recent years, studies of natural and engineered genetic variation in SERT have provided new opportunities to understand structural dimensions of drug interactions and regulation of the transporter, to explore 5-HT contributions to antidepressant action, and to assess the impact of SERT-mediated 5-HT contributions to neuropsychiatric disorders. Here we review three examples from our recent studies where genetic changes in SERT, identified or engineered, have led to new models, findings, and theories that cast light on new dimensions of 5-HT action in the CNS and periphery. First, we review our work to identify specific residues through which SERT recognizes antagonists, and the conversion of this knowledge to the creation of mice lacking high-affinity antidepressant and cocaine sensitivity. Second, we discuss our studies of functional coding variation in SERT that exists in commonly used strains of inbred mice, and how this variation is beginning to reveal novel 5-HT-associated phenotypes. Third, we review our identification and functional characterization of multiple, hyperactive SERT coding variants in subjects with autism. Each of these activities has driven the development of new model systems that can be further exploited to understand the contribution of 5-HT signaling to risk for neuropsychiatric disorders and their treatment. Copyright © 2011. Published by Elsevier Ltd.

NATURAL AND ENGINEERED CODING VARIATION IN ANTIDEPRESSANT-SENSITIVE SEROTONIN TRANSPORTERS

PubMed Central

YE, R.; BLAKELY, R. D.

2013-01-01

The presynaptic serotonin (5-HT) transporter (SERT) is a key regulator of 5-HT signaling and is a major target for antidepressant medications and psychostimulants. In recent years, studies of natural and engineered genetic variation in SERT have provided new opportunities to understand structural dimensions of drug interactions and regulation of the transporter, to explore 5-HT contributions to antidepressant action, and to assess the impact of SERT-mediated 5-HT contributions to neuropsychiatric disorders. Here we review three examples from our recent studies where genetic changes in SERT, identified or engineered, have led to new models, findings, and theories that cast light on new dimensions of 5-HT action in the CNS and periphery. First, we review our work to identify specific residues through which SERT recognizes antagonists, and the conversion of this knowledge to the creation of mice lacking high-affinity antidepressant and cocaine sensitivity. Second, we discuss our studies of functional coding variation in SERT that exists in commonly used strains of inbred mice, and how this variation is beginning to reveal novel 5-HT-associated phenotypes. Third, we review our identification and functional characterization of multiple, hyperactive SERT coding variants in subjects with autism. Each of these activities has driven the development of new model systems that can be further exploited to understand the contribution of 5-HT signaling to risk for neuropsychiatric disorders and their treatment. PMID:21893166

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

PubMed

Bengtson, Angela M; Pence, Brian W; 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

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. 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. 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 non-Hispanics. In our cohort

Antidepressant drugs and the risk of suicide in children and adolescents.

PubMed

Isacsson, Göran; Rich, Charles L

2014-04-01

Government agencies have issued warnings about the use of antidepressant medications in children, adolescents, and young adults since 2003. The statements warn that such medications may cause de novo 'suicidality' in some people. This review explores the data on the treatment of depression that led to these warnings and subsequent data that are relevant to the warnings. It also addresses the effectiveness of antidepressant treatment in general and the relationship of suicide rates to antidepressant treatment. It concludes that the decisions for the 'black box' warnings were based on biased data and invalid assumptions. Furthermore, the decisions were unsupported by the observational data regarding suicide in young people that existed in 2003. The following recommendations would seem to follow from these observations. First, drug authorities should re-evaluate the basis for their imposed warnings on antidepressant medicines, and analyze the actual public health consequences the warnings have had. In the absence of substantial evidence supporting the warnings, they should be removed. Second, physicians and other providers with prescription privileges should continue to be educated regarding the importance of aggressively treating depression in young people, using antidepressants when indicated. Third, physicians and other professionals who treat depressed young people must always be aware of the risk of suicide (albeit quite low) and observe them closely for any signs of increased risk of suicide. This is necessary regardless of the type of treatment being provided.

X-ray structure of the dopamine transporter in complex with tricyclic antidepressant

PubMed Central

Penmatsa, Aravind; Wang, Kevin H.; Gouaux, Eric

2013-01-01

Antidepressants targeting Na+/Cl−-coupled neurotransmitter uptake define a major therapeutic strategy to treat clinical depression and neuropathic pain. However, identifying the molecular interactions that underlie the pharmacological activity of these transport inhibitors and thus the mechanism by which the inhibitors lead to increased synaptic neurotransmitter levels has proven elusive. Here we present the crystal structure of the Drosophila melanogaster dopamine transporter (dDAT) at 3.0 Å resolution bound to the tricyclic antidepressant nortriptyline. The transporter is locked in an outward-open conformation with nortriptyline wedged between TMs1/6 and 3/8, blocking the transporter from binding substrate and from isomerizing to an inward facing conformation. While the overall structure of dDAT is similar to that of its prokaryotic relative LeuT, there are multiple distinctions that include a kink in TM12 halfway across the membrane bilayer, a latch-like C-terminal helix that caps the cytoplasmic gate, and a cholesterol molecule wedged within a groove formed by TMs 1a, 5 and 7. Taken together, the dDAT structure reveals the molecular basis for antidepressant action on sodium-coupled neurotransmitter symporters and illuminates critical elements of eukaryotic transporter structure and modulation by lipids, thus expanding our understanding of mechanism and regulation of neurotransmitter uptake at chemical synapses. PMID:24037379

Clinical variables related to antidepressant-induced mania in bipolar disorder.

PubMed

Mundo, Emanuela; Cattaneo, Elisabetta; Russo, Michela; Altamura, A Carlo

2006-06-01

The development of mania or hypomania during antidepressant treatment is a serious complication of the clinical management of bipolar disorder (BP). The primary aim of this study was to evaluate the clinical variables related to antidepressant-induced mania or hypomania (AIM) in patients with BP. DSM-IV BP-I or BP-II patients who had had at least one depressive episode treated with antidepressants were considered. Patients were subdivided into two groups according to the presence (n = 30) or absence (n = 106) of manic or hypomanic episodes occurring during antidepressant treatment. Possible predictive clinical variables of AIM were considered: gender, diagnostic subtype, age at onset, duration of illness, duration of untreated illness, type of antidepressant administered, number of previous spontaneous hypomanic or manic episodes, number of previous depressive episodes, presence of lifetime suicide attempts, presence of mood stabilizer treatments, presence of psychotic symptoms during spontaneous episodes, family history for psychiatric disorders in first degree relatives. Data were compared between the two groups, with (AIM+) and without (AIM-) antidepressant-induced mania, using Student's t tests and chi-square tests. The lack of mood stabilizer treatments during antidepressant therapy (chi-square = 37.602, df = 1, p < 0.001) and the exposure to tricyclic antidepressants (chi-square = 4.901, df = 1, p < 0.05) resulted significantly associated to the development of AIM. This study was not done under controlled conditions and the relatively small sample studied warrants further replications. These results point out the risk of mania induction associated to the use of tricyclic antidepressants in BP patients, mainly in absence of adequate mood stabilizers.

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.

PubMed

Kuyken, Willem; Hayes, Rachel; Barrett, Barbara; Byng, Richard; Dalgleish, Tim; Kessler, David; Lewis, Glyn; Watkins, Edward; Brejcha, Claire; Cardy, Jessica; Causley, Aaron; Cowderoy, Suzanne; Evans, Alison; Gradinger, Felix; Kaur, Surinder; Lanham, Paul; Morant, Nicola; Richards, Jonathan; Shah, Pooja; Sutton, Harry; Vicary, Rachael; Weaver, Alice; Wilks, Jenny; Williams, Matthew; Taylor, Rod S; Byford, Sarah

2015-07-04

Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18

Continued antidepressant treatment and suicide in patients with depressive disorder.

PubMed

Søndergård, Lars; Lopez, Ana Garcia; Andersen, Per Kragh; Kessing, Lars Vedel

2007-01-01

Antidepressant use in Denmark, as in many developed countries, has substantially increased during recent years, coinciding with a decreasing suicide rate. In a nationwide observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark from 1995 to 2000, we investigated the relation between continued treatment with antidepressants and suicide in a population of all patients discharged from hospital psychiatry with a diagnosis of depressive disorder. Patients discharged from hospital psychiatry with a diagnosis of depressive disorder had a highly increased rate of suicide. Those who continued treatment with antidepressants had a decreased rate of suicide compared with those who purchased antidepressants once (rate ratio: 0.31, 95% confidence interval: 0.26-0.36). Further, the rate of suicide decreased consistently with the number of prescriptions. On individualized data from a cohort of patients with a known history of depressive disorder, continued antidepressant treatment was associated with reduced risk of suicide.

Clinical application of antidepressant pharmacogenetics: considerations for the design of future studies.

PubMed

Fabbri, Chiara; Serretti, Alessandro

2018-06-12

A frustrating inertia has affected the development of clinical applications of antidepressant pharmacogenetics and personalized treatments of depression are still lacking 20 years after the first findings. Candidate gene studies provided replicated findings for some polymorphisms, but each of them shows at best a small effect on antidepressant efficacy and the cumulative effect of different polymorphisms is unclear. Further, no candidate was immune by at least some negative studies. These considerations give rise to some concerns about the clinical benefits of currently available pharmacogenetic tests since they are based on the results of candidate gene studies. Clinical guidelines in fact suggest that only polymorphisms that alter cytochrome 2D6 or 2C19 enzymatic activity probably provide useful clinical indications, while variants in genes involved in antidepressant pharmacodynamics have no recommended clinical applications. The present review discusses possible strategies to facilitate the identification of genetic biomarkers with clinical usefulness in guiding antidepressant treatments. These include analysis methods for the study of the polygenic/omnigenic nature of antidepressant response, the prioritization of polymorphisms on the basis of functional considerations, the incorporation of clinical-demographic predictors in pharmacogenetic studies (e.g. mixed polygenic and clinical risk scores), the application of methodological improvements to the design of future studies in order to maximize the comparability of results and improve power. Copyright © 2018. Published by Elsevier B.V.

A systematic review of the utility of antidepressant pharmacotherapy in the treatment of vulvodynia pain.

PubMed

Leo, Raphael J; Dewani, Seema

2013-10-01

  Antidepressants have often been recommended as a potential treatment for the management of vulvodynia. However, review of the evidence supporting this recommendation has not been systematically assessed.   To evaluate the efficacy of antidepressant pharmacotherapy in the treatment of vulvodynia.   An assessment of the methodological quality of published reports addressing the utility of antidepressants in the treatment of vulvodynia was undertaken. Several secondary outcomes generated in the existing literature were also examined.   A comprehensive search of the available literature was conducted.   The search yielded 13 published reports, i.e., 2 randomized controlled trials, 1 quasi-experimental trial, 7 non-experimental studies, and 3 case reports. A number of methodological shortcomings were identified in several of the reports with respect to study design including lack of clear inclusion/exclusion criteria, small sample sizes, lack of comparison groups, insufficient blinding, among others. The vast majority of studies utilized tricyclic antidepressants (TCAs). Evidence supporting the benefits of TCAs studied to date was limited, i.e., based largely upon descriptive reports but unsubstantiated by randomized controlled trials. There were no systematic investigations into the comparative efficacy of different antidepressant classes in the treatment of vulvodynia.   There is insufficient evidence to support the recommendation of antidepressant pharmacotherapy in the treatment of vulvodynia. Although some vulvodynia-afflicted patients derive symptom relief from antidepressants, additional research is required to identify those characteristics that would predict those patients for whom antidepressants are more likely to be effective. © 2012 International Society for Sexual Medicine.

Role of the nicotinic receptor β4 subunit in the antidepressant activity of novel N,6-dimethyltricyclo[5.2.1.0²,⁶]decan-2-amine enantiomers.

PubMed

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

2013-10-11

The role of the nicotinic receptor β4 subunit in the antidepressant activity of N,6-dimethyltricyclo[5.2.1.0(2,6)]decan-2-amine enantiomers was investigated using wild-type (β4+/+) and knockout (β4-/-) mice. Mice were injected (i.p.) with saline (control) or with either enantiomer (1.0mg/kg base drug) daily for the first two weeks. Forced swim tests (FST) were performed on Day 1 to determine the acute effect of each enantiomer, and on Day 7 and 14, to determine the chronic activity. To examine the remnant effects after drug treatment, a withdrawal period of two more weeks was continued with FSTs performed on Day 21 and 28. Our results indicate that: (1) the acute antidepressant effect elicited by the (S,S)-enantiomer is observed in β4+/+ mice from both sexes, whereas the effect elicited by the (R,R)-enantiomer is only observed in male β4+/+ mice. There is no antidepressant effect for both novel compounds on male and female β4-/- mice, (2) the chronic antidepressant effect elicited by both enantiomers is observed in β4+/+, but not in β4-/-, mice from both sexes, and (3) the residual antidepressant effect mediated by each enantiomer after withdrawal was observed only in female β4+/+ mice. Our results clearly indicate that β4-containing AChRs are targets for the antidepressant activity of these compounds, and that this activity is gender-dependent. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pharmacogenetics and Imaging-Pharmacogenetics of Antidepressant Response: Towards Translational Strategies.

PubMed

Lett, Tristram A; Walter, Henrik; Brandl, Eva J

2016-12-01

Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment. The purpose of this article is to provide a comprehensive review of the advances made in the field of pharmacogenetics of antidepressant efficacy and side effects, imaging findings of antidepressant response, and the latest results in the expanding field of imaging-pharmacogenetics studies. We suggest there is mounting evidence that genetic factors exert their impact on treatment response by influencing brain structural and functional changes during antidepressant treatment, and combining neuroimaging and genetic methods may be a more powerful way to detect biological mechanisms of response than either method alone. The most promising imaging-pharmacogenetics findings exist for the SCL6A4 gene, with converging associations with antidepressant response, frontolimbic predictors of affective symptoms, and normalization of frontolimbic activity following antidepressant treatment. More research is required before imaging-pharmacogenetics informed personalized medicine can be applied to antidepressant treatment; nevertheless, inroads have been made towards assessing genetic and neuroanatomical liability and potential clinical application.

Progress and prospects in pharmacogenetics of antidepressant drugs.

PubMed

Fabbri, Chiara; Crisafulli, Concetta; Calabrò, Marco; Spina, Edoardo; Serretti, Alessandro

2016-10-01

Depression is responsible for the most part of the personal and socio-economic burden due to psychiatric disorders. Since antidepressant response clusters in families, pharmacogenetics represents a meaningful tool to provide tailored treatments and improve the prognosis of depression. This review aims to summarize and discuss the pharmacogenetics of antidepressant drugs in major depressive disorder, with a focus on the most replicated genes, genome-wide association studies (GWAS), but also on the findings provided by new and promising analysis methods. In particular, multimarker tests such as pathway analysis and polygenic risk scores increase the power of detecting associations compared to the analysis of individual polymorphisms. Since genetic variants are not necessarily associated with a change in protein level, gene expression studies may provide complementary information to genetic studies. Finally, the pharmacogenetic tests that have been investigated for clinical application are discussed. Despite the lack of widespread clinical applications, preliminary results suggest that pharmacogenetics may be useful to guide antidepressant treatment. The US Food and Drug Administration included pharmacogenetic indications in the labeling of several antidepressants. This represented an important official recognition of the clinical relevance of genetic polymorphisms in antidepressant treatment.

Antidepressants for the treatment of depression in people with cancer.

PubMed

Ostuzzi, Giovanni; Matcham, Faith; Dauchy, Sarah; Barbui, Corrado; Hotopf, Matthew

2018-04-23

cause, we found no difference between antidepressants as a class compared with placebo (RR 0.85, 95% CI 0.52 to 1.38, seven RCTs, 479 participants; very low certainty evidence), and between SSRIs and tricyclic antidepressants (RR 0.83, 95% CI 0.53 to 1.30, three RCTs, 237 participants). We downgraded the certainty (quality) of the evidence because the included studies were at an unclear or high risk of bias due to poor reporting, imprecision arising from small sample sizes and wide confidence intervals, and inconsistency due to statistical or clinical heterogeneity. Despite the impact of depression on people with cancer, the available studies were very few and of low quality. This review found very low certainty evidence for the effects of these drugs compared with placebo. On the basis of these results, clear implications for practice cannot be deduced. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent to prescribe may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. To better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.

Antidepressant-like activity of the neuropeptide Y Y5 receptor antagonist Lu AA33810: behavioral, molecular, and immunohistochemical evidence.

PubMed

Domin, Helena; Szewczyk, Bernadeta; Pochwat, Bartłomiej; Woźniak, Monika; Śmiałowska, Maria

2017-02-01

It has recently been found that chronic treatment with the highly selective, brain-penetrating Y5 receptor antagonist, Lu AA33810 [N-[[trans-4-[(4,5-dihydro [1] benzothiepino[5,4-d] thiazol-2-yl) amino] cyclohexyl]methyl]-methanesulfonamide], produces antidepressant-like effects in the rat chronic mild stress model. In the present study, we investigated the possible antidepressant-like activity of Lu AA33810 in rats subjected to glial ablation in the prefrontal cortex (PFC) by the gliotoxin L-AAA, which is an astroglial degeneration model of depression. We observed that Lu AA33810 administered intraperitoneally at a single dose of 10 mg/kg both reversed depressive-like behavioral changes in the forced swim test (FST) and prevented degeneration of astrocytes in the mPFC. The mechanism of antidepressant and glioprotective effects of Lu AA33810 has not been studied, so far. We demonstrated the contribution of the noradrenergic rather than the serotonergic pathway to the antidepressant-like action of Lu AA33810 in the FST. Moreover, we found that antidepressant-like effect of Lu AA33810 was connected with the influence on brain-derived neurotrophic factor (BDNF) protein expression. We also demonstrated the antidepressant-like effect of Lu AA33810 in the FST in rats which did not receive the gliotoxin. We found that intracerebroventricular injection of the selective MAPK/ERK inhibitor U0126 (5 μg/2 μl) and the selective PI3K inhibitor LY294002 (10 nmol/2 μl) significantly inhibited the anti-immobility effect of Lu AA33810 in the FST in rats, suggesting that MAPK/ERK and PI3K signaling pathways could be involved in the antidepressant-like effect of Lu AA33810. Our results indicate that Lu AA33810 exerts an antidepressant-like effect and suggest the Y5 receptors as a promising target for antidepressant therapy.

Association between Antidepressants and Fall-Related Injuries among Long-Term Care Residents.

PubMed

Macri, Jennifer C; Iaboni, Andrea; Kirkham, Julia G; Maxwell, Colleen; Gill, Sudeep S; Vasudev, Akshya; Whitehead, Marlo; Seitz, Dallas P

2017-12-01

Antidepressants are associated with an increased risk of falls although little is known of the comparative risks of different types of antidepressants or individuals who are at greatest risk for falls. We examined the association between new use of antidepressants and fall-related injuries among older adults in long-term care (LTC). This was a matched, retrospective cohort study involving LTC residents in Ontario, Canada, from 2008 to 2014. New users of antidepressants were matched to non-users of antidepressants. The primary outcome was any fall resulting in an emergency department (ED) visit or hospitalization within 90 days after exposure. Secondary outcomes included hip fractures, wrist fractures, and falls reported in LTC. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval associated with antidepressants and outcomes. New users of any antidepressant had an increased risk of ED visits or hospitalization for falls within 90 days when compared with individuals not receiving antidepressants (5.2% versus 2.8%; adjusted OR: 1.9, 95% CI: 1.7-2.2). Antidepressants were also associated with an increased risk of all secondary outcomes. The increased risk of fall-related injuries was evident among selective-serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, trazodone, and across multiple patient subgroups. New use of antidepressants is associated with significantly increased risk of falls and fall-related injuries among LTC residents across different patient subgroups and antidepressant classes. The potential risk of fall-related outcomes should be carefully considered when initiating antidepressants among older adults in LTC. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

IC Treatment: Antidepressants

MedlinePlus

... prescribes you a TCA, take it in the early evening to eliminate unwanted morning drowsiness. For constipation, increase the amount of fiber in your diet. Consider taking Metamucil or a stool softener such as Colace. Pregnancy & Warnings None of the antidepressants in any of ...

Influence of psychotherapist density and antidepressant sales on suicide rates.

PubMed

Kapusta, N D; Niederkrotenthaler, T; Etzersdorfer, E; Voracek, M; Dervic, K; Jandl-Jager, E; Sonneck, G

2009-03-01

Antidepressant sales and suicide rates have been shown to be correlated in industrialized countries. The aim was to study the possible effects of psychotherapy utilization on suicide rates. We assessed the impact of antidepressant sales and psychotherapist density on suicide rates between 1991 and 2005. To adjust for serial correlation in time series, three first-order autoregressive models adjusted for per capita alcohol consumption and unemployment rates were employed. Antidepressant sales and the density of psychotherapists in the population were negatively associated with suicide rates. This study provides evidence that decreasing suicide rates were associated with both increasing antidepressant sales and an increasing density of psychotherapists. The decrease of suicide rates could reflect a general improvement in mental health care rather than being caused by antidepressant sales or psychotherapist density alone.

Looking for bipolarity in antidepressant discontinuation manic states: Update and diagnostic considerations of the phenomenon.

PubMed

Abou Kassm, Sandra; Naja, Wadih

2018-08-01

Antidepressant withdrawal manic states are intriguing and under-recognized phenomena. The associated patho-physiological pathways are ill defined and the inclusion of the phenomena in the bipolar spectrum disorders is questionable. This study aims to update a review on antidepressant discontinuation manic states published in 2008 and to look for hints alluding to bipolar disorder in the affected published cases and in the literature. It also reviews the different hypotheses proposed to explain discontinuation mania. We searched Pubmed using the key words: 'antidepressant withdrawal' or 'antidepressant discontinuation' plus 'mania' or 'hypomania' from January 2008 until January 2018. Five new eligible reports were identified since the last review in 2008, involving the antidepressants Amitriptyline, Fluoxetine, Escitalopram and Mirtazapine. Hypotheses involve the implication of Catecholamines, Acetylcholine and Serotonin in the pathophysiology of this paradoxical phenomenon. Careful analysis of the total 29 cases revealed psychiatric histories in favor of a bipolar spectrum disorder in 12 individuals while five were already known to have bipolar disorder. This review is based on case reports with associated recall bias, and lack of in-depth description at times. Antidepressant discontinuation manic or hypomanic states do not occur randomly. An individual susceptibility to bipolar disorder must be considered. Copyright © 2018 Elsevier B.V. All rights reserved.

Antidepressant Prescription and Suicide Rates: Effect of Age and Gender

ERIC Educational Resources Information Center

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

2008-01-01

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

Milnacipran versus other antidepressive agents for depression.

PubMed

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

2009-07-08

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. 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. 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 hand-searched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. 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. 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. 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 rather wide and there were no statistically significant differences in efficacy, acceptability and

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

PubMed Central

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

2015-01-01

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

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

Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents.

PubMed

Gibbons, Robert D; Coca Perraillon, Marcelo; Hur, Kwan; Conti, Rena M; Valuck, Robert J; Brent, David A

2015-02-01

In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding. We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding. For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone. Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth. Copyright © 2014 John Wiley & Sons, Ltd.

Misleading advertising for antidepressants in Sweden: a failure of pharmaceutical industry self-regulation.

PubMed

Zetterqvist, Anna V; Mulinari, Shai

2013-01-01

The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994-2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system's failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self-regulatory settings, and if appropriate measures are not taken to

Emotional blunting with antidepressant treatments: A survey among depressed patients.

PubMed

Goodwin, G M; Price, J; De Bodinat, C; Laredo, J

2017-10-15

Emotional blunting is regularly reported in depressed patients on antidepressant treatment but its actual frequency is poorly understood. We have previously used qualitative methods to develop an appropriate scale, the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA). Six hundred and sixty nine depressed patients on treatment and 150 recovered (formerly depressed) controls (aged ≥18 years) participated in this internet-based survey. The rate of emotional blunting in treated depressed patients was 46%, slightly more frequent in men than women (52% versus 44%) and in those with higher Hospital Anxiety and Depression (HAD) scale scores. There was no difference according to antidepressant agent, though it appeared less frequent with bupropion. Depressed patients with emotional blunting had much higher total blunting scores on OQESA than controls (42.83 ± 14.73 versus 25.73 ± 15.00, p < 0.0001) and there was a correlation between total blunting score and HAD-Depression score (r = 0.521). Thus, those with HAD-D score >7 (n = 170) had a higher total questionnaire score, 49.23±12.03, than those with HAD-D score ≤7 (n = 140), 35.07 ± 13.98, and the difference between the two groups was highly significant. However, patients with HAD-D score ≤7 (n = 140) had a higher total score (35.07 ± 13.98) than the recovered controls (n = 150) (25.73 ± 15.00), and the difference between the two groups was significant. Among the patients with emotional blunting, 37% had a negative perception of their condition and 38% positive. Men reported a more negative perception than women (p=0.008), and patients with a negative perception were more likely to have higher HAD scores. Higher levels of emotional blunting are associated with a more negative perception of it by the patient (r = -0.423). Include self-evaluation and the modest size of the sample for detection of differences between antidepressants. Emotional blunting is reported by nearly half of

Generic penetration in the retail antidepressant market.

PubMed

Ventimiglia, Jeffrey; Kalali, Amir H

2010-06-01

In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Characteristics associated with purchasing antidepressant or antianxiety medications through primary care in Israel.

PubMed

Ayalon, Liat; Gross, Revital; Yaari, Aviv; Feldhamer, Elan; Balicer, Ran; Goldfracht, Margalit

2011-09-01

This study analyzed the role of patient and physician characteristics associated with the purchase of antidepressant or antianxiety medications in Israel, a country that has a universal health care system. A national sample of 30,000 primary care patients over the age of 22 was randomly drawn from the registry of the largest health care fund in Israel. Data concerning medication purchase between January and December 2006 were extracted. Physician and patient characteristics were merged with Israel's unique identification number. Multilevel analysis was conducted to identify patient- and physician-level predictors of medication purchase. Overall, 19% (N = 4,762) of the sample purchased antidepressant or antianxiety medications. Individuals with greater general medical and psychiatric comorbidity were more likely to purchase antidepressant or antianxiety medications. Older adults, women, those of higher socioeconomic status, and immigrants (with the exception of Jews born in Asia or Africa) were also more likely to purchase medications. Arabs and Jews born in Asia and Africa were less likely to purchase medications even after all other variables were accounted for. Physician characteristics were minimally associated with the purchase of medications. The findings demonstrate that despite universal health care access, there were variations by population groups. Educational efforts should target patients as well as physicians.

Prevalence and characteristics of antidepressant drug prescriptions in older Italian patients.

PubMed

Marengoni, A; Bianchi, G; Nobili, A; Tettamanti, M; Pasina, L; Corrao, S; Salerno, F; Iorio, A; Marcucci, M; Mannucci, P M

2012-04-01

During last few decades, the proportion of elderly persons prescribed with antidepressants for the treatment of depression and anxiety has increased. The aim of this study was to evaluate prevalence of antidepressant prescription and related factors in elderly in-patients, as well as the consistency between prescription of antidepressants and specific diagnoses requiring these medications. Thirty-four internal medicine and four geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI study during 2008. In all, 1,155 in-patients, 65 years or older, were enrolled. Prevalence of the use of antidepressants was calculated at both admission and discharge. Logistic regression was used to evaluate the association between patients' characteristics (age, gender, Charlson Index, number of drugs, specific diseases, other psychotropic medications) and the prescription of antidepressants. The number of patients treated with antidepressant medication at hospital admission was 115 (9.9%) and at discharge 119 (10.3%). In a multivariate analysis, a higher number of drugs (OR = 1.2; 95% CI = 1.1-1.3), use of anxiolytic drugs (OR = 2.1; 95% CI = 1.2-3.6 and OR = 3.8; 95% CI = 2.1-6.8), and a diagnosis of dementia (OR = 6.1; 95% CI = 3.1-11.8 and OR = 5.8; 95% CI = 3.3-10.3, respectively, at admission and discharge) were independently associated with antidepressant prescription. A specific diagnosis requiring the use of antidepressants was present only in 66 (57.4%) patients at admission and 76 (66.1%) at discharge. Antidepressants are commonly prescribed in geriatric patients, especially in those receiving multiple drugs, other psychotropic drugs, and those affected by dementia. There is an inconsistency between the prescription of antidepressants and a specific diagnosis that the hospitalization only slightly improves.

Biomarkers of anhedonic-like behavior, antidepressant drug refraction, and stress resilience in a rat model of depression.

PubMed

Christensen, T; Bisgaard, C F; Wiborg, O

2011-11-24

The aim of the present study was to identify potential biomarkers for depression in the search for novel disease targets and treatment regimens. Furthermore, the study includes a search for biomarkers involved in treatment resistance and stress resilience in order to investigate mechanisms underlying antidepressant drug refraction and stress-coping strategies. Depression-related transcriptomic changes in gene expression profiles were investigated in laser-captured microdissected (LCM) rat hippocampal granular cell layers (GCL) using the chronic mild stress (CMS) rat model of depression and chronic administration of two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline. CMS rats were segregated into diverging groups according to behavioral readouts, and under stringent constraints, the associated differential gene regulations were analyzed. Accordingly, we identified four genes associated with recovery, two genes implicated in treatment resistance, and three genes involved in stress resilience. The identified genes associated with mechanisms of cellular plasticity, including signal transduction, cell proliferation, cell differentiation, and synaptic release. Hierarchical clustering analysis confirmed the subgroup segregation pattern in the CMS model. Thus antidepressant treatment refractors cluster with anhedonic-like rats, and, interestingly, stress-resilient rats cluster with rats undergoing antidepressant-mediated recovery from anhedonia, suggesting antidepressant mechanisms of action to emulate endogenous stress-coping strategies. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Risk of fractures with selective serotonin-reuptake inhibitors or tricyclic antidepressants.

PubMed

Ginzburg, Regina; Rosero, Enma

2009-01-01

To evaluate the literature associating the risk of fracture during antidepressant therapy. Literature was identified via MEDLINE (1970-August 2008) using the search terms selective serotonin-reuptake inhibitors, tricyclic antidepressants, antidepressants, and fracture. Reference citations from publications identified were also reviewed. All articles in English identified from the data sources were evaluated. Selective serotonin-reuptake inhibitors (SSRIs) are generally prescribed over other classes of antidepressants because they are considered to be relatively safer. Recent evidence, however, suggests that SSRIs may be associated with an increased risk of fractures. Thirteen clinical studies were identified in the literature search (7 case controls, 5 prospective cohorts, 1 cross-sectional). Most studies compared SSRIs with tricyclic antidepressants (TCAs) and found similar or greater risk of fracture associated with use of an SSRI. This risk appeared to be highest at the beginning of therapy with TCAs and eventually diminished. SSRI risk tended to increase slightly over time. No risk was seen with other classes of antidepressants. However, the number of patients using antidepressants was low. There may be a possible correlation with SSRI or TCA use and risk of fracture. Prospective, randomized controlled trials with sufficient patient samples are needed to verify this finding.

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Voluntary Exercise Produces Antidepressant and Anxiolytic Behavioral Effects in Mice

PubMed Central

Duman, Catharine H.; Schlesinger, Lee; Russell, David S.; Duman, Ronald S.

2008-01-01

Reports of beneficial effects of exercise on psychological health in humans are increasingly supported by basic research studies. Exercise is hypothesized to regulate antidepressant-related mechanisms and we therefore characterized the effects of chronic exercise in mouse behavioral paradigms relevant to antidepressant actions. Mice given free access to running wheels showed antidepressant-like behavior in learned helplessness, forced-swim (FST) and tail suspension paradigms. These responses were similar to responses of antidepressant drug-treated animals. When tested under conditions where locomotor activity was not altered, exercising mice also showed reduced anxiety compared to sedentary control mice. In situ hybridization analysis showed that BDNF mRNA was increased in specific subfields of hippocampus after wheel running. We chose one paradigm, the FST, in which to investigate a functional role for brain-derived neurotrophic factor (BDNF) in the behavioral response to exercise. We tested mice heterozygous for a deletion of the BDNF gene in the FST after wheel-running. Exercising wild-type mice showed the expected antidepressant-like behavioral response in the FST but exercise was ineffective in improving FST performance in heterozygous BDNF knockout mice. A possible functional contribution of a BDNF signaling pathway to FST performance in exercising mice was investigated using the specific MEK inhibitor PD184161 to block the MAPK signaling pathway. Subchronic administration of PD184161 to exercising mice blocked the antidepressant-like behavioral response seen in vehicle-treated exercising mice in the FST. In summary, chronic wheel-running exercise in mice results in antidepressant-like behavioral changes that may involve a BDNF related mechanism similar to that hypothesized for antidepressant drug treatment. PMID:18267317

Generic Penetration in the Retail Antidepressant Market

PubMed Central

Kalali, Amir H.

2010-01-01

In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty. PMID:20622940

Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.

PubMed

Kotagale, Nandkishor R; Tripathi, Sunil J; Aglawe, Manish M; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2013-06-01

Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10-20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40 μg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5 μg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 μg/mouse, icv) and agmatinase inhibitor, arcaine (50 μg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015 mg/kg, ip) and imidazoline I2 receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5mg/kg, ip). Conversely, prior administration of I1 receptor antagonist, efaroxan (1mg/kg, ip) and I2 receptor antagonist, idazoxan (0.25mg/kg, ip) blocked the antidepressant like effect of bupropion and its synergistic combination with agmatine. These results demonstrate involvement of agmatine in the antidepressant like effect of bupropion and suggest agmatine and imidazoline receptors as a potential therapeutic target for the treatment of depressive disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?

PubMed Central

Cardamone, L; Salzberg, MR; O'Brien, TJ; Jones, NC

2013-01-01

There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer (‘second generation’) antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term ‘epileptogenesis’: the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section. PMID:23146067

Surfactant adsorption and aggregate structure of silica nanoparticles: a versatile stratagem for the regulation of particle size and surface modification

NASA Astrophysics Data System (ADS)

Chaudhary, Savita; Rohilla, Deepak; Mehta, S. K.

2014-03-01

The area of silica nanoparticles is incredibly polygonal. Silica particles have aroused exceptional deliberation in bio-analysis due to great progress in particular arenas, for instance, biocompatibility, unique properties of modifiable pore size and organization, huge facade areas and pore volumes, manageable morphology and amendable surfaces, elevated chemical and thermal stability. Currently, silica nanoparticles participate in crucial utilities in daily trade rationales such as power storage, chemical and genetic sensors, groceries dispensation and catalysis. Herein, the size-dependent interfacial relation of anionic silica nanoparticles with twelve altered categories of cationic surfactants has been carried out in terms of the physical chemical facets of colloid and interface science. The current analysis endeavours to investigate the virtual consequences of different surfactants through the development of the objective composite materials. The nanoparticle size controls, the surface-to-volume ratio and surface bend relating to its interaction with surfactant will also be addressed in this work. More importantly, the simulated stratagem developed in this work can be lengthened to formulate core-shell nanostructures with functional nanoparticles encapsulated in silica particles, making this approach valuable and extensively pertinent for employing sophisticated materials for catalysis and drug delivery.

Antidepressant Use Before and After the Diagnosis of Type 2 Diabetes

PubMed Central

Kivimäki, Mika; Tabák, Adam G.; Lawlor, Debbie A.; Batty, G. David; Singh-Manoux, Archana; Jokela, Markus; Virtanen, Marianna; Salo, Paula; Oksanen, Tuula; Pentti, Jaana; Witte, Daniel R.; Vahtera, Jussi

2010-01-01

OBJECTIVE To examine antidepressant use before and after the diagnosis of diabetes. RESEARCH DESIGN AND METHODS This study was a longitudinal analysis of diabetic and nondiabetic groups selected from a prospective cohort study of 151,618 men and women in Finland (the Finnish Public Sector Study, 1995–2005). We analyzed the use of antidepressants in those 493 individuals who developed type 2 diabetes and their 2,450 matched nondiabetic control subjects for each year during a period covering 4 years before and 4 years after the diagnosis. For comparison, we undertook a corresponding analysis on 748 individuals who developed cancer and their 3,730 matched control subjects. RESULTS In multilevel longitudinal models, the odds ratio for antidepressant use in those who developed diabetes was 2.00 (95% CI 1.57–2.55) times greater than that in nondiabetic subjects. The relative difference in antidepressant use between these groups was similar before and after the diabetes diagnosis except for a temporary peak in antidepressant use at the year of the diagnosis (OR 2.66 [95% CI 1.94–3.65]). In incident cancer case subjects, antidepressant use substantially increased after the cancer diagnosis, demonstrating that our analysis was sensitive for detecting long-term changes in antidepressant trajectories when they existed. CONCLUSIONS Awareness of the diagnosis of type 2 diabetes may temporarily increase the risk of depressive symptoms. Further research is needed to determine whether more prevalent use of antidepressants noted before the diagnosis of diabetes relates to effects of depression, side effects of antidepressant use, or a common causal pathway for depression and diabetes. PMID:20368411

Antidepressants and Weight Gain

MedlinePlus

... 2015;37:46. Blumenthal SR, et al. An electronic health records study of long-term weight gain following antidepressant ... your agreement to the Terms and Conditions and Privacy Policy linked below. Terms and Conditions Privacy Policy ...

Utilization of psychiatric care and antidepressants among people with different severity of depression: a population-based cohort study in Stockholm, Sweden.

PubMed

Sun, Yuying; Möller, Jette; Lundin, Andreas; Wong, Samuel Y S; Yip, Benjamin H K; Forsell, Yvonne

2018-06-01

To identify how severity of depression predicts future utilization of psychiatric care and antidepressants. Data derived from a longitudinal population-based study in Stockholm, Sweden, include 10443 participants aged 20-64 years. Depression was assessed by Major Depression Inventory and divided into subsyndromal, mild, moderate and severe depression. Outcomes were the first time of hospitalization, specialized outpatient care and prescribed drugs obtained from national register records. The association between severity of depression and outcomes was tested by Cox regression analysis, after adjusting for gender, psychiatric treatment history and socio-environmental factors. The cumulative incidences of hospitalizations, outpatient care and antidepressants were 4.0, 11.2, and 21.9% respectively. Compared to the non-depressed group, people with different severity of depression (subsyndromal, mild, moderate and severe depression) all had significantly higher risk of all three psychiatric services (all log-rank test P < 0.001). Use of psychiatric care and antidepressants increased by rising severity of depression. Although the associations between severity of depression and psychiatric services were significant, the dose relationship was not present in people with previous psychiatric history or after adjusting for gender and other factors. People with subsyndromal to severe depression all have increased future psychiatric service utilization compared to non-depressed people.

Human service work, gender and antidepressant use: a nationwide register-based 19-year follow-up of 752 683 women and men.

PubMed

Buscariolli, André; Kouvonen, Anne; Kokkinen, Lauri; Halonen, Jaana I; Koskinen, Aki; Väänänen, Ari

2018-06-01

To examine antidepressant use among male and female human service professionals. A random sample of individuals between 25 years and 54 years of age (n=752 683; 49.2% women; mean age 39.5 years). Information about each individual's filled antidepressant prescriptions from 1995 to 2014 was provided by the Social Insurance Institution. First, antidepressant use in five broad human service categories was compared with that in all other occupations grouped together, separately for men and women. Then, each of the 15 human service professions were compared with all other occupations from the same skill/education level (excluding other human services professions). Cox models were applied and the results are presented as HRs for antidepressant use with 95% CIs. The hazard of antidepressant use was higher among men working in human service versus all other occupations with the same skill/occupational level (1.22, 95% CI 1.18 to 1.27), but this was not the case for women (0.99, 95% CI 0.98 to 1.01). The risks differed between professions: male health and social care professionals (including medical doctors, nurses, practical nurses and home care assistants), social workers, childcare workers, teachers and psychologists had a higher risk of antidepressant use than men in non-human service occupations, whereas customer clerks had a lower risk. Male human service professionals had a higher risk of antidepressant use than men working in non-human service occupations. Gendered sociocultural norms and values related to specific occupations as well as occupational selection may be the cause of the elevated risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Research design features and patient characteristics associated with the outcome of antidepressant clinical trials.

PubMed

Khan, Arif; Kolts, Russell L; Thase, Michael E; Krishnan, K Ranga Rama; Brown, Walter

2004-11-01

The authors examined which, if any, research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials. Clinical trial data were reviewed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000. From the antidepressant research programs on these medications, 52 clinical trials were included in the study. The authors evaluated trial design features, patient characteristics, and difference in response between placebo and antidepressant. Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants. The severity of depressive symptoms before patient randomization, the dosing schedule (flexible versus fixed), the number of treatment arms, and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo. The duration of the antidepressant trial, number of patients per treatment arm, number of sites, and mean age of the patients were similar in successful trials (with a greater antidepressant-placebo difference) and less successful trials (with a smaller antidepressant-placebo difference). These findings may help in the design of future antidepressant trials.

Psychiatric and Psychological Factors in Patient Decision Making Concerning Antidepressant Use

ERIC Educational Resources Information Center

Dijkstra, Arie; Jaspers, Merlijne; van Zwieten, Marianne

2008-01-01

The observation that the use of antidepressants has strongly increased during the past decade implies that on a micro level doctors and patients more often decide that antidepressants are the appropriate treatment. Therefore, it is important to increase insight into patients' decision making regarding the use of antidepressants. The decision…

Suicidality and antidepressants in the elderly

PubMed Central

2008-01-01

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

Online social network response to studies on antidepressant use in pregnancy.

PubMed

Vigod, Simone N; Bagheri, Ebrahim; Zarrinkalam, Fattane; Brown, Hilary K; Mamdani, Muhammad; Ray, Joel G

2018-03-01

About 8% of U.S women are prescribed antidepressant medications around the time of pregnancy. Decisions about medication use in pregnancy can be swayed by the opinion of family, friends and online media, sometimes beyond the advice offered by healthcare providers. Exploration of the online social network response to research on antidepressant use in pregnancy could provide insight about how to optimize decision-making in this complex area. For all 17 research articles published on the safety of antidepressant use in pregnancy in 2012, we sought to explore online social network activity regarding antidepressant use in pregnancy, via Twitter, in the 48h after a study was published, compared to the social network activity in the same period 1week prior to each article's publication. Online social network activity about antidepressants in pregnancy quickly doubled upon study publication. The increased activity was driven by studies demonstrating harm associated with antidepressants, lower-quality studies, and studies where abstracts presented relative versus absolute risks. These findings support a call for leadership from medical journals to consider how to best incentivize and support a balanced and clear translation of knowledge around antidepressant safety in pregnancy to their readership and the public. Copyright © 2018 Elsevier Inc. All rights reserved.

Prevalence and patterns of antidepressant switching amongst primary care patients in the UK.

PubMed

Mars, Becky; Heron, Jon; Gunnell, David; Martin, Richard M; Thomas, Kyla H; Kessler, David

2017-05-01

Non-response to antidepressant treatment is a substantial problem in primary care, and many patients with depression require additional second-line treatments. This study aimed to examine the prevalence and patterns of antidepressant switching in the UK, and identify associated demographic and clinical factors. Cohort analysis of antidepressant prescribing data from the Clinical Practice Research Datalink, a large, anonymised UK primary care database. The sample included 262,844 patients who initiated antidepressant therapy between 1 January 2005 and 31 June 2011. 9.3% of patients switched to a different antidepressant product, with most switches (60%) occurring within 8 weeks of the index date. The proportion switching was similar for selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants (9.3%, 9.8% and 9.2%, respectively). Most switches were to an SSRI (64.5%), and this was the preferred option regardless of initial antidepressant class. Factors predictive of switching included male gender, age, and history of self-harm and psychiatric illness. Over one in every 11 patients who initiates antidepressant therapy will switch medication, suggesting that initial antidepressant treatment has been unsatisfactory. Evidence to guide choice of second-line treatment for individual patients is currently limited. Additional research comparing different pharmacological and psychological second-line treatment strategies is required in order to inform guidelines and improve patient outcomes.

Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication

PubMed Central

Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Díaz, Alvaro; Castro, Elena; dos Anjos, Severiano; Pascual-Brazo, Jesús; Linge, Raquel; Vargas, Veronica; Blanco, Helena; Martínez-Villayandre, Beatriz; Pazos, Ángel; Valdizán, Elsa M.

2013-01-01

It is widely accepted that changes underlying depression and antidepressant-like effects involve not only alterations in the levels of neurotransmitters as monoamines and their receptors in the brain, but also structural and functional changes far beyond. During the last two decades, emerging theories are providing new explanations about the neurobiology of depression and the mechanism of action of antidepressant strategies based on cellular changes at the CNS level. The neurotrophic/plasticity hypothesis of depression, proposed more than a decade ago, is now supported by multiple basic and clinical studies focused on the role of intracellular-signalling cascades that govern neural proliferation and plasticity. Herein, we review the state-of-the-art of the changes in these signalling pathways which appear to underlie both depressive disorders and antidepressant actions. We will especially focus on the hippocampal cellularity and plasticity modulation by serotonin, trophic factors as brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) through intracellular signalling pathways—cAMP, Wnt/β-catenin, and mTOR. Connecting the classic monoaminergic hypothesis with proliferation/neuroplasticity-related evidence is an appealing and comprehensive attempt for improving our knowledge about the neurobiological events leading to depression and associated to antidepressant therapies. PMID:23862076

Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis.

PubMed

Mehta, Swati; Guy, Stacey; Lam, Tracey; Teasell, Robert; Loh, Eldon

2015-01-01

To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI). A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with ≥ 3 individuals and ≥ 50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen's d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted. Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 ± 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group. The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required.

Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

PubMed

Postuma, Ronald B; Gagnon, Jean-Francois; Tuineaig, Maria; Bertrand, Josie-Anne; Latreille, Veronique; Desjardins, Catherine; Montplaisir, Jacques Y

2013-11-01

Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. Prospective cohort study. Tertiary sleep disorders center. 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.

Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort.

PubMed

Arbus, Christophe; Gardette, Virginie; Bui, Eric; Cantet, Christelle; Andrieu, Sandrine; Nourhashémi, Fati; Schmitt, Laurent; Vellas, Bruno

2010-02-01

Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription. REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI). A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression. The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

Treatment of Fibromyalgia with Antidepressants

PubMed Central

O'Malley, Patrick G; Balden, Erin; Tomkins, Glen; Santoro, James; Kroenke, Kurt; Jackson, Jeffrey L

2000-01-01

BACKGROUND Fibromyalgia is a common, poorly understood musculoskeletal pain syndrome with limited therapeutic options. OBJECTIVE To systematically review the efficacy of antidepressants in the treatment of fibromyalgia and examine whether this effect was independent of depression. DESIGN Meta-analysis of English-language, randomized, placebo-controlled trials. Studies were obtained from searching medline, embase, and psyclit(1966-1999), the Cochrane Library, unpublished literature, and bibliographies. We performed independent duplicate review of each study for both inclusion and data extraction. MAIN RESULTS Sixteen randomized, placebo-controlled trials were identified, of which 13 were appropriate for data extraction. There were 3 classes of antidepressants evaluated: tricyclics (9 trials), selective serotonin reuptake inhibitors (3 trials), and S-adenosylmethionine (2 trials). Overall, the quality of the studies was good (mean score 5.6, scale 0-8). The odds ratio for improvement with therapy was 4.2 (95% confidence interval [95% CI], 2.6 to 6.8). The pooled risk difference for these studies was 0.25 (95% CI, 0.16 to 0.34), which calculates to 4 (95% CI, 2.9 to 6.3) individuals needing treatment for 1 patient to experience symptom improvement. When the effect on individual symptoms was combined, antidepressants improved sleep, fatigue, pain, and well-being, but not trigger points. In the 5 studies where there was adequate assessment for an effect independent of depression, only 1 study found a correlation between symptom improvement and depression scores. Outcomes were not affected by class of agent or quality score using meta-regression. CONCLUSION Antidepressants are efficacious in treating many of the symptoms of fibromyalgia. Patients were more than 4 times as likely to report overall improvement, and reported moderate reductions in individual symptoms, particularly pain. Whether this effect is independent of depression needs further study. PMID:11029681

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants' Efficacy and Harm.

PubMed

Hengartner, Michael P

2017-01-01

In current psychiatric practice, antidepressants are widely and with ever-increasing frequency prescribed to patients. However, several scientific biases obfuscate estimates of antidepressants' efficacy and harm, and these are barely recognized in treatment guidelines. The aim of this mini-review is to critically evaluate the efficacy and harm of antidepressants for acute and maintenance treatment with respect to systematic biases related to industry funding and trial methodology. Narrative review based on a comprehensive search of the literature. It is shown that the pooled efficacy of antidepressants is weak and below the threshold of a minimally clinically important change once publication and reporting biases are considered. Moreover, the small mean difference in symptom reductions relative to placebo is possibly attributable to observer effects in unblinded assessors and patient expectancies. With respect to trial dropout rates, a hard outcome not subjected to observer bias, no difference was observed between antidepressants and placebo. The discontinuation trials on the efficacy of antidepressants in maintenance therapy are systematically flawed, because in these studies, spontaneous remitters are excluded, whereas half of all patients who remitted on antidepressants are abruptly switched to placebo. This can cause a severe withdrawal syndrome that is easily misdiagnosed as a relapse when assessed on subjective symptom rating scales. In accordance, the findings of naturalistic long-term studies suggest that maintenance therapy has no clear benefit, and non-drug users do not show increased recurrence rates. Moreover, a growing body of evidence from hundreds of randomized controlled trials suggests that antidepressants cause suicidality, but this risk is underestimated because data from industry-funded trials are systematically flawed. Unselected, population-wide observational studies indicate that depressive patients who use antidepressants are at an increased

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

PubMed

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

2016-09-01

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

Antidepressant Utilization and Suicide in Europe: An Ecological Multi-National Study

PubMed Central

Gusmão, Ricardo; Quintão, Sónia; McDaid, David; Arensman, Ella; Van Audenhove, Chantal; Coffey, Claire; Värnik, Airi; Värnik, Peeter; Coyne, James; Hegerl, Ulrich

2013-01-01

Background Research concerning the association between use of antidepressants and incidence of suicide has yielded inconsistent results and is the subject of considerable controversy. The first aim is to describe trends in the use of antidepressants and rates of suicide in Europe, adjusted for gross domestic product, alcohol consumption, unemployment, and divorce. The second aim is to explore if any observed reduction in the rate of suicide in different European countries preceded the trend for increased use of antidepressants. Methods Data were obtained for 29 European countries between 1980 and 2009. Pearson correlations were used to explore the direction and magnitude of associations. Generalized linear mixed models and Poisson regression distribution were used to clarify the effects of antidepressants on suicide rates, while an autoregressive adjusted model was used to test the interaction between antidepressant utilization and suicide over two time periods: 1980–1994 and 1995–2009. Findings An inverse correlation was observed in all countries between recorded Standardised Death Rate (SDR) for suicide and antidepressant Defined Daily Dosage (DDD), with the exception of Portugal. Variability was marked in the association between suicide and alcohol, unemployment and divorce, with countries depicting either a positive or a negative correlation with the SDR for suicide. Every unit increase in DDD of an antidepressant per 1000 people per day, adjusted for these confounding factors, reduces the SDR by 0.088. The correlation between DDD and suicide related SDR was negative in both time periods considered, albeit more pronounced between 1980 and 1994. Conclusions Suicide rates have tended to decrease more in European countries where there has been a greater increase in the use of antidepressants. These findings underline the importance of the appropriate use of antidepressants as part of routine care for people diagnosed with depression, therefore reducing the

Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

PubMed Central

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

2011-01-01

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

Misleading Advertising for Antidepressants in Sweden: A Failure of Pharmaceutical Industry Self-Regulation

PubMed Central

Zetterqvist, Anna V.; Mulinari, Shai

2013-01-01

Background The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. Methodology We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994–2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Principal Findings Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Conclusions Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system’s failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self

Mother-infant antidepressant concentrations, maternal depression, and perinatal events.

PubMed

Sit, Dorothy; Perel, James M; Wisniewski, Stephen R; Helsel, Joseph C; Luther, James F; Wisner, Katherine L

2011-07-01

The authors explored the relationship of cord-maternal antidepressant concentration ratios and maternal depression with perinatal events and preterm birth. The investigators examined 21 mother-infant pairs that had antidepressant exposure during pregnancy. The antidepressants included serotonin reuptake inhibitors (SRIs) and nortriptyline (a norepinephrine inhibitor and mild SRI). The mothers were evaluated with the Structured Clinical Interview for DSM-IV. Depression ratings were repeated at 20, 30, and 36 weeks' pregnancy. At delivery, investigators assessed cord and maternal antidepressant concentrations, neonatal outcomes on the Peripartum Events Scale (PES), and gestational weeks at birth. The investigators performed this study at the Women's Behavioral HealthCARE Program, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pennsylvania, from April 2003 until September 2006. Mean ± SD cord-to-maternal concentration ratios were 0.52 ± 0.35 (range, 0.00-1.64) for the parent drug and 0.54 ± 0.17 (range, 0.28-0.79) for the metabolite. Nine of 21 mothers (43%) had a major depressive episode. From examining the maximum depression ratings, the mean ± SD Structured Interview Guide for the Hamilton Depression Rating Scale, Atypical Depression Symptoms Version score was 16.0 ± 7.6. One third (7/21) of infants had at least 1 perinatal event (PES ≥ 1). The frequency of deliveries complicated by any perinatal event was similar in depressed and nondepressed mothers. There was no significant association between perinatal events and cord-to-maternal antidepressant concentration ratios or maternal depression levels. Exposure to short half-life antidepressants compared to fluoxetine resulted in more perinatal events (7/16 = 44% vs 0/5 = 0%; P = .06). Fourteen percent (3/21) of infants were preterm. Preterm birth was not associated with cord-to-maternal metabolite concentration ratios, depression levels, or exposure to fluoxetine

Antidepressant treatment of depression in rural nursing home residents.

PubMed

Kerber, Cindy Sullivan; Dyck, Mary J; Culp, Kennith R; Buckwalter, Kathleen

2008-09-01

Under-diagnosis and under-treatment of depression are major problems in nursing home residents. The purpose of this study was to determine antidepressant use among nursing home residents who were diagnosed with depression using three different methods: (1) the Geriatric Depression Scale, (2) Minimum Data Set, and (3) primary care provider assessments. As one would expect, the odds of being treated with an antidepressant were about eight times higher for those diagnosed as depressed by the primary care provider compared to the Geriatric Depression Scale or the Minimum Data Set. Men were less likely to be diagnosed and treated with antidepressants by their primary care provider than women. Depression detected by nurses through the Minimum Data Set was treated at a lower rate with antidepressants, which generates issues related to interprofessional communication, nursing staff communication, and the need for geropsychiatric role models in nursing homes.

Antidepressants and REM Sleep Behavior Disorder: Isolated Side Effect or Neurodegenerative Signal?

PubMed Central

Postuma, Ronald B.; Gagnon, Jean-Francois; Tuineaig, Maria; Bertrand, Josie-Anne; Latreille, Veronique; Desjardins, Catherine; Montplaisir, Jacques Y.

2013-01-01

Objectives: Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. Design: Prospective cohort study. Setting: Tertiary sleep disorders center. Participants: 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. Measurements/Results: Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). Conclusions: Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with “purely-idiopathic” RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative

Mirtazapine versus other antidepressive agents for depression

PubMed Central

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

2014-01-01

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

Mirtazapine versus other antidepressive agents for depression.

PubMed

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

2011-12-07

Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice. The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis review group's specialised register (CCDANCTR), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to April 2011), EMBASE, (1980 to July 2011) MEDLINE (1950 to July 2011) and PsycINFO (1974 to July 2011). Reference lists of the reports of relevant studies were checked and experts in the field contacted. The review was not limited to English-language articles. Randomised controlled trials (RCTs) allocating participants with major depression to mirtazapine versus any other antidepressive agent. Two authors independently checked eligibility and extracted data on an intention-to-treat basis. The primary outcome was response to treatment. The secondary outcomes included dropouts and individual adverse events.Meta-analyses were conducted using the random-effects model. A total of 29 RCTs (n = 4974), mostly following up the participants for six weeks in outpatient clinics and inadequately reporting the risk of bias, were included. In comparison with tricyclic antidepressants (10 trials, n = 1553) there was no robust evidence to detect a difference between mirtazapine and tricyclics in terms of response at two weeks (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.64 to 1.13) or at the end of acute-phase treatment (at 6 to 12 weeks) (OR 0.89, 95% CI 0.72 to 1.10). In comparison with selective serotonin reuptake inhibitors (SSRIs) (12 trials, n = 2626) mirtazapine was significantly more effective at two weeks (OR 1.57, 95% CI 1.30 to 1.88) and at the end of acute-phase treatment (OR 1

Age-Related Response to Redeemed Antidepressants Measured by Completed Suicide in Older Adults: A Nationwide Cohort Study

PubMed Central

Erlangsen, Annette; Conwell, Yeates

2013-01-01

Objective To examine if the suicide rate of older adults prescribed antidepressants varies with age and to assess the proportion of older adults who died by suicide that had recently been prescribed antidepressants. Methods A population-based cohort study using a nationwide linkage of individual-level records was conducted on all persons aged 50+ living in Denmark during 1996–2006 (1,215,524 men and 1,343,568 women). Suicide rates by treatment status were calculated using data on all antidepressant prescriptions redeemed at pharmacies. Results Individual-level data covered 9,354,620 and 10,720,639 person-years for men and women, respectively. Men aged 50–59 who received antidepressants had a mean suicide rate of 185 (95% confidence interval [CI]: 160–211) per 100,000, whereas for those aged 80+ the rate was 119 (95% CI: 91–146). For women, the corresponding values were 82 (95% CI: 70–94) and 28 (95% CI: 20–35). Logistic regression showed a 2% and 3% decline in the rate for men and women, respectively, considered in treatment with antidepressants, with each additional year of age. An opposite trend was found for persons not in treatment. Fewer persons aged 80+ dying by suicide had received antidepressant prescriptions during the last months of life than younger persons. Conclusion An age-dependent decline in suicide rate for antidepressant recipients was identified. One reason could be that older adults respond better to antidepressants than younger age groups. Still, the increasing gap with age between estimated prevalence of depression and antidepressant prescription rate in persons dying by suicide underscores the need for assessment of depression in the oldest old. PMID:23567434

[The pharmacological basis of the serotonin system: Application to antidepressant response].

PubMed

David, D J; Gardier, A M

2016-06-01

If serotonin (5-hydroxytryptamin [5-HT]) is well known for its role in mood regulation, it also impacts numerous physiological functions at periphery. Serotonin is synthetized at the periphery into the gut by intestinal enterochromaffin cells and in the central nervous system (CNS) in the raphe nucleus from the essential amino acid tryptophan. Physiological effects of 5-HT are mediated by about 15 serotoninergic receptors grouped into seven broad families (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7 receptor families). Except 5-HT3 receptor, a ligand-gated ion channels, all the others are G protein-coupled receptors. Serotonin's homeostasis involves serotoninergic autoreceptor such as 5-HT1A, 5-HT1B, 5-HT1D, the enzymatic degradation of serotonin by monoamine oxidase A (MAO-A), and a transporter (serotoninergic transporter [SERT]). In the CNS, the SERT is a key target for various antidepressant drugs such as Selective Serotonin Reuptake Inhibitors (SSRI), Serotonin Norepinephrin Reuptake Inhibitors (SNRI) and tricyclics family. However, antidepressant activity of SERT inhibitors is not directly mediated by the SERT inhibition, but a consequence of postsynaptic 5-HT receptor activation following the increase in 5-HT levels in the synaptic cleft. In pharmacology, SSRIs are defined as indirect agonist of postsynaptic receptor. Among all the 5-HT receptors, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2B and 5-HT4 receptors activation would mediate antidepressant effects. In the meanwhile, 5-HT2A, 5-HT2C, 5-HT3, 5-HT6 and 5-HT7 receptors activation would induce opposite effects. The best serotoninergic antidepressant would directly activate 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2B and 5-HT4 and would block 5-HT2A, 5-HT2C, 5-HT3, 5-HT6 and 5-HT7 receptor. If the chemical synthesis of such a compound may be compromised, SERT inhibition associated with the blockade of some but not all 5-HT receptor could shorten onset of action and/or improve antidepressant efficacy on the overall

Fluvoxamine versus other anti-depressive agents for depression

PubMed Central

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

2014-01-01

with regard to gastrointestinal side effects of fluvoxamine when compared to other antidepressants. For example, fluvoxamine was generally associated with a higher incidence of vomiting/nausea (versus imipramine, OR 2.23, CI 1.59 to 3.14; versus clomipramine, OR 2.13, CI 1.06 to 4.27; versus amitriptyline, OR 2.86, CI 1.31 to 2.63). Authors’ conclusions We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles. PMID:20238342

Gender display in Scandinavian and American advertising for antidepressants.

PubMed

Lövdahl, U; Riska, A; Riska, E

1999-12-01

This study examines whether depiction of users of antidepressants in advertisements for antidepressants in the 1995 issues of the major medical journal in each of Denmark, Finland, Norway, and Sweden differs from that in the American Journal of Psychiatry. The results show that the people shown in the Danish, Finnish, and Norwegian journals are predominantly women, whereas depiction of users in the American and Swedish advertising is predominantly of couples. The portrayals in the 1995 advertising are of antidepressants as female gendered; a feature that was not seen in advertising for psychotropic drugs in the Nordic countries in the 1980s.

Harmane induces anxiolysis and antidepressant-like effects in rats.

PubMed

Aricioglu, Feyza; Altunbas, Hale

2003-12-01

A forced swim test (FST) and an elevated plus maze (EPM) were used to determine antidepressant and anxiolytic effects of harmane in rats in comparison with a known antidepressant, imipramine (30 mg/kg i.p.). Harmane (2.5, 5.0, or 10 mg/kg, i.p.), saline, or imipramine were given 30 minutes before the tests. Administration of harmane decreased the time of immobility in the FST dose-dependently and increased the time spent in open arms in the EPM, as compared with the saline group. As an endogenous substance, harmane therefore has anti-anxiety and antidepressant effects.

Citalopram versus other anti-depressive agents for depression

PubMed Central

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

2014-01-01

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

Appropriateness of antidepressant prescribing: an observational study in a Scottish primary-care setting.

PubMed

Cameron, Isobel M; Lawton, Kenneth; Reid, Ian C

2009-09-01

Since the 1990s, Scottish community-based antidepressant prescribing has increased substantially. To assess whether GPs prescribe antidepressants appropriately. Observational study of adults (aged >/=16 years) screened with the Hospital Anxiety and Depression Scale (HADS) attending a GP. Four practices in Grampian, Scotland. Patients (n = 898) completed the HADS, and GPs independently estimated depression status. Notes were scrutinised for evidence of antidepressant use, and the appropriateness of prescribing was assessed. A total of 237 (26%) participants had HADS scores indicating 'possible' (15%) or 'probable' (11%) depression. The proportion of participants rated as depressed by their GP differed significantly by HADS depression subscale scores. Odds ratio for 'possible' versus 'no' depression was 3.54 (95% confidence interval [CI] = 2.17 to 5.76, P<0.001); and for 'probable' versus 'possible' depression was 3.59 (95% CI = 2.06 to 6.26, P<0.001). Similarly, the proportion of participants receiving antidepressants differed significantly by HADS score. Odds ratio for 'possible' versus 'no' depression was 2.79 (95% CI = 1.70 to 4.58, P<0.001); and for 'probable' versus 'possible' was 2.12 (95% CI = 1.21 to 3.70, P = 0.009). In 101 participants with 'probable' depression, GPs recognised 53 (52%) participants as having a clinically significant depression. Inappropriate initiation of antidepressant treatment occurred very infrequently. Prescribing to participants who were not symptomatic was accounted for by the treatment of pain, anxiety, or relapse prevention, and for ongoing treatment of previously identified depression. There was little evidence of prescribing without relevant indication. Around half of patients with significant symptoms were not identified by their GP as suffering from a depressive disorder: this varied inversely with severity ratings. Rather than prescribing indiscriminately (as has been widely assumed), it is likely that GPs are initiating

Feasibility of nurse-led antidepressant medication management of depression in an HIV clinic in Tanzania.

PubMed

Adams, Julie L; Almond, Maria L G; Ringo, Edward J; Shangali, Wahida H; Sikkema, Kathleen J

2012-01-01

Sub-Saharan Africa has the highest HIV prevalence worldwide and depression is highly prevalent among those infected. The negative impact of depression on HIV outcomes highlights the need to identify and treat it in this population. A model for doing this in lower-resourced settings involves task-shifting depression treatment to primary care; however, HIV-infected individuals are often treated in a parallel HIV specialty setting. We adapted a model of task-shifting, measurement-based care (MBC), for an HIV clinic setting and tested its feasibility in Tanzania. MBC involves measuring depressive symptoms at meaningful intervals and adjusting antidepressant medication treatment based on the measure of illness. Twenty adults presenting for care at an outpatient HIV clinic in Tanzania were enrolled and followed by a nurse care manager who measured depressive symptoms at baseline and every 4 weeks for 12 weeks. An algorithm-based decision-support tool was utilized by the care manager to recommend individualized antidepressant medication doses to participants' HIV providers at each visit. Retention was high and fidelity of the care manager to the MBC protocol was exceptional. Follow through of antidepressant prescription dosing recommendations by the prescriber was low. Limited availability of antidepressants was also noted. Despite challenges, baseline depression scores decreased over the 12-week period. Overall, the model of algorithm-based nursing support of prescription decisions was feasible. Future studies should address implementation issues of medication supply and dosing. Further task-shifting to relatively more abundant and lower-skilled health workers, such as nurses' aides, warrants examination.

Risk of injurious road traffic crash after prescription of antidepressants.

PubMed

Orriols, Ludivine; Queinec, Raphaëlle; Philip, Pierre; Gadegbeku, Blandine; Delorme, Bernard; Moore, Nicholas; Suissa, Samy; Lagarde, Emmanuel

2012-08-01

To estimate the risk of road traffic crash associated with prescription of antidepressants. Data were extracted and matched from 3 French national databases: the national health care insurance database, police reports, and the national police database of injurious crashes. A case-control analysis comparing 34,896 responsible versus 37,789 nonresponsible drivers was conducted. Case-crossover analysis was performed to investigate the acute effect of medicine exposure. 72,685 drivers, identified by their national health care number, involved in an injurious crash in France from July 2005 to May 2008 were included. 2,936 drivers (4.0%) were exposed to at least 1 antidepressant on the day of the crash. The results showed a significant association between the risk of being responsible for a crash and prescription of antidepressants (odds ratio [OR] = 1.34; 95% CI, 1.22-1.47). The case-crossover analysis showed no association with treatment prescription, but the risk of road traffic crash increased after an initiation of antidepressant treatment (OR = 1.49; 95% CI, 1.24-1.79) and after a change in antidepressant treatment (OR = 1.32; 95% CI, 1.09-1.60). Patients and prescribers should be warned about the risk of crash during periods of treatment with antidepressant medication and about particularly high vulnerability periods such as those when a treatment is initiated or modified. © Copyright 2012 Physicians Postgraduate Press, Inc.

Abnormalities of P300 before and after antidepressant treatment in depression: an ERP-sLORETA study.

PubMed

Zhou, Lina; Wang, Gaohua; Wang, Huiling

2018-02-07

Despite a wide range of reports on depression-induced P300 changes, it is still debatable whether P300 can return to a pattern characteristic of healthy individuals following antidepressant treatment. Thus, the present study aims to compare P300 and its underlying neural activation in depressed patients before and after antidepressant treatment to explore the brain regions related to pathogenesis and to evaluate the prognosis after treatment. P300 was evoked by the oddball auditory paradigm and collected from 14 sex-matched, age-matched, and education level-matched patients and controls. P300 was also collected in the same patients after treatment. sLORETA was used to explore the source activation of P300 components. Depressed patients before and after antidepressant treatment tended to show lower P300 amplitudes compared with healthy controls, and their P300 amplitudes of F3 electrodes were correlated negatively to their scores on the 24-item Hamilton Depression Rating Scale, the Snaith-Hamilton Pleasure Scale, and the nine-item Patient Health Questionnaire. P300 amplitudes of P4 electrodes were correlated negatively with their scores on the Dysfunctional Attitude Scale. P300 source activation of depressed patients before antidepressant treatment was reduced in the left superior parietal lobule and the precuneus compared with healthy controls and depressed patients after treatment. No difference was found between healthy controls and depressed patients after treatment. The left superior parietal lobule and the precuneus might be therapeutic targets of depression.

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

PubMed Central

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

Antidepressant Drug Treatment in Association with Multiple Sclerosis Disease-Modifying Therapy: Using Explorys in the MS Population.

PubMed

Mirsky, Matthew M; Marrie, Ruth Ann; Rae-Grant, Alexander

2016-01-01

Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: "Power searches" were built to test the relationship between antidepressant drug use and DMT in the MS population. Searches were built to produce a cohort of individuals diagnosed as having MS in the past 3 years taking a specific DMT who were then given any antidepressant drug. The antidepressant drug therapy prevalence was tested in the MS population on the following DMTs: IFNβ-1a, IFNβ-1b, combined IFNβ, glatiramer acetate, natalizumab, fingolimod, and dimethyl fumarate. Results: In patients with MS, the rate of antidepressant drug use in those receiving DMTs was 40.60% to 44.57%. The rate of antidepressant drug use for combined IFNβ DMTs was 41.61% (males: 31.25%-39.62%; females: 43.10%-47.33%). Antidepressant drug use peaked in the group aged 45 to 54 years for five of six DMTs. Conclusions: We found no association between IFNβ treatment and antidepressant drug use in the MS population compared with other DMTs. The EPM database has been validated against the Patten et al. data for future use in the MS population.

Thyroid-stimulating hormone, 5-HTTLPR genotype, and antidepressant response in depressed women.

PubMed

Gressier, Florence; Trabado, Séverine; Verstuyft, Céline; Bouaziz, Elodie; Hardy, Patrick; Fève, Bruno; Becquemont, Laurent; Corruble, Emmanuelle

2011-10-01

Basal serum thyroid-stimulating hormone (TSH) levels may predict antidepressant efficacy in patients with major depressive episodes (MDE), but data are inconsistent. As the SS genotype of the 5-HTTLPR polymorphism has been associated with a lower antidepressant efficacy in women with MDE, we aimed at assessing the relationship between normal basal TSH, 5-HTTLPR, and antidepressant efficacy in women. A total of 71 women and 28 men, with normal baseline TSH serum levels, hospitalized for a MDE, were assessed for 5-HTTLPR genotypes and prospectively followed for short-term antidepressant efficacy. Women with SS genotype had higher TSH levels (P=0.002) and a worse antidepressant response (P=0.046) than the women with LL/LS genotype, whereas no significant difference was shown in men. In multivariate analyses, antidepressant response in women was explained by TSH and 5-HTTLPR, but not by other variables. Further research is needed to understand the underlying mechanism explaining interactions between sex, TSH, and serotonergic function.

Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling.

PubMed

Neis, Vivian Binder; Moretti, Morgana; Bettio, Luis Eduardo B; Ribeiro, Camille M; Rosa, Priscila Batista; Gonçalves, Filipe Marques; Lopes, Mark William; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

2016-06-01

The activation of AMPA receptors and mTOR signaling has been reported as mechanisms underlying the antidepressant effects of fast-acting agents, specially the NMDA receptor antagonist ketamine. In the present study, oral administration of agmatine (0.1mg/kg), a neuromodulator that has been reported to modulate NMDA receptors, caused a significant reduction in the immobility time of mice submitted to the tail suspension test (TST), an effect prevented by the administration of DNQX (AMPA receptor antagonist, 2.5μg/site, i.c.v.), BDNF antibody (1μg/site, i.c.v.), K-252a (TrkB receptor antagonist, 1μg/site, i.c.v.), LY294002 (PI3K inhibitor, 10nmol/site, i.c.v.) or rapamycin (selective mTOR inhibitor, 0.2nmol/site, i.c.v.). Moreover, the administration of lithium chloride (non-selective GSK-3β inhibitor, 10mg/kg, p.o.) or AR-A014418 (selective GSK-3β inhibitor, 0.01μg/site, i.c.v.) in combination with a sub-effective dose of agmatine (0.0001mg/kg, p.o.) reduced the immobility time in the TST when compared with either drug alone. Furthermore, increased immunocontents of BDNF, PSD-95 and GluA1 were found in the prefrontal cortex of mice just 1h after agmatine administration. These results indicate that the antidepressant-like effect of agmatine in the TST may be dependent on the activation of AMPA and TrkB receptors, PI3K and mTOR signaling as well as inhibition of GSK-3β, and increase in synaptic proteins. The results contribute to elucidate the complex signaling pathways involved in the antidepressant effect of agmatine and reinforce the pivotal role of these molecular targets for antidepressant responses. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Pharmacology of 1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone, a novel antidepressant compound with antianxiety activity.

PubMed

Ellis, K O; Wessels, F L; Burns, R H; Pong, S F

1980-10-01

1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone (I) was evaluated in selected pharmacological tests, and its activity was compared to that of some clinically useful psychotropic drugs. Based on the results, it is evident that I has a unique profile of antidepressant and antianxiety activities that are evident in the same dose range. The mechanism of its antidepressant activity is proposed to be similar to the tricyclic antidepressants, that is, inhibition of norepinephrine uptake. Neither I nor the tricyclic antidepressants possess monoamine oxidase-inhibiting activity. However, unlike the tricyclic antidepressants, I is devoid of any significant anticholinergic activity and presumably is free of anticholinergic side effects.

Identification of the cortical neurons that mediate antidepressant responses

PubMed Central

Schmidt, Eric F.; Warner-Schmidt, Jennifer; Otopalik, Benjamin G.; Pickett, Sarah B.; Greengard, Paul; Heintz, Nathaniel

2012-01-01

Summary Our understanding of current treatments for depression, and the development of more specific therapies, is limited by the complexity of the circuits controlling mood and the distributed actions of antidepressants. Although the therapeutic efficacy of SSRIs is correlated with increases in cortical activity, the cell types crucial for their action remain unknown. Here we employ bacTRAP translational profiling to show that layer 5 corticostriatal pyramidal cells expressing p11 (S100a10) are strongly and specifically responsive to chronic antidepressant treatment. This response requires p11 and includes the specific induction of Htr4 expression. Cortex-specific deletion of p11 abolishes behavioral responses to SSRI’s, but does not lead to increased depression-like behaviors. Our data identify corticostriatal projection neurons as critical for the response to antidepressants, and suggest that the regulation of serotonergic tone in this single cell type plays a pivotal role in antidepressant therapy. PMID:22632977

Design of clinical trials of antidepressants: should a placebo control arm be included?

PubMed

Fritze, J; Möller, H J

2001-01-01

There is no doubt that available antidepressants are efficacious and effective. Nevertheless, more effective drugs with improved tolerability are needed. With this need in mind, some protagonists claim that future antidepressants should be proved superior to, or at least as effective as, established antidepressants, making placebo control methodologically dispensable in clinical trials. Moreover, the use of placebo control is criticised as unethical because it might result in effective treatment being withheld. There are, however, a number of methodological reasons why placebo control is indispensable for the proof of efficacy of antidepressants. Comparing investigational antidepressants only with standard antidepressants and not placebo yields ambiguous results that are difficult to interpret, be it in superiority or equivalence testing, and this method of assessment requires larger sample sizes than those required with the use of placebo control. Experimental methodology not adhering to the optimal study design is ethically questionable. Restricting the testing of investigational antidepressants only to superiority over standard antidepressants is an obstacle to therapeutic progress in terms of tolerability and the detection of innovative mechanisms of action from which certain subgroups of future patients might benefit. The use of a methodology that requires larger samples for testing of superiority or equivalence is also ethically questionable. In view of the high placebo response rates in trials of antidepressants, placebo treatment does not mean withholding effective treatment. Accepting the necessity of the clinical evaluation of new, potentially ineffective antidepressants implicitly means accepting placebo control as ethically justified. Three- or multi-arm comparisons including placebo and an active reference represent the optimal study design.

Neuronal plasticity and antidepressant actions

PubMed Central

Castrén, Eero; Hen, René

2013-01-01

Antidepressant treatments enhance plasticity and increase neurogenesis in the adult brain, but it has been unclear how these effects influence mood. We propose that like environmental enrichment and exercise, antidepressant treatments enhance adaptability by increasing structural variability within the nervous system at many levels, from proliferating precursors to immature synaptic contacts. Conversely, sensory deprivation and chronic stress reduce this structural variability. Activity-dependent competition within the mood-related circuits, guided by rehabilitation, then selects for the survival and stabilization of those structures that best represent the internal or external milieu. Increased variability together with competition-mediated selection facilitates normal function, such as pattern separation within the dentate gyrus and other mood-related circuits, thereby enhancing adaptability towards novel experiences. PMID:23380665

Antidepressant-Like Effect of Isorhynchophylline in Mice.

PubMed

Xian, Yan-Fang; Fan, Ding; Ip, Siu-Po; Mao, Qing-Qiu; Lin, Zhi-Xiu

2017-02-01

Isorhynchophylline (IRN), an oxindole alkaloid, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla (Miq) Miq ex Havil. (Rubiaceae). Previous studies in our laboratory have revealed that IRN possesses potent neuroprotective effects in different models of Alzheimer's disease. However, the antidepressant-like effects of IRN are remained unclear. The present study aims to evaluate the antidepressant-like effects of IRN. The antidepressant-like effects of IRN was determined by using animal models of depression including forced swimming and tail suspension tests. The acting mechanism was explored by determining the effect of IRN on the levels of monoamine neurotransmitters and the activities of monoamine oxidases. Intragastric administration of IRN at 10, 20 and 40 mg/kg for 7 days caused a significant reduction of immobility time in both forced swimming and tail suspension tests, while IRN did not stimulate locomotor activity in the open-field test. In addition, IRN treatment antagonized reserpine-induced ptosis and significantly enhanced the levels of monoamine neurotransmitters including norepinephrine (NE) and 5-hydroxytryptamine (5-HT), and the activity of monoamine oxidase A (MAO-A) in the hippocampus and frontal cortex of mice. These results suggest that the antidepressant-like effects of IRN are mediated, at least in part, by the inhibition of monoamine oxidases.

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.

Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

PubMed

Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping

2016-01-19

The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.

Factors associated with switching and combination use of antidepressants in young Swedish adults

PubMed Central

Andersson Sundell, K; Petzold, M G; Wallerstedt, S M

2013-01-01

Aims Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20–34 years. Methods Individuals, aged 20–34 years, who purchased an antidepressant in January–June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. Results A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93–2.57), and lower in individuals with high education: 0.64 (0.54–0.75), and shorter length of follow-up: 0.73 (0.62–0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05–2.49), and lower among individuals with short university education: 0.58 (0.43–0.78), those starting on mirtazapine: 0.78 (0.62–0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63–0.88). Conclusions One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase

Synthesis of 2,4-dihydroxychalcone derivatives as potential antidepressant effect.

PubMed

Guan, L-P; Zhao, D-H; Chang, Y; Wen, Z-S; Tang, L-M; Huang, F-F

2013-01-01

In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system. © Georg Thieme Verlag KG Stuttgart · New York.

Monoamine reuptake site occupancy of sibutramine: Relationship to antidepressant-like and thermogenic effects in rats.

PubMed

Li, Yu-Wen; Langdon, Shaun; Pieschl, Rick; Strong, Todd; Wright, Robert N; Rohrbach, Kenneth; Lelas, Snjezana; Lodge, Nicholas J

2014-08-15

Sibutramine was formerly marketed as an anti-obesity agent. The current study investigated the relationships between monoamine reuptake site occupancy for sibutramine and both its antidepressant-like efficacy and thermogenic effects. Sibutramine's effects on locomotor activity (LMA) and food intake were also evaluated. Sibutramine occupied monoamine reuptake binding sites with the rank order of potency of NET>SERT>DAT; at 10mg/kg, po, occupancy was 95% NET, 81% SERT and 73% DAT. Sibutramine produced antidepressant-like behavior in the forced swim test; at the lowest effective dose (3mg/kg, po) occupancy was 61%, 90% and 23% at SERT, NET and DAT sites, respectively. Sibutramine also increased body core temperature in a dose- and time-dependent manner; at the lowest effective dose (30mg/kg) SERT, NET and DAT occupancies were respectively 78%, 86% and 59%. A significant decrease in food consumption was observed at 3 and 10mg/kg, po. LMA was increased at ≥10mg/kg, sc. The relationship between efficacy in the FST and occupancy was also determined for citalopram, fluoxetine and reboxetine. Similarly, the relationship between thermogenesis and target occupancy for several single or double/triple reuptake inhibitors was measured and showed that >40-50% DAT binding was required for thermogenesis. Thermogenesis was blocked by the D1 antagonist SCH39166 (3mg/kg, sc). Our findings indicate that the antidepressant-like effect of sibutramine may result from additive or synergistic actions on the three reuptake binding targets. At higher doses, sibutramine produces thermogenesis; DAT inhibition and activation of dopamine D1 receptors are required for this effect. Published by Elsevier B.V.

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

PubMed

Fong, Peter P; Ford, Alex T

2014-06-01

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

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects.

PubMed

Sanacora, G; Smith, M A; Pathak, S; Su, H-L; Boeijinga, P H; McCarthy, D J; Quirk, M C

2014-09-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

Evaluation of antidepressant-like and anxiolytic-like activity of purinedione-derivatives with affinity for adenosine A2A receptors in mice.

PubMed

Dziubina, Anna; Szmyd, Karina; Zygmunt, Małgorzata; Sapa, Jacek; Dudek, Magdalena; Filipek, Barbara; Drabczyńska, Anna; Załuski, Michał; Pytka, Karolina; Kieć-Kononowicz, Katarzyna

2016-12-01

It has recently been suggested that the adenosine A 2A receptor plays a role in several animal models of depression. Additionally, A 2A antagonists have reversed behavioral deficits and exhibited a profile similar to classical antidepressants. In the present study, imidazo- and pyrimido[2,1-f]purinedione derivatives (KD 66, KD 167, KD 206) with affinity to A 2A receptors but poor A 1 affinity were evaluated for their antidepressant- and anxiolytic-like activity. The activity of these derivatives was tested using a tail suspension and forced swim test, two widely-used behavioral paradigms for the evaluation of antidepressant-like activity. In turn, the anxiolytic activity was evaluated using the four-plate test. The results showed the antidepressant-like activity of pyrimido- and imidazopurinedione derivatives (i.e. KD 66, KD 167 and KD 206) in acute and chronic behavioral tests in mice. KD 66 revealed an anxiolytic-like effect, while KD 167 increased anxiety behaviors. KD 206 had no effect on anxiety. Furthermore, none of the tested compounds increased locomotor activity. Available data support the proposition that the examined compounds with adenosine A 2A receptor affinity may be an interesting target for the development of antidepressant and/or anxiolytic agents. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The Effect of Serotonin-Targeting Antidepressants on Neurogenesis and Neuronal Maturation of the Hippocampus Mediated via 5-HT1A and 5-HT4 Receptors

PubMed Central

Segi-Nishida, Eri

2017-01-01

Antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) specifically increase serotonin (5-HT) levels in the synaptic cleft and are widely used to treat mood and anxiety disorders. There are 14 established subtypes of 5-HT receptors in rodents, each of which has regionally different expression patterns. Many preclinical studies have suggested that the hippocampus, which contains abundant 5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG), is critically involved in the mechanisms of action of antidepressants. This review article will analyze studies demonstrating regulation of hippocampal functions and hippocampus-dependent behaviors by SSRIs and similar serotonergic agents. Multiple studies indicate that 5-HT1A and 5-HT4 receptor signaling in the DG contributes to SSRI-mediated promotion of neurogenesis and increased neurotrophic factors expression. Chronic SSRI treatment causes functions and phenotypes of mature granule cells (GCs) to revert to immature-like phenotypes defined as a “dematured” state in the DG, and to increase monoamine reactivity at the dentate-to-CA3 synapses, via 5-HT4 receptor signaling. Behavioral studies demonstrate that the 5-HT1A receptors on mature GCs are critical for expression of antidepressant effects in the forced swim test and in novelty suppressed feeding; such studies also note that 5-HT4 receptors mediate neurogenesis-dependent antidepressant activity in, for example, novelty-suppressed feeding. Despite their limitations, the collective results of these studies describe a potential new mechanism of action, in which 5-HT1A and 5-HT4 receptor signaling, either independently or cooperatively, modulates the function of the hippocampal DG at multiple levels, any of which could play a critical role in the antidepressant actions of 5-HT-enhancing drugs. PMID:28559799

Risk of manic switch associated with antidepressant therapy in pediatric bipolar depression.

PubMed

Bhowmik, Debajyoti; Aparasu, Rajender R; Rajan, Suja S; Sherer, Jeffrey T; Ochoa-Perez, Melissa; Chen, Hua

2014-12-01

The purpose of this study was to assess the risk of manic switch associated with antidepressants in Medicaid-enrolled pediatric patients with bipolar depression. This retrospective cohort study involved 2003-2007 Medicaid Analytic eXtract (MAX) data from four geographically diverse states. The study sample included children and adolescents (ages 6-18 years) who had received a diagnosis of bipolar disorder on two or more separate occasions or during a hospital discharge, followed by a diagnosis of depression. According to the pharmacotherapy received by these patients in the 30 days around the index bipolar depression diagnosis, patients were categorized into five mutually exclusive groups. Manic switch was defined as having received a diagnosis of mania within 6 weeks after the initiation of bipolar depression treatment. Relative risks of manic switch between antidepressant monotherapy/polytherapy and their alternatives were assessed using Cox proportional hazards model. The robustness of the conventional Cox proportional hazards model toward possible bias caused by unobserved confounders was tested using instrumental variable analysis, and the uncertainty regarding manic switch definition was tested by altering the duration of follow-up. After applying all the selection criteria, 179 antidepressant monotherapy, 1047 second-generation antipsychotic (SGA) monotherapy, 570 mood stabilizer monotherapy, 445 antidepressant polytherapy, and 1906 SGA-mood stabilizer polytherapy users were identified. In Cox proportional hazard analyses, both antidepressant monotherapy and polytherapy exhibited higher risk of manic switch than their alternatives (antidepressant monotherapy vs. SGA monotherapy, hazard ratio [HR]=2.87 [95% CI: 1.10-7.49]; antidepressant monotherapy vs. mood stabilizer monotherapy, HR=1.41 [95% CI: 0.52-3.80); antidepressant polytherapy vs. SGA-mood stabilizer polytherapy, HR=1.61 [95% CI: 0.90-2.89]). However, only the comparison between antidepressant

Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation.

PubMed

Etiévant, A; Oosterhof, C; Bétry, C; Abrial, E; Novo-Perez, M; Rovera, R; Scarna, H; Devader, C; Mazella, J; Wegener, G; Sánchez, C; Dkhissi-Benyahya, O; Gronfier, C; Coizet, V; Beaulieu, J M; Blier, P; Lucas, G; Haddjeri, N

2015-08-01

Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

Pregnancy and postpartum antidepressant use moderates the effects of sleep on depression.

PubMed

Stone, Kristen C; Salisbury, Amy L; Miller-Loncar, Cynthia L; Mattera, Jennifer A; Battle, Cynthia L; Johnsen, Dawn M; O'Grady, Kevin E

2017-10-01

This study examined the course of antidepressant use, sleep quality, and depression severity from pregnancy through 6-month postpartum in women with and without a depressive disorder during pregnancy. Women (N = 215) were interviewed during pregnancy, 1- and 6-month postpartum. Mixed linear models were used to examine the longitudinal course and inter-relationships for the time-varying variables of antidepressant use, subjective sleep quality, and depression severity. Pregnant women with a depressive disorder who did not use antidepressants had more variable depression severity over time with improvements in depression severity by 6-month postpartum. In contrast, the depression severity of their medicated counterparts remained stable and high throughout. Pregnant women without a depressive disorder had worse sleep quality when using antidepressants compared with when they were not. Antidepressant use significantly strengthened the magnitude of the effect of sleep quality on depression severity in women with a depressive disorder during pregnancy. When prenatally depressed women use antidepressants, their sleep disturbance is more highly linked to depression severity than when they do not. Furthermore, antidepressants are not adequately treating the sleep disturbance of these women or their remitted counterparts, leaving both groups vulnerable to significant negative mental and physical health outcomes.

An analysis of the diffusion of new antidepressants: variety, quality, and marketing efforts.

PubMed

Berndt, Ernst R; Bhattacharjya, Ashoke; Mishol, David N; Arcelus, Almudena; Lasky, Thomas

2002-03-01

those for side effects. Marketing efforts respond to science-based events, such as new FDA indication approvals, and to effectiveness and side-effect quality improvements. Total antidepressant sales are positively and significantly related to price reductions, increased marketing efforts, and the level and variety of side effect profiles involving antidepressants. The level and variety of effectiveness does not significantly affect total antidepressant sales. Order of entry effects are important in affecting product market shares, while marketing efforts and relative quality attributes (particularly a more favorable side effect profile) have positive and significant impacts on relative market shares. Since patient response to SSRIs and related products is idiosyncratic, greater product variety facilitates better matching of antidepressant with patient. Much of the growth of the SSRIs and related antidepressants since 1988 can be attributed to increased product attribute variety, to improved changes in side effect quality relative to that of the tricyclics, and to the marketing of those improvements. Marketing efforts play an important role in diffusing product information. Marketing efforts increase considerably following FDA approval for indications other than depression, and also increase with the average effectiveness and the average side effect rating of the products. Whether the relatively minor role that perceived effectiveness has in affecting sales relative to perceived side effect profile is unique to antidepressants, or generalizes to other therapeutic classes, merits further examination.

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. © 2013.

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs.

PubMed

Marek, Gerard J; Day, Mark; Hudzik, Thomas J

2016-03-01

Cognitive dysfunction may be a core feature of major depressive disorder, including affective processing bias, abnormal response to negative feedback, changes in decision making, and increased impulsivity. Accordingly, a translational medicine paradigm predicts clinical action of novel antidepressants by examining drug-induced changes in affective processing bias. With some exceptions, these concepts have not been systematically applied to preclinical models to test new chemical entities. The purpose of this review is to examine whether an empirically derived behavioral screen for antidepressant drugs may screen for compounds, at least in part, by modulating an impulsive biasing of responding and altered decision making. The differential-reinforcement-of-low-rate (DRL) 72-second schedule is an operant schedule with a documented fidelity for discriminating antidepressant drugs from nonantidepressant drugs. However, a theoretical basis for this empirical relationship has been lacking. Therefore, this review will discuss whether response bias toward impulsive behavior may be a critical screening characteristic of DRL behavior requiring long inter-response times to obtain rewards. This review will compare and contrast DRL behavior with the five-choice serial reaction time task, a test specifically designed for assessing motoric impulsivity, with respect to psychopharmacological testing and the neural basis of distributed macrocircuits underlying these tasks. This comparison suggests that the existing empirical basis for the DRL 72-second schedule as a pharmacological screen for antidepressant drugs is complemented by a novel hypothesis that altering impulsive response bias for rodents trained on this operant schedule is a previously unrecognized theoretical cornerstone for this screening paradigm. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

FKBP5/FKBP51 enhances autophagy to synergize with antidepressant action

PubMed Central

Gassen, Nils C; Hartmann, Jakob; Schmidt, Mathias V; Rein, Theo

2015-01-01

Levels of autophagy markers rise upon treatment of cells with antidepressants. However, it was not known whether this phenomenon might be linked to other antidepressant pathways or to any physiological effect. In this punctum, we summarize and discuss our recent findings that provide evidence for a role of the cochaperone FKBP5/FKBP51 (FK506 binding protein 5) in autophagy as a prerequisite for antidepressant action in cells, mice, and humans. FKBP5 associates with BECN1, changes its phosphorylation and protein levels and enhances markers of autophagy and autophagic flux. The effects of antidepressants on autophagy as well as their physiological effects in mice and human depend on FKBP5. PMID:25714272

Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.

PubMed

Cox, Georgina R; Callahan, Patch; Churchill, Rachel; Hunot, Vivien; Merry, Sally N; Parker, Alexandra G; Hetrick, Sarah E

2014-11-30

Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning. To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 June 2014. The register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when

Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine.

PubMed

Fukumoto, Kenichi; Toki, Hidetoh; Iijima, Michihiko; Hashihayata, Takashi; Yamaguchi, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

2017-04-01

The rapid-acting and long-lasting antidepressant effects of ( R,S )-ketamine have recently gained much attention. Although ( S )-ketamine has been studied as an active isomer, recent evidence suggests that ( R )-ketamine exhibits longer-lasting antidepressant effects than ( S )-ketamine in rodents. However, the antidepressant potential of ( R )-ketamine has not been fully addressed. In the present study, we compared the antidepressant effects of ( R )-ketamine with those of ( S )-ketamine in animal models of depression, including a model that is refractory to current medications. Both ( R )-ketamine and ( S )-ketamine exhibited antidepressant effects at 30 minutes as well as at 24 hours after administration in forced-swimming and tail-suspension tests in mice. At 48 hours after administration, however, ( R )-ketamine still exerted a significant antidepressant effect in the tail-suspension test, whereas the effect of ( S )-ketamine was no longer observed. Moreover, ( R )-ketamine, but not ( S )-ketamine, significantly reversed the depressive-like behavior induced by repeated treatments with corticosterone in rats at 24 hours after a single administration. This effect was attenuated by an α -amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, suggesting the involvement of AMPA receptor stimulation in the effects. Both ( R )-ketamine and ( S )-ketamine exhibited practically the same exposure levels in plasma, brain, and cerebrospinal fluid in mice and rats, and both compounds were rapidly eliminated from plasma (<4-8 hours). The present results confirmed the previous findings that ( R )-ketamine exerted longer-lasting antidepressant effects than ( S )-ketamine in animal models of depression. Moreover, our study is the first to demonstrate that ( R )-ketamine exerted a sustained antidepressant effect even in a model that is refractory to currently prescribed antidepressants. Copyright © 2017 by The American Society for Pharmacology and

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

PubMed

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

2015-01-01

Many patients have erroneous views with regard to depression and its management, and it was noted that these attitudes and beliefs significantly affected their adherence rates. The primary aim of this study was to determine the attitudes and beliefs of patients with depression toward depression and antidepressants. A secondary aim was to assess the influence of ethnicity on patients' attitudes and beliefs. The study involved patients with chronic depression being followed up at an outpatient clinic at a government-run hospital in Malaysia. Patients' attitudes and beliefs were assessed using the Antidepressant Compliance Questionnaire. A total of 104 patients of Malay, Chinese, and Indian ethnic groups met the selection criteria. Chinese patients had significantly negative attitudes and beliefs toward depression and antidepressants compared to Malays and Indians (b=-8.96, t 103=-3.22; P<0.05). Component analysis revealed that 59% of patients believed that antidepressants can cause a person to have less control over their thoughts and feelings, while 67% believed that antidepressants could alter one's personality; 60% believed it was okay to take fewer tablets on days when they felt better, while 66% believed that antidepressants helped solve their emotional problems and helped them worry less. Patients had an overall positive view as to the benefits of antidepressants, but the majority had incorrect views as to the acceptable dosing of antidepressants and had concerns about the safety of the medication. Assessing patients' attitudes and beliefs, as well as the impact of their respective cultures, can be used in tailoring psychoeducation sessions accordingly.

Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses

PubMed Central

Gideons, Erinn S.; Kavalali, Ege T.; Monteggia, Lisa M.

2014-01-01

Ketamine is an NMDA receptor (NMDAR) antagonist that elicits rapid antidepressant responses in patients with treatment-resistant depression. However, ketamine can also produce psychotomimetic effects that limit its utility as an antidepressant, raising the question of whether the clinically tolerated NMDAR antagonist memantine possesses antidepressant properties. Despite its similar potency to ketamine as an NMDAR antagonist, clinical data suggest that memantine does not exert rapid antidepressant actions for reasons that are poorly understood. In this study, we recapitulate the ketamine and memantine clinical findings in mice, showing that ketamine, but not memantine, has antidepressant-like effects in behavioral models. Using electrophysiology in cultured hippocampal neurons, we show that ketamine and memantine effectively block NMDAR-mediated miniature excitatory postsynaptic currents in the absence of Mg2+. However, in physiological levels of extracellular Mg2+, we identified key functional differences between ketamine and memantine in their ability to block NMDAR function at rest. This differential effect of ketamine and memantine extends to intracellular signaling coupled to NMDAR at rest, in that memantine does not inhibit the phosphorylation of eukaryotic elongation factor 2 or augment subsequent expression of BDNF, which are critical determinants of ketamine-mediated antidepressant efficacy. These results demonstrate significant differences between the efficacies of ketamine and memantine on NMDAR-mediated neurotransmission that have impacts on downstream intracellular signaling, which we hypothesize is the trigger for rapid antidepressant responses. These data provide a novel framework on the necessary functional requirements of NMDAR-mediated neurotransmission as a critical determinant necessary to elicit rapid antidepressant responses. PMID:24912158

Impact of Medicare Part D on Antidepressant Treatment, Medication Choice and Adherence among Older Adults with Depression

PubMed Central

Donohue, Julie M.; Zhang, Yuting; Men, Aiju; Perera, Subashan; Lave, Judith R.; Hanlon, Joseph T.; Reynolds, Charles F.

2010-01-01

Objectives Depression in older adults is often undertreated due, in part, to medication costs. We examined the impact of improved prescription drug coverage under Medicare Part D on use of antidepressants, medication choice and adherence. Design, Setting and Participants Observational claims-based study of older adults with depression (ICD-9: 296.2, 296.3, 311, 300.4) continuously enrolled in a Medicare managed care plan between 2004–2007. Three groups with limited ($150 or $350 quarterly caps) or no drug coverage in 2004–2005 obtained Part D benefits in 2006. A comparison group had stable employer-sponsored coverage throughout. Measurements Any antidepressant prescription fill, antidepressant choice (tricyclics or monoamine oxidase inhibitors vs. newer antidepressants), and adherence (80% of days covered) in the first 6 months of treatment. Results Part D was associated with increased odds of any antidepressant use among those who previously lacked coverage [Odds Ratio (OR) 1.61, 95% confidence interval (CI) 1.41–1.85] but odds of use did not change among those with limited prior coverage. Use of older antidepressant agents did not change with Part D. All three groups whose coverage improved with Part D had significantly higher odds of 80% of days covered with an antidepressant [OR=1.86 (95% CI, 1.44–2.39) for No coverage, 1.74 (95% CI, 1.25–3.42) for $150 cap; and 1.19 (95% CI 1.06–1.34) for the $350 cap groups]. Conclusions Medicare Part D was associated with improvements in antidepressant use and adherence in depressed older adults who previously had no or limited drug coverage but not with changes in use of older agents. PMID:22123272

Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner.

PubMed

Holubova, Kristina; Kleteckova, Lenka; Skurlova, Martina; Ricny, Jan; Stuchlik, Ales; Vales, Karel

2016-06-01

The aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect. Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests. Blood samples were collected before and after drug administration for analysis of phosphorylated mTOR level. After behavioral testing, brains were removed for evaluation of brain-derived neurotrophic factor (BDNF) in prefrontal cortex (PFC) and hippocampus. Ketamine normalized hyperactivity of OBX animals in EPM and increased the time spent in open arms. Rapamycin pretreatment resulted in elimination of ketamine effect in EPM test. In CM test, ketamine + rapamycin administration led to cognitive impairment not observed in saline-, ketamine-, or saline + rapamycin-treated OBX rats. Prefrontal BDNF content was significantly decreased, and level of mTOR was significantly elevated in OBX groups. OBX animals significantly differed from sham controls in most of the tests used. Treatment had more profound effect on OBX phenotype than controls. Pretreatment with rapamycin eliminated the anxiolytic and antidepressant effects of ketamine in task-dependent manner. The results indicate that ketamine + rapamycin application resulted in impaired stress responses manifested by cognitive deficits in active place avoidance (CM) test. Intensity of stressor (mild vs. severe) used in the behavioral tests had opposite effect on controls and on OBX animals.

[Antidepressants do prevent suicide, at least pending something better...].

PubMed

Courtet, Philippe; Olié, Émilie

2014-01-01

Suicide is a major public health problem worldwide, with about 1.5 million deaths each year France ranks 7th in the EU Patients with depression account for the majority of completed suicides. As most of these individuals are not adequately treated, it is conceivable that better treatment of depression would reduce suicide mortality. However, the last ten years have seen a controversy over a possible suicidogenic effect of antidepressants. Here we summarize data from the different types of studies that have cast a shadow over these drugs which can save lives when used effectively to treat depression. Better knowledge of the pathophysiology of "suicidal behaviour disorder" should identify therapeutic targets for innovative agents capable of preventing suicide.

The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

PubMed Central

Al-Tubuly, RA; Aburawi, SM; Alghzewi, EA; Gorash, ZM; Errwami, S

2008-01-01

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist). Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments.In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors. PMID:21499463

Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid.

PubMed

Peña, E; Mata, M; López-Manzanares, L; Kurtis, M; Eimil, M; Martínez-Castrillo, J C; Navas, I; Posada, I J; Prieto, C; Ruíz-Huete, C; Vela, L; Venegas, B

2016-03-19

Although antidepressants are widely used in Parkinson's disease (PD), few well-designed studies to support their efficacy have been conducted. These clinical guidelines are based on a review of the literature and the results of an AMN movement disorder study group survey. Evidence suggests that nortriptyline, venlafaxine, paroxetine, and citalopram may be useful in treating depression in PD, although studies on paroxetine and citalopram yield conflicting results. In clinical practice, however, selective serotonin reuptake inhibitors are usually considered the treatment of choice. Duloxetine may be an alternative to venlafaxine, although the evidence for this is less, and venlafaxine plus mirtazapine may be useful in drug-resistant cases. Furthermore, citalopram may be indicated for the treatment of anxiety, atomoxetine for hypersomnia, trazodone and mirtazapine for insomnia and psychosis, and bupropion for apathy. In general, antidepressants are well tolerated in PD. However, clinicians should consider the anticholinergic effect of tricyclic antidepressants, the impact of serotonin-norepinephrine reuptake inhibitors on blood pressure, the extrapyramidal effects of antidepressants, and any potential interactions between monoamine oxidase B inhibitors and other antidepressants. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Effect of Antidepressant Medication Use on Emotional Information Processing in Major Depression

PubMed Central

Wells, Tony T.; Clerkin, Elise M.; Ellis, Alissa J.; Beevers, Christopher G.

2013-01-01

Objective Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy participants. This effect is likely relevant to the therapeutic actions of these medications, but has not been studied in patients with Major Depressive Disorder (MDD) taking antidepressants as typically prescribed in the community. Method The authors examined the effects of antidepressant medication on selective attention for emotional stimuli using eye tracking in a sample of 47 participants (21 medicated; 26 non-medicated) with MDD and 47 matched, non-depressed controls. Participants completed a passive viewing eye tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Results: Depressed participants currently taking antidepressant medication and non-depressed healthy control participants demonstrated greater total gaze duration and more fixations for positive stimuli, compared to non-medicated depressed participants. Depressed participants on medication (vs. depressed participants not on medication) also had fewer fixations for dysphoric stimuli. Conclusions Antidepressants, as prescribed in the community to depressed patients, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with prior work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication. PMID:24030200

Effect of antidepressant medication use on emotional information processing in major depression.

PubMed

Wells, Tony T; Clerkin, Elise M; Ellis, Alissa J; Beevers, Christopher G

2014-02-01

Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community. The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication. Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.

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

Ontogeny of SERT Expression and Antidepressant-like Response to Escitalopram in Wild-Type and SERT Mutant Mice.

PubMed

Mitchell, Nathan C; Gould, Georgianna G; Koek, Wouter; Daws, Lynette C

2016-08-01

Depression is a disabling affective disorder for which the majority of patients are not effectively treated. This problem is exacerbated in children and adolescents for whom only two antidepressants are approved, both of which are selective serotonin reuptake inhibitor (SSRIs). Unfortunately SSRIs are often less effective in juveniles than in adults; however, the mechanism(s) underlying age-dependent responses to SSRIs is unknown. To this end, we compared the antidepressant-like response to the SSRI escitalopram using the tail suspension test and saturation binding of [(3)H]citalopram to the serotonin transporter (SERT), the primary target of SSRIs, in juvenile [postnatal day (P)21], adolescent (P28), and adult (P90) wild-type (SERT+/+) mice. In addition, to model individuals carrying low-expressing SERT variants, we studied mice with reduced SERT expression (SERT+/-) or lacking SERT (SERT-/-). Maximal antidepressant-like effects were less in P21 mice relative to P90 mice. This was especially apparent in SERT+/- mice. However, the potency for escitalopram to produce antidepressant-like effects in SERT+/+ and SERT+/- mice was greater in P21 and P28 mice than in adults. SERT expression increased with age in terminal regions and decreased with age in cell body regions. Binding affinity values did not change as a function of age or genotype. As expected, in SERT-/- mice escitalopram produced no behavioral effects, and there was no specific [(3)H]citalopram binding. These data reveal age- and genotype-dependent shifts in the dose-response for escitalopram to produce antidepressant-like effects, which vary with SERT expression, and may contribute to the limited therapeutic response to SSRIs in juveniles and adolescents. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Antidepressant-like effect of food-derived pyroglutamyl peptides in mice.

PubMed

Yamamoto, Yukako; Mizushige, Takafumi; Mori, Yukiha; Shimmura, Yuki; Fukutomi, Ruuta; Kanamoto, Ryuhei; Ohinata, Kousaku

2015-06-01

The N-terminal glutamine residue, exposed by enzymatic cleavage of precursor proteins, is known to be modified to a pyroglutamyl residue with a cyclic structure in not only endogenous but also food-derived peptides. We investigated the effects of wheat-derived pyroglutamyl peptides on emotional behaviors. Pyroglutamyl leucine (pyroGlu-Leu, pEL) and pyroglutamyl glutaminyl leucine (pyroGlu-Gln-Leu, pEQL) exhibited antidepressant-like activity in the tail suspension and forced swim tests in mice. pEQL exhibited more potent antidepressant-like activity than pEL after i.p. and i.c.v. administration. pEQL exhibited antidepressant-like activity at a lower dose than Gln-Gln-Leu, suggesting that pyroglutamyl peptide had more potent activity. To examine whether pyroglutamyl peptides increased hippocampus neurogenesis, associated with the effects of antidepressants, we measured 5-bromo-2'-deoxyuridine (BrdU) incorporation. pEL and pEQL increased BrdU-positive cells in the dentate gyrus of the hippocampus. Intriguingly, pEL did not increase hippocampal mRNA and protein expression of brain-derived neurotrophic factor (BDNF), which is a factor associated with both neuropoietic and antidepressive effects. Thus, pyroglutamyl peptides may enhance hippocampal neurogenesis via a pathway independent of BDNF. We also confirmed that pEL and pEQL were produced in the subtilisin digest of major wheat proteins, glutenin and gliadin, after heat treatment. pEL and pEQL are the first peptides derived from wheat proteins to be shown to exhibit an antidepressant-like activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP-AD 2013 Study.

PubMed

Grover, S; Avasthi, A; Tripathi, A; Tanra, A J; Chee, K Y; He, Y L; Chiu, H Fk; Kuga, H; Lee, M S; Chong, M Y; Udormatn, P; Kanba, S; Yang, S Y; Si, T M; Sim, K; Tan, C H; Shen, W W; Xiang, Y T; Sartorius, N; Shinfuku, N

2015-09-01

To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia. The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort. Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries. Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children.

PubMed

Brown, Hilary K; Ray, Joel G; Wilton, Andrew S; Lunsky, Yona; Gomes, Tara; Vigod, Simone N

2017-04-18

Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded. To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder. Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014. Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery. Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings. There were 35 906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children

Antidepressants May Mitigate the Effects of Prenatal Maternal Anxiety on Infant Auditory Sensory Gating

PubMed Central

Hunter, Sharon K.; Mendoza, Jordan H.; D’Anna, Kimberly; Zerbe, Gary O; McCarthy, LizBeth; Hoffman, Camille; Freedman, Robert; Ross, Randal G.

2013-01-01

Objective Prenatal maternal anxiety has detrimental effects on the resulting offspring’s neurocognitive development, including impaired attentional function. Antidepressants are commonly utilized during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. Using P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, the impact of maternal anxiety and antidepressant use are explored. Method Two hundred forty-two mother-infant dyads were classified relative to maternal history of anxiety and maternal prenatal antidepressant use. Infant P50 auditory sensory gating was recorded during active sleep at a mean± standard deviation of 76 ± 38 days of age. Results In the absence of prenatal antidepressant exposure, infants with mothers with a history of anxiety diagnoses had diminished P50 sensory gating (p<.001). Prenatal antidepressants mitigated the effect of anxiety (uncorrected p=.041). The effect of maternal anxiety was limited to amplitude of response to the second stimulus while antidepressants impacted the amplitude or response to both the first and second stimulus. Conclusion Maternal anxiety disorders are associated less inhibition during infant sensory gating, a performance deficit mitigated by prenatal antidepressant use. This effect may be important in considering the risks and benefits of prenatal antidepressant treatment. Cholinergic mechanisms are hypothesized for both anxiety and antidepressant effects; however the cholinergic receptors involved are likely different for anxiety and antidepressant effects. Additional work focused on understanding how treatment impacts the relationship between maternal prenatal illness and offspring neurocognitive development is indicated. PMID:22581104

In vivo gene expression profiling of the entomopathogenic fungus Beauveria bassiana elucidates its infection stratagems in Anopheles mosquito.

PubMed

Lai, Yiling; Chen, Huan; Wei, Ge; Wang, Guandong; Li, Fang; Wang, Sibao

2017-08-01

The use of entomopathogenic fungi to control mosquitoes is a promising tool for reducing vector-borne disease transmission. To better understand infection stratagems of insect pathogenic fungi, we analyzed the global gene expression profiling of Beauveria bassiana at 36, 60, 84 and 108 h after topical infection of Anopheles stephensi adult mosquitoes using RNA sequencing (RNA-Seq). A total of 5,354 differentially expressed genes (DEGs) are identified over the course of fungal infection. When the fungus grows on the mosquito cuticle, up-regulated DEGs include adhesion-related genes involved in cuticle attachment, Pth11-like GPCRs hypothesized to be involved in host recognition, and extracellular enzymes involved in the degradation and penetration of the mosquito cuticle. Once in the mosquito hemocoel, the fungus evades mosquito immune system probably through up-regulating expression of β-1,3-glucan degrading enzymes and chitin synthesis enzymes for remodeling of cell walls. Moreover, six previous unknown SSCP (small secreted cysteine-rich proteins) are significantly up-regulated, which may serve as "effectors" to suppress host defense responses. B. bassiana also induces large amounts of antioxidant genes to mitigate host-generated exogenous oxidative stress. At late stage of infection, B. bassiana activates a broad spectrum of genes including nutrient degrading enzymes, some transporters and metabolism pathway components, to exploit mosquito tissues and hemolymph as a nutrient source for hyphal growth. These findings establish an important framework of knowledge for further comprehensive elucidation of fungal pathogenesis and molecular mechanism of Beauveria-mosquito interactions.

Reevaluating Antidepressant Selection in Patients With Bruxism and Temporomandibular Joint Disorder.

PubMed

Rajan, Royce; Sun, Ye-Ming

2017-05-01

Temporomandibular joint disorder (TMD) is a broad pain disorder that refers to several conditions affecting the temporomandibular joint of the jaw and the muscles of mastication. As with most pain disorders, a high prevalence of depression and anxiety is associated with TMD. Research has shown that selective serotonin reuptake inhibitors (SSRIs), the first-line drug therapy for major depressive disorder, may not be suitable for TMD patients because SSRIs can induce teeth-grinding, otherwise known as bruxism. This is problematic because bruxism is believed to further exacerbate TMD. Therefore, the purpose of this literature review is to better understand the mechanism of SSRI-induced bruxism, as well as discuss alternative antidepressant options for treating depression and anxiety in patients with bruxism and TMD. Alternative classes of antidepressants reviewed include serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, and monoamine oxidase inhibitors. Findings indicate that dopamine agonists and buspirone are currently the most effective medications to treat the side effects of SSRI-induced bruxism, but results regarding the effectiveness of specific antidepressants that avoid bruxism altogether remain inconclusive.

Antidepressant use in 27 European countries: associations with sociodemographic, cultural and economic factors.

PubMed

Lewer, Dan; O'Reilly, Claire; Mojtabai, Ramin; Evans-Lacko, Sara

2015-09-01

Prescribing of antidepressants varies widely between European countries despite no evidence of difference in the prevalence of affective disorders. To investigate associations between the use of antidepressants, country-level spending on healthcare and country-level attitudes towards mental health problems. We used Eurobarometer 2010, a large general population survey from 27 European countries, to measure antidepressant use and regularity of use. We then analysed the associations with country-level spending on healthcare and country-level attitudes towards mental health problems. Higher country spending on healthcare was strongly associated with regular use of antidepressants. Beliefs that mentally ill people are 'dangerous' were associated with higher use, and beliefs that they 'never recover' or 'have themselves to blame' were associated with lower and less regular use of antidepressants. Contextual factors, such as healthcare spending and public attitudes towards mental illness, may partly explain variations in antidepressant use and regular use of these medications. © The Royal College of Psychiatrists 2015.

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.

Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats

PubMed Central

Choi, Miyeon; Lee, Seung Hoon; Wang, Sung Eun; Ko, Seung Yeon; Song, Mihee; Choi, June-Seek; Duman, Ronald S.; Son, Hyeon

2015-01-01

Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II- and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine. PMID:26647181

Closing the antidepressant efficacy gap between clinical trials and real patient populations.

PubMed

Wade, Alan G

2006-01-01

Overall, patient outcomes in the primary care of depression are seldom as good as those achieved in clinical trials - the "efficacy gap". Many factors contribute to this, including poor patient compliance, poor family and social support and negative media reporting of antidepressants. Indeed, negative media reporting has had far more impact on physicians' prescribing of antidepressants than have regulatory agencies, partly as a result of changing public attitudes. Negative media reports linking SSRIs to increased child suicide rates have also resulted in a decline in the prescribing of SSRIs to this age group, but with no concomitant increase in the prescribing of fluoxetine, the only antidepressant recommended for the treatment of children. There are also inadequacies in the guidelines available to primary care givers that might contribute to the efficacy gap. Guidelines can be too specific for clinical practice - especially where depression coexists with anxiety disorders - and too passive, resulting in delayed or inadequate intervention. Evidence suggests that many physicians prefer to be more proactive. In the recent AHEAD survey, physicians identified faster resolution of symptoms as the property most desirable for improving antidepressant therapy. There is recent evidence that structured long-term therapy and easily-implemented measurement-based care procedures can improve remission rates and help bridge the efficacy gap. If these can be allied with greater public/media understanding of depression and its treatment, along with improved guidelines, then significant progress can be anticipated in the management of mood disorders.

Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants.

PubMed

Weissman, Alicia M; Levy, Barcey T; Hartz, Arthur J; Bentler, Suzanne; Donohue, Micca; Ellingrod, Vicki L; Wisner, Katherine L

2004-06-01

The available data on antidepressant levels in nursing infants were analyzed in order to calculate average infant drug levels and determine what factors influence plasma drug levels in breast-feeding infants of mothers treated with antidepressants. Electronic searches of MEDLINE, PreMEDLINE, Current Contents, Biological Abstracts, and PsycINFO from 1966 through July 2002 followed by bibliographic searches identified 67 relevant studies (two unpublished). By consensus the authors identified 57 studies of maternal plasma, breast milk, and/or infant plasma antidepressant levels from nursing mother-infant pairs, measured by liquid chromatography. Infants with recent prenatal exposure and symptomatic infants included in case reports were analyzed separately. Infant plasma levels were standardized against the average maternal level for each drug. The average infant-maternal plasma ratio was calculated for each drug, and correlations of infant plasma level to maternal dose, maternal plasma level, and breast milk level were calculated. Nortriptyline, paroxetine, and sertraline usually produce undetectable infant levels. Of drugs currently used, fluoxetine produces the highest proportion (22%) of infant levels that are elevated above 10% of the average maternal level. Based on smaller numbers, the data on citalopram indicate that it produces elevated levels in 17% of infants. The milk-to-plasma ratios for 11 antidepressants had a statistically significant negative association with the percentage of the drug bound to protein. Nortriptyline, paroxetine, and sertraline may be preferred choices in breast-feeding women. Minimizing the maternal dose may be helpful with citalopram. Current data do not support monitoring breast milk levels in individual patients. Future researchers should report maternal, breast milk, and infant antidepressant levels along with other appropriate variables.

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

PubMed Central

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

2015-01-01

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

Comparative risk of self-harm hospitalization amongst depressive disorder patients using different antidepressants: a population-based cohort study in Taiwan.

PubMed

Wu, C-S; Liao, S-C; Tsai, Y-T; Chang, S-S; Tsai, H-J

2017-01-01

The aim of the study was to evaluate the comparative risk of self-harm associated with the use of different antidepressants. A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950-E958 and E980-E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment. There were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person-years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5-7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40-6.45], milnacipran (aHR = 2.34, 95% CI 1.24-4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06-1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30-0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline). The risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors.

Optogenetic stimulation of infralimbic PFC reproduces ketamine's rapid and sustained antidepressant actions.

PubMed

Fuchikami, Manabu; Thomas, Alexandra; Liu, Rongjian; Wohleb, Eric S; Land, Benjamin B; DiLeone, Ralph J; Aghajanian, George K; Duman, Ronald S

2015-06-30

Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.

[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.

S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms

PubMed Central

Mendez-David, Indira; Guilloux, Jean-Philippe; Papp, Mariusz; Tritschler, Laurent; Mocaer, Elisabeth; Gardier, Alain M.; Bretin, Sylvie; David, Denis J.

2017-01-01

Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor’s (AMPAR) activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM) possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S 47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT) and in the Chronic Mild Stress (CMS) model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively) were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM), open field (OF), splash test (ST), forced swim test (FST), tail suspension test (TST), fur coat state and novelty suppressed feeding (NSF) as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.). In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p.) during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model), neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state’s deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg) seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg) and EPM (from 1 mg/kg). In the CMS rat

Reviewing long-term antidepressants can reduce drug burden: a prospective observational cohort study

PubMed Central

Johnson, Chris F; Macdonald, Hector J; Atkinson, Pauline; Buchanan, Alasdair I; Downes, Noreen; Dougall, Nadine

2012-01-01

Background Antidepressant prescribing continues to rise. Contributing factors are increased long-term prescribing and possibly the use of higher selective serotonin re-uptake inhibitor (SSRI) doses. Aim To review general practice patients prescribed the same antidepressant long-term (≥2 years) and evaluate prescribing and management pre and post-review. Design and setting Prospective observational cohort study using routine data from 78 urban general practices, Scotland. Method All patients prescribed antidepressants (excluding amitriptyline) for ≥2 years were identified from records November 2009 to March 2010. GPs selected patients for face-to-face review of clinical condition and medication, December 2009 to September 2010. Pre- and post-review data were collected; average antidepressant doses and changes in prescribed daily doses were calculated. Onward referral to support services was recorded. Results 8.6% (33 312/388 656) of all registered patients were prescribed an antidepressant, 47.1% (15 689) were defined as long-term users and 2849 (18.2%) were reviewed. 811 (28.5%) patients reviewed had a change in antidepressant therapy: 7.0% stopped, 12.8% reduced dose, 5.3% increased dose, and 3.4% changed antidepressant, resulting in 9.5% (95% CI = 9.1% to 9.8% P<0.001) reduction in prescribed daily dose and 8.1% reduction in prescribing costs. 6.3% were referred onwards, half to NHS Mental Health Services. Pre-review SSRI doses were 10–30% higher than previously reported. Conclusion Almost half of all people prescribed antidepressants were long-term users. Appropriate reductions in prescribing can be achieved by reviewing patients. Higher SSRI doses may be contributing to current antidepressant growth. PMID:23211181

Managing inadequate antidepressant response in depressive illness.

PubMed

Haddad, Peter M; Talbot, Peter S; Anderson, Ian M; McAllister-Williams, R Hamish

2015-09-01

Depression frequently fails to respond to initial treatment. Predominantly meta-analyses and RCTs but supplemented where necessary by additional data and the authors' clinical experience. A systematic assessment to identify remedial causes of poor response should be followed by planned sequential treatment trials. Joint decision making by the patient and clinician is essential. Strategies with the strongest support are antidepressant augmentation with lithium or second generation antipsychotics and adding cognitive behavioural treatment. Electroconvulsive therapy is highly effective in resistant depression but there is a high relapse rate when treatment ends. Some pharmacological strategies have inconsistent data (e.g. antidepressant combinations, T3 augmentation) or limited preliminary data (e.g. ketamine, antidepressant augmentation with pramipexole). The efficacy of vagus nerve stimulation, deep brain stimulation and repetitive transcranial magnetic stimulation is unclear. A greater understanding of the causes of depression may assist the development of more effective treatments. Role of glutamate antagonists and psychological treatments, other than cognitive behavioural therapy, as adjunctive treatments. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Neurotensin NTS1 Receptor Agonist PD149163 Produces Antidepressant-Like Effects in the Forced Swim Test: Further Support for Neurotensin as a Novel Pharmacologic Strategy for Antidepressant Drugs.

PubMed

Carey, Lawrence M; Rice, Remington J; Prus, Adam J

2017-08-01

Preclinical Research Neurotensin is a nonbrain penetrant neuropeptide neurotransmitter that alters dopaminergic and serotonergic neurotransmission. Previous animal behavioral studies have demonstrated that intra-ventral tegmental administration of neurotensin and system administration of the selective neurotensin NTS 1 receptor agonist, PD149163 produce antidepressant-like effects in a forced swim test and a differential reinforcement of low rate task, respectively. The present study sought to expand upon these past findings by assessing systemic administration of PD149163 in a forced swim test, a primary antidepressant preclinical screening model, in mice. The tricyclic antidepressant drug imipramine was tested for comparison, and both compounds were also assessed in an open field test. Both PD149163 and imipramine reduced time spent immobile, an antidepressant-like effect, in the forced swim test. The highest dose of each compound significantly reduced locomotor activity. These findings provide further evidence for the putative antidepressant effects for PD149163 and suggest that NTS 1 receptor activation may be a novel pharmacologic strategy for antidepressant drug development. Drug Dev Res 78 : 196-202, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Do continued antidepressants protect against dementia in patients with severe depressive disorder?

PubMed

Kessing, Lars Vedel; Forman, Julie Lyng; Andersen, Per Kragh

2011-11-01

Studies on humans show that depressive disorder is associated with an increased risk of developing cognitive dysfunction, and animal studies suggest that antidepressants may have neuroprotective abilities. On the basis of these observations, it was hypothesized that treatment with antidepressants may decrease the risk of developing dementia in patients with depression. We investigated whether continued treatment with antidepressants is associated with a decreased rate of dementia in a population of patients discharged from psychiatric healthcare service with a diagnosis of depression. We used register data on all prescribed antidepressants in all patients discharged from psychiatric healthcare service with a diagnosis of depression and with subsequent diagnoses of dementia in Denmark from 1995 to 2005. A total of 37 658 patients with a diagnosis of depression at their first psychiatric contact and who were exposed to antidepressants after discharge were included in the study. A total of 2007 patients (5.3%) were subsequently diagnosed with dementia of any kind. The rate of dementia decreased during periods of two or more prescriptions of older antidepressants compared with the period of only one prescription of older antidepressants [relative risk (RR)=0.83 (95% confidence interval (CI)=0.70-0.98)]. This finding was replicated with Alzheimer's disease as the outcome [RR=0.66 (95% CI=0.47-0.94)] but not with dementia of other kinds as the outcome [RR=0.88 (95% CI=0.73-1.06)]. In contrast, during periods of continued use of selective serotonin reuptake inhibitors or newer nonselective serotonin reuptake inhibitors, the rate of dementia was not decreased, regardless of the subtype of dementia. It was concluded that continued long-term treatment with older antidepressants is associated with a reduced rate of dementia in patients treated in psychiatric healthcare settings, whereas continued treatment with other kinds of antidepressants is not. Methodological reasons for

Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice.

PubMed

Lin, Jen-Cheng; Lee, Mei-Yi; Chan, Ming-Huan; Chen, Yi-Chyan; Chen, Hwei-Hsien

2016-09-01

Ketamine is emerging as a new hope against depression, but ketamine-associated psychotomimetic effects limit its clinical use. An adjunct therapy along with ketamine to alleviate its adverse effects and even potentiate the antidepressant effects might be an alternative strategy. Betaine, a methyl derivative of glycine and a dietary supplement, has been shown to have antidepressant-like effects and to act like a partial agonist at the glycine site of N-methyl-D-aspartate receptors (NMDARs). Accordingly, betaine might have potential to be an adjunct to ketamine treatment for depression. The antidepressant-like effects of ketamine and betaine were evaluated by forced swimming test and novelty suppressed feeding test in mice. Both betaine and ketamine produced antidepressant-like effects. Furthermore, we determined the effects of betaine on ketamine-induced antidepressant-like and psychotomimetic behaviors, motor incoordination, hyperlocomotor activity, and anesthesia. The antidepressant-like responses to betaine combined with ketamine were stronger than their individual effects. In contrast, ketamine-induced impairments in prepulse inhibition, novel object recognition test, social interaction, and rotarod test were remarkably attenuated, whereas ketamine-induced hyperlocomotion and loss of righting reflex were not affected by betaine. These findings revealed that betaine could enhance the antidepressant-like effects, yet block the psychotomimetic effects of ketamine, suggesting that betaine can be considered as an add-on therapy to ketamine for treatment-resistant depression and suitable for the treatment of depressive symptoms in patients with schizophrenia.

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

PubMed Central

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

2010-01-01

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

Antidepressant medications and osteoporosis.

PubMed

Rizzoli, R; Cooper, C; Reginster, J-Y; Abrahamsen, B; Adachi, J D; Brandi, M L; Bruyère, O; Compston, J; Ducy, P; Ferrari, S; Harvey, N C; Kanis, J A; Karsenty, G; Laslop, A; Rabenda, V; Vestergaard, P

2012-09-01

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures. Copyright © 2012 Elsevier Inc. All rights reserved.

Association between depressive symptoms and metabolic syndrome is not explained by antidepressant medication: results from the PPP-Botnia Study.

PubMed

Pyykkönen, Antti-Jussi; Räikkönen, Katri; Tuomi, Tiinamaija; Eriksson, Johan G; Groop, Leif; Isomaa, Bo

2012-05-01

To study whether the frequently reported association between depressive symptoms and the metabolic syndrome (MetS) and its individual components are secondary to the use of antidepressant medication and to established diabetes or cardiovascular diseases (CVD). A population-based, random sample of 4,967 women and men aged 18-75 years. MetS was defined according to the new, harmonized criteria. Glucose tolerance was assessed by oral glucose tolerance test (OGTT). CVD, depressive symptoms, and use of antidepressant medication were self-reported. The odds for having the MetS increased over 10%for each standard deviation increase in depressive symptoms. Users of antidepressant medication had more than 50% increased odds for having the MetS. Depressive symptoms were also associated with higher glucose response during the OGTT, higher serum triglyceride and lower HDL-cholesterol concentrations, and higher waist circumference, while use of antidepressant medication was associated with higher triglycerides, waist circumference, and systolic blood pressure. The associations of depressive symptoms were not secondary to use of antidepressant medication and were not explained by established diabetes or CVD. Depressive symptoms, the MetS, and the individual components of MetS are related. These associations are not driven by use of antidepressant medication, established diabetes, or CVD.

Trajectories of change in depression severity during treatment with antidepressants.

PubMed

Uher, R; Muthén, B; Souery, D; Mors, O; Jaracz, J; Placentino, A; Petrovic, A; Zobel, A; Henigsberg, N; Rietschel, M; Aitchison, K J; Farmer, A; McGuffin, P

2010-08-01

Response and remission defined by cut-off values on the last observed depression severity score are commonly used as outcome criteria in clinical trials, but ignore the time course of symptomatic change and may lead to inefficient analyses. We explore alternative categorization of outcome by naturally occurring trajectories of symptom change. Growth mixture models were applied to repeated measurements of depression severity in 807 participants with major depression treated for 12 weeks with escitalopram or nortriptyline in the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent trajectory classes were validated as outcomes in drug efficacy comparison and pharmacogenetic analyses. The final two-piece growth mixture model categorized participants into a majority (75%) following a gradual improvement trajectory and the remainder following a trajectory with rapid initial improvement. The rapid improvement trajectory was over-represented among nortriptyline-treated participants and showed an antidepressant-specific pattern of pharmacogenetic associations. In contrast, conventional response and remission favoured escitalopram and produced chance results in pharmacogenetic analyses. Controlling for drop-out reduced drug differences on response and remission but did not affect latent trajectory results. Latent trajectory mixture models capture heterogeneity in the development of clinical response after the initiation of antidepressants and provide an outcome that is distinct from traditional endpoint measures. It differentiates between antidepressants with different modes of action and is robust against bias due to differential discontinuation.

Beyond Ketamine: New Approaches to the Development of Safer Antidepressants.

PubMed

Chaki, Shigeyuki

2017-01-01

Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention. The first approach includes stereoisomers of ketamine, (R)-ketamine and (S)-ketamine. Although (S)-ketamine has been considered as the active stereoisomer of racemic ketamine, recently, (R)-ketamine has been demonstrated to exert even more prolonged antidepressant effects in animal models than (S)-ketamine. Moreover, ketamine is rapidly metabolized into several metabolites, and some metabolites are speculated as being active substances exerting antidepressant effects. Of such metabolites, one in particular, namely, (2R,6R)-hydroxynorketamine, has been reported to be responsible for the antidepressant effects of ketamine. The second approach includes agents acting on the NMDA receptor, such as glycine site modulators and GluN2B subunit-selective antagonists. These agents have been tested in patients with treatment-resistant depression, and have been found to exhibit rapid antidepressant effects like ketamine. The above approaches may be useful to overcome the drawbacks of ketamine. Elucidation of the mechanisms of action of ketamine may pave the way for the development of antidepressant that are safer, but as potent and rapidly acting as ketamine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Beyond Ketamine: New Approaches to the Development of Safer Antidepressants

PubMed Central

Chaki, Shigeyuki

2017-01-01

Background: Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Methods: Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention. Results: The first approach includes stereoisomers of ketamine, (R)-ketamine and (S)-ketamine. Although (S)-ketamine has been considered as the active stereoisomer of racemic ketamine, recently, (R)-ketamine has been demonstrated to exert even more prolonged antidepressant effects in animal models than (S)-ketamine. Moreover, ketamine is rapidly metabolized into several metabolites, and some metabolites are speculated as being active substances exerting antidepressant effects. Of such metabolites, one in particular, namely, (2R,6R)-hydroxynorketamine, has been reported to be responsible for the antidepressant effects of ketamine. The second approach includes agents acting on the NMDA receptor, such as glycine site modulators and GluN2B subunit-selective antagonists. These agents have been tested in patients with treatment-resistant depression, and have been found to exhibit rapid antidepressant effects like ketamine. Conclusion: The above approaches may be useful to overcome the drawbacks of ketamine. Elucidation of the mechanisms of action of ketamine may pave the way for the development of antidepressant that are safer, but as potent and rapidly acting as ketamine. PMID:28228087

Antidepressant-like activity of plumbagin in unstressed and stressed mice.

PubMed

Dhingra, Dinesh; Bansal, Sudha

2015-10-01

Plumbagin has been reported to be neuroprotective, so it might possess antidepressant activity. Therefore, the present study was designed to explore the antidepressant potential of plumbagin in unstressed and stressed mice. Depression-like behavior was induced in Swiss male albino mice by subjecting them to unpredictable mild stress daily for 21 successive days. Plumbagin (4, 8 and 16mg/kg, po) and imipramine (15mg/kg, po) were administered for 3 successive weeks to separate groups of unstressed and stressed mice. Tail suspension test and sucrose preference test were used to evaluate antidepressant effect of the drugs. Highest dose (16mg/kg) of plumbagin and imipramine significantly decreased immobility period of unstressed and stressed mice in tail suspension test as compared to their respective controls. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. The drugs did not significantly affect locomotor activity of mice. Antidepressant-like activity of plumbagin was found to be comparable to imipramine. Plumbagin and imipramine significantly inhibited brain MAO-A activity, decreased plasma nitrite, brain malondialdehyde and catalase levels; and increased reduced glutathione levels of unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Antidepressant-like activity of plumbagin in unstressed and stressed mice might be through inhibition of brain MAO-A activity and improvement of antioxidant status. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of plumbagin in stressed mice. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Synthesis and structure-activity relationship of novel cinnamamide derivatives as antidepressant agents.

PubMed

Han, Min; Ma, Xiaohui; Jin, Yuanpeng; Zhou, Wangyi; Cao, Jing; Wang, Yahu; Zhou, Shuiping; Wang, Guocheng; Zhu, Yonghong

2014-11-15

Cinnamamide 3a, a leading compound with antidepressant-like activity, and its derivatives were synthesized and their antidepressant activity and structure-activity relationship were investigated. Most of the compounds with trifluoromethyl group in methylenedioxyphenyl moiety (3f, 4b-c and 6a-b) exhibited significant antidepressant activity, measured in terms of percentage decrease in immobility duration by tail suspension test. In addition, the dose-dependent antidepressant effect of the most potent compound 3f was subsequently confirmed in tail suspension test and forced swim test. The test results showed that 3f was equal to or more effective than the standard drug fluoxetine at a concentration of 10mg/kg. Furthermore, compound 3f did not show any central nervous system stimulant properties in the open-field test and the preliminary results were promising enough to warrant further detailed antidepressant research around this scaffold. Copyright © 2014 Elsevier Ltd. All rights reserved.

Management of sexual side effects of antidepressant therapy.

PubMed

Hirschfeld, R M

1999-01-01

Sexual dysfunction occurs in over one third of the general population and has many causes, including psychosocial factors, general medical illness, nonpsychiatric medication, psychiatric disorders, and psychotropic medications. Psychosocial causes are the most prevalent, but many frequently used medications, such as diuretics, beta-blockers, and H2-blockers, can also cause sexual dysfunction. Sexual dysfunctions occur in many psychiatric disorders, including mood disorders, schizophrenia, substance abuse, and anxiety disorders. In addition, over half the patients with major depression will have some sexual dysfunction. Although much attention has been paid to sexual dysfunction associated with the selective serotonin reuptake inhibitors (SSRIs), many other commonly used psychotropics are associated with a variety of sexual dysfunction, including haloperidol, benzodiazepines, stimulants, and drugs of abuse. With regard to SSRIs, sexual dysfunction occurs in 50% or more of such patients, which is substantially higher than the rates reported in the Physicians' Desk Reference. The reason for this discrepancy is that patients will not spontaneously report sexual problems and must be questioned about such problems directly. A variety of strategies exist to manage antidepressant-induced sexual dysfunction, including waiting, reducing the antidepressant dose, use of drug holidays, use of adjunctive pharmacotherapy, and switching antidepressants. Use of an antidepressant with a low prevalence of sexual side effects, such as bupropion, nefazodone, and mirtazapine, may also be considered.

Antidepressants detection and quantification in whole blood samples by GC-MS/MS, for forensic purposes.

PubMed

Truta, Liliana; Castro, André L; Tarelho, Sónia; Costa, Pedro; Sales, M Goreti F; Teixeira, Helena M

2016-09-05

Depression is among the most prevalent psychiatric disorders of our society, leading to an increase in antidepressant drug consumption that needs to be accurately determined in whole blood samples in Forensic Toxicology Laboratories. For this purpose, this work presents a new gas chromatography tandem mass spectrometry (GC-MS/MS) method targeting the simultaneous and rapid determination of 14 common Antidepressants in whole blood: 13 Antidepressants (amitriptyline, citalopram, clomipramine, dothiepin, fluoxetine, imipramine, mianserin, mirtazapine, nortryptiline, paroxetine, sertraline, trimipramine and venlafaxine) and 1 Metabolite (N-desmethylclomipramine). Solid-phase extraction was used prior to chromatographic separation. Chromatographic and MS/MS parameters were selected to improve sensitivity, peak resolution and unequivocal identification of the eluted analyte. The detection was performed on a triple quadrupole tandem MS in selected ion monitoring (SIM) mode in tandem, using electronic impact ionization. Clomipramine-D3 and trimipramine-D3 were used as deutered internal standards. The validation parameters included linearity, limits of detection, lower limit of quantification, selectivity/specificity, extraction efficiency, carry-over, precision and robustness, and followed internationally accepted guidelines. Limits of quantification and detection were lower than therapeutic and sub-therapeutic concentration ranges. Overall, the method offered good selectivity, robustness and quick response (<16min) for typical concentration ranges, both for therapeutic and lethal levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Adapted Finnegan scoring list for observation of anti-depressant exposed infants.

PubMed

Kieviet, Noera; van Ravenhorst, Mariëtte; Dolman, Koert M; van de Ven, Peter M; Heres, Marion; Wennink, Hanneke; Honig, Adriaan

2015-01-01

The Finnegan scoring list (FSL) is widely used to screen for poor neonatal adaptation in infants exposed to anti-depressants in utero. However, the large number of FSL-items and differential weighing of each item is time consuming. The aim of this study was to shorten and simplify the FSL yet preserving its clinimetric properties. This observational study examined infants exposed to an anti-depressant during pregnancy admitted for at least 72 h on a maternity ward. Trained nurses completed the FSL three times daily. Items for the adapted FSL were selected through forward analysis whereby the number of selected items was based on the area under the curve (AUC). Internal validity was assessed by cross-validation. 183 infants met the inclusion criteria. By forward analysis eight equally-weighed items resulted in an AUC of 0.91. In cross-validation, the mean AUC was 0.89 for 8 items. This adapted FSL had a sensitivity of 97.7% and specificity of 37.0% and a sensitivity of 41.9% and specificity of 86.2% regarding a cut-off of, respectively, 1 and 2. An adapted FSL with eight equally-weighed items has acceptable clinimetric properties and can serve as an easy to apply screening tool in infants exposed to anti-depressants during pregnancy.

Antidepressant adherence patterns in older patients: use of a clustering method on a prescription database.

PubMed

Braunstein, David; Hardy, Amélie; Boucherie, Quentin; Frauger, Elisabeth; Blin, Olivier; Gentile, Gaétan; Micallef, Joëlle

2017-04-01

According to the World Health Organization, depression will become the second most important cause of disability worldwide by 2020. Our objective was to identify patterns of adherence to antidepressant treatments in older patients using several indicators of adherence and to characterize these patterns in terms of medication exposure. We conducted a retrospective cohort study using the French National Health Insurance reimbursement database. Incident antidepressant users aged more than 65 were included from July 1, 2010, to June 30, 2011, and followed up for 18 months. Antidepressant and other psychotropic drugs (opioids, benzodiazepines, antipsychotics, anti-epileptics) were recorded. Adherence to antidepressant treatment was assessed by several measures including proportion of days covered, discontinuation periods, persistence of treatment, and doses dispensed. Patients were classified according to their adherence patterns using a mixed clustering method. We identified five groups according to antidepressant adherence. One group (n = 7505, 26.9%) was fully adherent with regard to guidelines on antidepressant use. Two patterns of nonadherent users were identified: irregular but persistent users (n = 5131, 18.4%) and regular but nonpersistent users (n = 9037, 32.4%). Serotonin reuptake inhibitors were the most frequently dispensed antidepressant class (70.6%), followed by other antidepressants (43.3%, mainly serotonin-norepinephrine reuptake inhibitors and tianeptine) and tricyclic antidepressants (TCAs) (13.4%). Nonadherent users more frequently had a dispensing of TCA, opioid, and anti-epileptic medication than adherent users. Health policies to improve adherence to antidepressant treatment may require better training of physicians and pharmacists, insisting on the important role of the continuation period of antidepressant treatment. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Decisional conflict among women considering antidepressant medication use in pregnancy.

PubMed

Walton, Georgia D; Ross, Lori E; Stewart, Donna E; Grigoriadis, Sophie; Dennis, Cindy-Lee; Vigod, Simone

2014-12-01

The purpose of this study was to examine decision-making among women considering antidepressant medication use in pregnancy. Decisional conflict was assessed using the Decisional Conflict Scale (DCS) among pregnant women considering antidepressant medication treatment (N = 40). Overall DCS and subscale scores were compared between women who were antidepressant users and non-users. Semi-structured interviews (N = 10) explored barriers and facilitators of decision-making. Twenty-one women (52 %) had moderate or high decisional conflict (DCS ≥ 25). Overall DCS scores did not differ between groups, but antidepressant use was associated with feeling more adequately informed (subscale mean 17.5, SD 17.9 vs. 42.1, SD 23.8, p = 0.001) and clear about values (subscale mean 16.7, SD 15.1 vs. 29.8, SD 24.0, p = 0.043). Barriers to decision-making were (1) difficulty weighing maternal versus infant health, (2) lack of high quality information, (3) negative external influences, and (4) emotional reactions to decision-making. Facilitators were (1) interpersonal supports, (2) accessible subspecialty care, and (3) severe depressive symptoms. Many pregnant women facing decisions regarding antidepressant medication use experience decisional conflict. Interventions that provide accurate information, assistance with weighing risks and benefits of treatment, management of problematic external influences, and emotional support may reduce decisional conflict and facilitate the decision-making process.

Antidepressant Efficacy for Depression in Children and Adolescents: Industry- and NIMH-Funded Studies.

PubMed

Walkup, John T

2017-05-01

Significant controversy surrounds the efficacy of the newer antidepressants for children and adolescents with depression. The controversy largely hinges on meta-analyses of studies that suggest that antidepressants are minimally effective, not effective, or equivalent to placebo. In this review, the author discusses several scientific and clinical complexities that are important to understand in reviewing the antidepressant literature: the strengths and weaknesses of meta-analyses; the scientific and regulatory context for the large number of antidepressant trials in the late 1990s and early 2000s; and the distinction between a negative trial, where the treatment does not demonstrate efficacy, and a failed trial, where methodological problems make it impossible to draw any conclusion about efficacy. It is the premise of this review that meta-analyses that include the large number of industry-sponsored antidepressant trials distort the picture of antidepressant efficacy for teen depression. Industry-sponsored child and adolescent depression trials suffer from a number of implementation challenges and should be considered failed trials that are largely uninformative and not eligible to be included in efficacy meta-analyses. In contrast to the industry-sponsored trials, depression trials funded by the National Institute of Mental Health (NIMH) (N=2) are characterized by many methodological strengths, lower placebo response rates (30%-35%), and meaningful between-group differences (25%-30%) that support antidepressant efficacy. The NIMH-funded trials, taken together with the demonstrated efficacy of the serotonin reuptake inhibitors for childhood-onset obsessive-compulsive disorder and the anxiety disorders, suggest a broad and important role for antidepressant medications in pediatric internalizing conditions.

Vascular Endothelial Growth Factor-dependent Spinogenesis Underlies Antidepressant-like Effects of Enriched Environment*

PubMed Central

Huang, Yu-Fei; Yang, Chih-Hao; Huang, Chiung-Chun; Hsu, Kuei-Sen

2012-01-01

Current antidepressant treatments remain limited by poor efficacy and a slow onset of action. Increasing evidence demonstrates that enriched environment (EE) treatment can promote structural and behavioral plasticity in the brain and dampen stress-induced alterations of neuroplasticity. Here, we have examined whether short term exposure to EE is able to produce antidepressant-like effects. Our results show that housing adult mice in an EE cage for 7 days led to antidepressant-like behavioral profiles and a significant increase in the number of dendritic spines in hippocampal CA1 pyramidal neurons. These EE-induced antidepressant-like effects are primarily attributed to increased vascular endothelial growth factor (VEGF) expression through a hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional mechanism. Blockade of HIF-1α synthesis by lentiviral infection with HIF-1α small hairpin RNAs completely blocked the increase in expression of VEGF and the antidepressant-like effects induced by EE. Moreover, no significant antidepressant-like effects were observed with EE treatment in VEGF receptor 2 (Flk-1) knock-out mice. The increase in HIF-1α expression in the hippocampus induced by EE was associated with a decrease in endogenous levels of microRNA-107 (miR-107). Overexpression of miR-107 in the hippocampus completely blocked EE-induced HIF-1α expression and the antidepressant-like effects. These results support a model in which the down-regulation of miR-107, acting through HIF-1α, mediates VEGF-dependent spinogenesis to underlie the EE-induced antidepressant-like effects. PMID:23074224

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

PubMed Central

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

2012-01-01

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

Antidepressant Flavonoids and Their Relationship with Oxidative Stress

PubMed Central

Hritcu, Lucian; Ionita, Radu; Postu, Paula Alexandra; Gupta, Girish Kumar; Turkez, Hasan; Lima, Tamires Cardoso; Carvalho, Caroline Uchôa Souza

2017-01-01

Depression is a serious disorder that affects hundreds of millions of people around the world and causes poor quality of life, problem behaviors, and limitations in activities of daily living. Therefore, the search for new therapeutic options is of high interest and growth. Research on the relationship between depression and oxidative stress has shown important biochemical aspects in the development of this disease. Flavonoids are a class of natural products that exhibit several pharmacological properties, including antidepressant-like activity, and affects various physiological and biochemical functions in the body. Studies show the clinical potential of antioxidant flavonoids in treating depressive disorders and strongly suggest that these natural products are interesting prototype compounds in the study of new antidepressant drugs. So, this review will summarize the chemical and pharmacological perspectives related to the discovery of flavonoids with antidepressant activity. The mechanisms of action of these compounds are also discussed, including their actions on oxidative stress relating to depression. PMID:29410733

Effects of antidepressant drugs on histamine-H/sub 1/ receptors in the brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hall, H.; Oegren, S.O.

1984-02-06

The histamine-H/sub 1/ receptor blocking properties of a number of structurally different antidepressant drugs have been evaluated using a /sup 3/H-mepyramine binding assay and a guinea-pig ileum preparation. The tricyclic antidepressants all inhibited the histamine-H/sub 1/ receptor. Some newer antidepressant drugs, such as zimeldine and nomifensine were devoid of activity while others, such as iprindole and mianserin were very potent. It is concluded that antagonistic effects on the histamine-H/sub 1/ receptor is not associated with the therapeutic efficacy in depression, but may contribute to the sedative effects of the antidepressant drugs.

Comparative Safety of Antidepressant Agents for Children and Adolescents Regarding Suicidal Acts

PubMed Central

Schneeweiss, Sebastian; Patrick, Amanda R.; Solomon, Daniel H.; Dormuth, Colin R.; Miller, Matt; Mehta, Jyotsna; Lee, Jennifer C.; Wang, Philip S.

2010-01-01

OBJECTIVE The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents. METHODS We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death. RESULTS Of 20 906 children who initiated antidepressant therapy, 16 774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9–30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54–1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46–2.43]), paroxetine (RR: 0.80 [95% CI: 0.47–1.37]), and sertraline (RR: 1.02 [95% CI: 0.56–1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43–2.00]). CONCLUSION Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants. PMID:20385637

A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study.

PubMed

Sharma, Anup; Barrett, Marna S; Cucchiara, Andrew J; Gooneratne, Nalaka S; Thase, Michael E

2017-01-01

To evaluate feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. Patients with MDD (defined by DSM-IV-TR) who were depressed despite ≥ 8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015. In the ITT sample (n = 25), the SKY arm (n = 13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n = 12) (-9.77 vs 0.50, P = .0032). SKY also showed greater reduction in BDI total score versus waitlist control (-17.23 vs -1.75, P = .0101). Mean changes in BAI total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: -5.19; 95% CI, -0.93 to -9.34; P = .0097; completer mean difference: -6.23; 95% CI, -1.39 to -11.07; P = .0005). No adverse events were reported. Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants. ClinicalTrials.gov identifier: NCT02616549. © Copyright 2016 Physicians Postgraduate Press, Inc.

Magnetic solid phase extraction coupled with desorption corona beam ionization-mass spectrometry for rapid analysis of antidepressants in human body fluids.

PubMed

Chen, Di; Zheng, Hao-Bo; Huang, Yun-Qing; Hu, Yu-Ning; Yu, Qiong-Wei; Yuan, Bi-Feng; Feng, Yu-Qi

2015-08-21

Ambient ionization techniques show good potential in rapid analysis of target compounds. However, a direct application of these ambient ionization techniques for the determination of analytes in a complex matrix is difficult due to the matrix interference and ion suppression. To resolve this problem, here we developed a strategy by coupling magnetic solid phase extraction (MSPE) with desorption corona beam ionization (DCBI)-mass spectrometry (MS). As a proof of concept, the pyrrole-coated Fe3O4 magnetic nanoparticles (Fe3O4@Ppy) were prepared and used for the extraction of antidepressants. After extraction, the Fe3O4@Ppy with trapped antidepressants was then directly subjected to DCBI-MS analysis with the aid of a homemade magnetic glass capillary. As the MSPE process is rapid and the direct DCBI-MS analysis does not need solvent desorption or chromatographic separation processes, the overall analysis can be completed within 3 min. The proposed MSPE-DCBI-MS method was then successfully used to determine antidepressants in human urine and plasma. The calibration curves were obtained in the range of 0.005-0.5 μg mL(-1) for urine and 0.02-1 μg mL(-1) for plasma with reasonable linearity (R(2) > 0.951). The limits of detection of three antidepressants were in the range of 0.2-1 ng mL(-1) for urine and 2-5 ng mL(-1) for plasma. Acceptable reproducibility for rapid analysis was achieved with relative standard deviations less than 19.1% and the relative recoveries were 85.2-118.7%. Taken together, the developed MSPE-DCBI-MS strategy offers a powerful capacity for rapid analysis of target compounds in a complex matrix, which would greatly expand the applications of ambient ionization techniques with plentiful magnetic sorbents.

Antidepressants: MedlinePlus Health Topic

MedlinePlus

... Your doctor can prescribe them for you. They work to balance some of the natural chemicals in our brains. It may take several weeks for them to help. There are several types of ... finding what works best for you. Antidepressants may cause mild side ...

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

PubMed

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

2015-06-01

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

Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker.

PubMed

Ampuero, Estibaliz; Luarte, Alejandro; Santibañez, Marcos; Varas-Godoy, Manuel; Toledo, Jorge; Diaz-Veliz, Gabriela; Cavada, Gabriel; Rubio, F Javier; Wyneken, Ursula

2015-03-26

Clinically depressed individuals respond to different types of antidepressants, suggesting that different neurobiological mechanisms may be responsible for their depression. However, animal models to characterize this are not yet available. We induced depressive-like behaviors in rats using 2 different chronic stress models: restraint in small cages or immobilization in adaptable plastic cones. Both models increased anxiety responses evaluated by novelty-suppressed feeding and the elevated plus-maze; increased learned helplessness evaluated by the tail suspension and forced swimming tests; and increased anhedonia evaluated by the sucrose preference test. We assessed the ability of 2 different types of antidepressants to ameliorate depressive-like behaviors. We administered the serotonin reuptake inhibitor fluoxetine or the noradrenaline reuptake inhibitor reboxetine once daily for 28 days to rats that received either chronic restraint or immobilization stress, or no stress. Behavioral analysis revealed that fluoxetine ameliorated depressive-like behaviors when induced by chronic restraint stress, whereas reboxetine ameliorated these behaviors when induced by chronic immobilization stress. To further test biological differences between both models, we evaluated the levels of Aldolase C, an enzyme expressed by forebrain astrocytes that is regulated by antidepressant treatment, in the cerebrospinal fluid: chronic restraint stress, but not immobilization stress, increased the levels of Aldolase C. Moreover, the presence of astrocyte-derived Aldolase C-GFP in the cerebrospinal fluid indicates its central origin. Two stress paradigms induced depressive-like behaviors that were sensitive to different antidepressant treatments. Biomarkers such as Aldolase C could help determine optimal antidepressant treatments for clinically depressed patients. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Guidelines on treatment of perinatal depression with antidepressants: An international review

PubMed Central

Kamperman, Astrid M; Boyce, Philip; Bergink, Veerle

2018-01-01

Objective: Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice. Methods: An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients. Results: Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines. Conclusion: During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged. PMID:29506399

Guidelines on treatment of perinatal depression with antidepressants: An international review.

PubMed

Molenaar, Nina M; Kamperman, Astrid M; Boyce, Philip; Bergink, Veerle

2018-04-01

Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice. An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients. Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines. During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.

Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011.

PubMed

Schröder, Carsten; Dörks, Michael; Kollhorst, Bianca; Blenk, Tilo; Dittmann, Ralf W; Garbe, Edeltraut; Riedel, Oliver

2017-02-01

Recent studies on the utilization of antidepressant drugs in minors are scarce, methodologically limited, and do not factor in off-label use sufficiently. Beyond that, little is known about the short treatment durations that have been observed for many young antidepressant users. The present study examined antidepressant use in pediatric patients aged 0 to 17 years over time, investigated changes regarding the prescribed drugs, analyzed underlying diagnoses, and assessed the rate of off-label use. We used claims data of roughly two million individuals to calculate annual prevalence and incidence rates of antidepressant prescriptions for the years 2004 to 2011. Analyses were stratified by age, sex, and drug type. For antidepressant users, numbers of prescriptions, frequencies of disorders/diseases, and specialties of the prescribing physicians were examined. The share of off-label prescriptions was calculated for each year. The prescription prevalence of antidepressants ranged between 1.7 and 2.1 per 1000 minors. The use of tricyclic antidepressants decreased from 0.9 to 0.6 prescriptions per 1000 minors, while the use of selective serotonin reuptake inhibitors increased from 0.5 to 1.1. Of the patients with an antidepressant prescription, 46.4% only received one prescription. Depression was by far the most frequent diagnosis among all antidepressant users as well as among subjects with only one prescription. In 2011, 36.3% of all prescriptions were off-label. The high proportion of single prescriptions, even in patients with a diagnosed depression, and the high rate of off-label use are particularly noteworthy and should be further investigated in future studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

ERIC Educational Resources Information Center

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

2006-01-01

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

[Antidepressant and tolerance: Determinants and management of major side effects].

PubMed

David, D J; Gourion, D

2016-12-01

Antidepressant therapy aims to reach remission of depressive symptoms while reducing the complications and risks of relapse. Even though they have proven their efficacy, it takes several weeks for antidepressants to demonstrate full effectiveness, and adverse effects occur more quickly or (quicker) which can be a source of poor compliance. This latest aspect often leads to dose reduction and/or change of molecule that have the effect of delaying remission. This review attempts to present, from the pharmacological properties of the major classes of antidepressants (monoamine oxidase inhibitor [MAOI], tricyclic antidepressants [TCA], selective serotonin reuptake inhibitor [SSRI] and serotonin and noradrenaline reuptake inhibitor [SNRI]), to the pharmacological mechanisms involved in adverse effects by focusing on sexual dysfunction, nausea/vomiting, and weight changes and sleep disruption. If the activation of dopamine D 1/2  or norepinephrine receptors through the autonomic nervous system controls and facilitates sexual desire, increasing serotoninergic transmission through 5-HT 1B/2A/2C receptors activation inhibits this process. The pharmacological properties of drugs inducing nausea/vomiting activate opiate receptors μ, increase dopaminergic and serotoninergic transmission activating the dopamine D 2  and serotonin 5-HT 3  receptors, respectively. Among the causes responsible for weight gain under antidepressant therapy, monoamine neurotransmission still plays an important role. The blockade of serotonin 5-HT 2C or histamine H 1  receptors is directly responsible for weight gain. Finally, the activation of 5-HT 1A/1B/3/7 serotoninergique receptors modulates wakefulness, raid eyes movement or sleep duration. In conclusion, if antidepressant activity of SERT or MAO inhibitors is an indirect consequence of postsynaptic 5-HT, DA, NA receptor activation, it is also responsible for side effects, causes of poor compliance and hence therapeutic failures. Finally, we

Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates.

PubMed

Estévez-Calvar, Noelia; Canesi, Laura; Montagna, Michele; Faimali, Marco; Piazza, Veronica; Garaventa, Francesca

2017-07-01

Widespread contamination of coastal environments by emerging compounds includes low concentrations of pharmaceuticals. These pollutants are not currently incorporated in monitoring programs despite their effects on non-target organisms are very little documented. Among the selective serotonin reuptake inhibitor (SSRI) antidepressants, sertraline (SRT) is one of the most prescribed globally. In this work, earlier life stages of Amphibalanus amphitrite, Brachionus plicatilis and Mytilus galloprovincialis were exposed to environmental concentrations of SRT in order to study both sub-lethal and lethal responses in 24/48 h-tests. Low concentrations of SRT altered significantly swimming behavior in A. amphitrite and B. plicatilis giving 48 h-EC 50 (μg/L) of 113.88 and 282.23, respectively whereas higher values were observed for mortality and immobilization. EC 50 embryotoxicity with M. galloprovincialis was 206.80 μg/L. This work add new data about SRT ecotoxicity on marine invertebrates and confirms the applicability of behavioral endpoints to evaluate the environmental impact of antidepressants in marine organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

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. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Changing epidemiology of intentional antidepressant drug overdose in Victoria, Australia.

PubMed

Wong, Anselm; Taylor, David McD; Ashby, Karen; Robinson, Jeff

2010-08-01

To determine the epidemiology of intentional antidepressant drug overdose (OD), over an extended time period, in Victoria, Australia. Retrospective epidemiological study of all cases reported to the Victorian Emergency Minimum Dataset (VEMD) January 1998 to December 2007 and calls to the Victorian Poisons Information Centre (VPIC) June 2005 to September 2008. 5467 VEMD cases were analysed. 3169 (57.9%) cases involved selective serotonin reuptake inhibitors (SSRIs) and 1149 (21%) involved tricyclic antidepressants (TCAs). Sertraline (1252, 22.9% cases) was the most common drug. During 2001, the peak year of OD, there were 8.8 OD/100 000 population in the SSRI group and 3.8 OD/100 000 population in the TCA group. Trends over the study period showed increasing SSRI and 'other' newer antidepressant prescription rates and decreases for TCA and monoamine oxidase inhibitors (MAOI). However, the risks of OD in all drug classes were similar and OD/100 000 prescriptions trended downwards for all drug classes over time. 1833 VPIC calls were analysed. Calls relating to SSRIs were the most common yet SSRI OD was associated with significantly fewer symptoms (p < 0.001) and fewer patients with Poisoning Severity Score classifications of moderate or severe (p < 0.01). Antidepressant OD patterns are changing. Antidepressant OD incidence is following prescribing trends. The risk of OD is similar for all drug classes. Absolute numbers of OD and OD/100 000 prescriptions are decreasing for all drug classes.

The identification of depression and the coverage of antidepressant drug prescriptions in Italian general practice.

PubMed

Bellantuono, Cesario; Mazzi, Maria Angela; Tansella, Michele; Rizzo, Raffaella; Goldberg, David

2002-10-01

Studies on antidepressant prescriptions in general practice need to assess the level of prescriptions relative to the need for them ('coverage'), and the variability among doctors. Two different cut-off scores on a screening test for depression (the Personal Health Questionnaire, PHQ) are used to predict rates for depression, and rates for depressive patients thought likely to benefit from antidepressants (according to a severity criterion) in primary care patients. These two rates are compared with assessments by 11 GPs of recognised depression, as well as with rates of drug prescribed. The rate for depression thought likely to be treated with antidepressants estimated with the PHQ is broadly comparable with the rate for conspicuous depressive illness, and much lower than that predicted by the PHQ for depression. There was great variability between GPs in their ability to detect depression, and their preparedness to prescribe antidepressants. Antidepressants were only prescribed for 3.5% of the patients, compared to the 8.9% thought to need them. However, antidepressants, mostly SSRIs, are much more likely to be prescribed than tranquillisers. The limitations of the study are that the PHQ is able to estimate 'coverage' but not 'focusing' (the proportion of those receiving antidepressants who needed them). Although the rate for conspicuous depression is similar to that for depressions thought to be treated with antidepressants, the 'coverage' of antidepressants was only 39.3%. The variability between physicians confirm the need of good practice guidelines and training packages for the identification and management of depression. Large epidemiological studies are needed to overcome the current lack of clinically relevant data on the quality of antidepressant prescriptions in general practice.

[Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

PubMed

Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

2015-12-01

To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity.

PubMed

Jensen-Otsu, Elsbeth; Austin, Gregory L

2015-11-20

Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09-2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use.

Antidepressant Use is Associated with Increased Energy Intake and Similar Levels of Physical Activity

PubMed Central

Jensen-Otsu, Elsbeth; Austin, Gregory L.

2015-01-01

Antidepressants have been associated with weight gain, but the causes are unclear. The aims of this study were to assess the association of antidepressant use with energy intake, macronutrient diet composition, and physical activity. We used data on medication use, energy intake, diet composition, and physical activity for 3073 eligible adults from the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Potential confounding variables, including depression symptoms, were included in the models assessing energy intake, physical activity, and sedentary behavior. Antidepressant users reported consuming an additional (mean ± S.E.) 215 ± 73 kcal/day compared to non-users (p = 0.01). There were no differences in percent calories from sugar, fat, or alcohol between the two groups. Antidepressant users had similar frequencies of walking or biking, engaging in muscle-strengthening activities, and engaging in moderate or vigorous physical activity. Antidepressant users were more likely to use a computer for ≥2 h/day (OR 1.77; 95% CI: 1.09–2.90), but TV watching was similar between the two groups. These results suggest increased energy intake and sedentary behavior may contribute to weight gain associated with antidepressant use. Focusing on limiting food intake and sedentary behaviors may be important in mitigating the weight gain associated with antidepressant use. PMID:26610562

Antidepressants differentially affect striatal amphetamine-stimulated dopamine and serotonin release in rats with high and low novelty-oriented behaviour.

PubMed

O'Leary, Aet; Kõiv, Kadri; Raudkivi, Karita; Harro, Jaanus

2016-11-01

In the studies of depression pathogenesis and antidepressant action, the monoaminergic hypothesis of depression has mainly focused on the serotonergic and noradrenergic mechanisms. However, dopaminergic neurotransmission is also linked to both depressive symptomatology as well as antidepressant effects. We have previously shown that persistent inter-individual differences in the rat behavioural activity in novel environments is associated with differences in the striatal extracellular levels of dopamine and serotonin, depressive-like behaviour and the expression of several depression-related genes. The aim of the current study was to investigate the relative potency of the tricyclic antidepressant imipramine, the selective serotonin re-uptake inhibitor fluoxetine, and the selective noradrenaline re-uptake inhibitor reboxetine (all drugs administered in the dose of 10mg/kg, i.p.) to enhance amphetamine-stimulated dopamine and serotonin release in the striatum using in vivo microdialysis in awake, freely-moving rats, categorized into high explorers (HE) and low explorers (LE) based on their spontaneous novelty-oriented behaviour. The basal extracellular dopamine and serotonin concentration in the striatum did not differ between the LE- and HE-rats. None of the antidepressants alone were able to modify baseline striatal dopamine levels, but the amphetamine-stimulated dopamine release was significantly higher in the HE-rats after acute and chronic imipramine (but not fluoxetine or reboxetine). Acute imipramine and fluoxetine, but not reboxetine, increased both the basal and amphetamine-stimulated levels of serotonin in the striatum. Again, the HE-rats had higher amphetamine-stimulated serotonin release after fluoxetine administration. These findings suggest that rats with depressive-like phenotype are less sensitive to the neurochemical effects of antidepressants in the striatum. These results may have relevance in understanding the neurobiological bases for inter

Maternal Antidepressant Use During Pregnancy and the Risk of Attention-Deficit/Hyperactivity Disorder in Children: A Systematic Review of the Current Literature.

PubMed

Uguz, Faruk

2018-06-01

This study reviewed the current literature examining the potential relationship between use of antidepressants during pregnancy and attention-deficit/hyperactivity disorder (ADHD) in children. PubMed was searched for English language reports between January 1, 1995, and July 31, 2017, by using combinations of the key words pregnancy, antidepressants, selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), children, offspring, and ADHD. Studies that reported association between ADHD in children and use of antidepressant in pregnant women were included in the review. A total of 7 relevant studies that met the review criteria were examined. The studies reported that compared with nonusers adjusted risks of ADHD in children were 1.2 to 1.6 for the use of any antidepressant, 0.91 to 1.66 for selective serotonin reuptake inhibitors, 1.1 to 1.4 for selective serotonin-norepinephrine reuptake inhibitors, and 1.1 to 1.8 for tricyclic antidepressants. There was some scientific evidences suggesting a connection between antidepressant use during all trimesters of pregnancy and increased risk of ADHD in children. In addition, the study results suggest that underlying maternal anxiety or depressive disorders may also contribute to increased risk of ADHD. Although some studies have suggested a moderately increased risk of ADHD in children with maternal antidepressant use during pregnancy, based on limitations and results of the studies, this review concluded that there is no strong evidence to suggest a causal link.

Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects.

PubMed

Al-Samhari, Marwa M; Al-Rasheed, Nouf M; Al-Rejaie, Salim; Al-Rasheed, Nawal M; Hasan, Iman H; Mahmoud, Ayman M; Dzimiri, Nduna

2016-03-01

Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation. Male Wistar rats were subjected to forced swimming test and given N-acetylcysteine and fluoxetine immediately after the pre-test session, 5 h later and 1 h before the test session of the forced swimming test. N-acetylcysteine decreased immobility time (P < 0.05), serum corticosterone (P < 0.001), and hydrogen peroxide (P < 0.001), while restored glutathione concentration. Treatment of the rats with N-acetylcysteine produced significant (P < 0.001) down-regulation of STAT3 mRNA expression and protein phosphorylation. On the other hand, N-acetylcysteine significantly (P < 0.001) increased SOCS3 gene expression; however, SOCS3 protein was not changed. In conclusion, our study suggests that modulation of the JAK/STAT pathway might mediate the antidepressant-like effects of N-acetylcysteine. Therefore, depression research may target the JAK/STAT signaling pathway to provide a novel effective therapy. © 2015 by the Society for Experimental Biology and Medicine.

Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects

PubMed Central

Al-Samhari, Marwa M; Al-Rasheed, Nouf M; Al-Rejaie, Salim; Al-Rasheed, Nawal M; Hasan, Iman H; Dzimiri, Nduna

2015-01-01

Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation. Male Wistar rats were subjected to forced swimming test and given N-acetylcysteine and fluoxetine immediately after the pre-test session, 5 h later and 1 h before the test session of the forced swimming test. N-acetylcysteine decreased immobility time (P < 0.05), serum corticosterone (P < 0.001), and hydrogen peroxide (P < 0.001), while restored glutathione concentration. Treatment of the rats with N-acetylcysteine produced significant (P < 0.001) down-regulation of STAT3 mRNA expression and protein phosphorylation. On the other hand, N-acetylcysteine significantly (P < 0.001) increased SOCS3 gene expression; however, SOCS3 protein was not changed. In conclusion, our study suggests that modulation of the JAK/STAT pathway might mediate the antidepressant-like effects of N-acetylcysteine. Therefore, depression research may target the JAK/STAT signaling pathway to provide a novel effective therapy. PMID:26643864

Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern.

PubMed

Chee, K Y; Tripathi, A; Avasthi, A; Chong, M Y; Xiang, Y T; Sim, K; Kanba, S; He, Y L; Lee, M S; Chiu, H F K; Yang, S Y; Kuga, H; Udomratn, P; Tanra, A J; Maramis, M M; Grover, S; Mahendran, R; Kallivayalil, R A; Shen, W W; Shinfuku, N; Tan, C H; Sartorius, N

2016-03-01

Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia. The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed. A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults. Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

PubMed

Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

2011-04-01

The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that

Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths.

PubMed

Burcu, Mehmet; Zito, Julie M; Safer, Daniel J; Magder, Laurence S; dosReis, Susan; Shaya, Fadia T; Rosenthal, Geoffrey L

2017-12-01

Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment-emergent risk of type 2 diabetes among youths. To assess the association between antidepressant use and the risk of incident type 2 diabetes in youths by antidepressant subclass and according to duration of use, cumulative dose, and average daily dose. A retrospective cohort study was conducted using Medicaid claims data from 4 geographically diverse, large states of youths 5 to 20 years of age who initiated antidepressant treatment from January 1, 2005, to December 31, 2009. Antidepressant use (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic or other cyclic antidepressants, and other antidepressants) was assessed using the following 4 time-varying measures: current or former use, duration of use, cumulative dose, and average daily dose. Incident type 2 diabetes was assessed using discrete-time failure models, adjusting for disease risk score estimated using more than 125 baseline and time-dependent covariates. In this cohort of 119 608 youths aged 5 to 20 years who initiated antidepressant treatment (59 087 female youths and 60 521 male youths; 54.7% between 5 and 14 years of age) with a mean follow-up of 22.8 months, 79 285 [66.3%] had SSRI or SNRI exposure. The risk of type 2 diabetes was significantly greater during current use than former use of SSRIs or SNRIs (absolute risk, 1.29 per 10 000 person-months vs 0.64 per 10 000 person-months; adjusted relative risk [RR], 1.88; 95% CI, 1.34-2.64) and tricyclic or other cyclic antidepressants (absolute risk, 0.89 per 10 000 person-months vs 0.48 per 10 000 person-months; RR, 2.15; 95% CI, 1.06-4.36), but not of other antidepressants (absolute risk, 1

Drug-drug interactions involving antidepressants: focus on desvenlafaxine.

PubMed

Low, Yvette; Setia, Sajita; Lima, Graca

2018-01-01

Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug-drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions.

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)

Beliefs of people taking antidepressants about the causes of their own depression.

PubMed

Read, John; Cartwright, Claire; Gibson, Kerry; Shiels, Christopher; Magliano, Lorenza

2015-03-15

The beliefs of people receiving treatment about the causes of their own mental health problems are researched less often than the causal beliefs of the public, but have important implications for relationships with prescribers, treatment choices and recovery. An online survey on a range of beliefs about depression, and experiences with antidepressants, was completed by 1829 New Zealand adults prescribed anti-depressants in the preceding five years, 97.4% of whom proceeded to take antidepressants. Six of 17 beliefs about the causes of their own depression were endorsed by more than half the sample: chemical imbalance, family stress, work stress, heredity, relationship problems and distressing events in childhood. There were some marked differences in content, structure and level of conviction of beliefs about one׳s own depression and the sample׳s previously published beliefs about depression in general. There were also significant differences between the beliefs of demographic groupings. Regression analyses revealed that self-reported effectiveness of the antidepressants was positively associated with bio-genetic causal beliefs. The quality of the relationship with the prescribing doctor was positively related to a belief in chemical imbalance as a cause and negatively related to a belief in unemployment as a cause. The convenience sample may have been biased towards a favourable view of bio-genetic explanations, since 83% reported that the medication reduced their depression. People experiencing depression hold complex, multifactorial and idiosyncratic sets of beliefs about the causes of their own depression, apparently based at least in part on their own life experiences and circumstances. Exploring those beliefs may enhance the doctor-patient relationship and selection of appropriate treatment modality. Copyright © 2014 Elsevier B.V. All rights reserved.

Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Wenhui

Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokinemore » gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6 h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10 ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life. - Highlights: • Three different antidepressants all have

Patterns and predictors of antidepressant use in ambulatory cancer patients with common solid tumors.

PubMed

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

2015-05-01

Depressive symptoms and antidepressant use are prevalent among cancer patients. We sought to identify determinants of prescribing commonly used antidepressants. This multi-institutional study enrolled 3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or lung. Five case-finding methods were used to identify patients with depressive symptoms. Logistic models were used to examine factors that impact antidepressant use. Approximately, 47% of patients were defined as having depressive symptoms. Clinicians rated being sad/depressed as one of the top three priority problems for 10.5% of patients. Antidepressants were prescribed in 19% of all patients, 25% with depressive symptoms and 14% nondepressed patients. After adjusting for other covariates, these variable categories were significantly associated with greater use of antidepressants: depressive symptoms, family history of depression, concurrent medication use, cancer treatment status, and certain other clinical and demographic variables. The strongest individual predictors were concurrent use of more than 10 medications (odds ratio [OR] = 3.3), a family history of depression (OR = 2.2), sedative use (OR = 2.1), non-Hispanic white race (OR = 2.0), and anxiolytics use (OR = 2.0). Depressive symptoms are found in nearly half of outpatients with cancer, and one-fourth of patients with depressive symptoms are taking an antidepressant. Patients receiving antidepressants are more often those taking multiple medications, those with a depression diathesis, and those with more extensive cancer treatment. Patients who were younger, white, and female were also more likely to be taking antidepressants. Copyright © 2014 John Wiley & Sons, Ltd.

Potential antidepressant overtreatment associated with office use of brief depression symptom measures.

PubMed

Jerant, Anthony; Kravitz, Richard L; Fernandez Y Garcia, Erik; Feldman, Mitchell D; Cipri, Camille; Nishio, Denyse; Knoepfler, Anca; Wooddell, M Kaleo; Baquero, Victor; Franks, Peter

2014-01-01

Use of brief depression symptom measures for identifying or screening cases may help to address depression undertreatment, but whether it also leads to diagnosis and treatment of patients with few or no symptoms-a group unlikely to have major depression or benefit from antidepressants-is unknown. We examined the associations of use of a brief depression symptom measure with depression diagnosis and antidepressant recommendation and prescription among patients with few or no depression symptoms. We conducted exploratory observational analyses of data from a randomized trial of depression engagement interventions conducted in primary care offices in California. Analyses focused on participants scoring <10 on a study-administered 9-item Patient Health Questionnaire (PHQ-9) (completed immediately before an office visit and not disclosed to the provider) with complete chart review data (n = 595). We reviewed visit notes for evidence of practice administration of a brief symptom measure (independent of the trial) and whether the provider (1) diagnosed depression or (2) recommended and/or prescribed an antidepressant. Among the 545 patients without a practice-administered measure, 57 (10.5%) had a visit diagnosis of depression; 9 (1.6%) were recommended and another 21 (3.8%) prescribed an antidepressant. Among the 50 patients (8.4% of total sample) with a practice-administered measure, 10 (20%) had a visit diagnosis of depression; 6 (12%) were recommended and another 6 (12%) prescribed an antidepressant. Adjusting for nesting within providers, trial intervention, stratification variables, and sample weighting, use of a brief symptom measure was associated with depression diagnosis (adjusted odds ratio, 3.2; 95% confidence interval, 1.1-9.2) and antidepressant recommendation and/or prescription (adjusted odds ratio, 3.80; 95% confidence interval, 1.0-13.9). Analyses using progressively lower PHQ-9 thresholds (<9 to <5) and examining antidepressant prescription alone

Impaired heart rate variability and altered cardiac sympathovagal balance after antidepressant overdose.

PubMed

Waring, W S; Rhee, J Y; Bateman, D N; Leggett, G E; Jamie, H

2008-11-01

Antidepressant overdose may be associated with significant cardiotoxicity, and recent data have shown that acute toxic effects are associated with impaired heart rate variability. This study was designed to examine the feasibility of non-invasive heart rate variability recording in patients that present to hospital after deliberate antidepressant ingestion. This was a prospective study of 72 consecutive patients attending the Emergency Department after deliberate antidepressant overdose and 72 age-matched patients that ingested paracetamol, as a control group. Single time-point continuous electrocardiographic recordings were used to allow spectral analyses of heart rate variability determined in low-frequency (LF) and high-frequency (HF) domains. The LF:HF ratio was used to represent overall sympathovagal cardiac activity. Antidepressant overdose was associated with reduced overall heart rate variability: 1329 vs. 2018 ms(2) (P = 0.0239 by Mann-Whitney test). Variability in the LF domain was higher (64.8 vs. 49.8, P = 0.0006), whereas that in the HF domain was lower (24.3 vs. 36.4, P = 0.0001), and the LF:HF ratio was higher in the antidepressant group (2.4 vs. 1.2, P = 0.0003). Antidepressant overdose is associated with impaired heart rate variability in a pattern consistent with excess cardiac sympathetic activity. Further work is required to establish the significance of these findings and to explore whether the impairment of heart rate variability may be used to predict the development of arrhythmia in this patient group.

Antidepressants for depression in patients with dementia: a review of the literature.

PubMed

Leong, Christine

2014-04-01

To evaluate the literature investigating the efficacy and safety of antidepressants for treating depression in individuals with dementia. A literature search was conducted using MEDLINE, PUBMED, EMBASE, and Cochrane databases from inception to May 2013 for studies in English that evaluated the treatment of depression in patients with dementia. All relevant randomized controlled trials (RCTs) and meta-analyses were identified using the search terms "dementia" or "Alzheimer's disease," and "depression" or "major depressive disorder." Reference lists from retrieved articles and practice guidelines were also searched for relevant literature. Only randomized, placebo-controlled trials and meta-analyses that compared an antidepressant with placebo for the treatment of depression in patients with dementia were included. In this systematic review, 10 RCTs and 3 meta-analyses were identified that examined the efficacy and safety of antidepressants compared with placebo in treating depression in patients with dementia. The majority of the RCTs consisted of a small sample size, and the antidepressants studied were not routinely used in practice. The evidence for antidepressants in the treatment of depression in patients with dementia is inconclusive. The accumulation of evidence suggests nonpharmacologic approaches and watchful waiting be attempted for the first 8 to 12 weeks in a patient who presents with both mild-to-moderate depression and dementia. In cases of severe depression, or depression not managed through nonpharmacologic means, a trial of an antidepressant may be initiated. However, further well-designed trials are needed to support these recommendations.

Correlation of antidepressive agents and the mortality of end-stage renal disease.

PubMed

Tsai, Chia-Jui; Loh, El-Wui; Lin, Ching-Heng; Yu, Tung-Min; Chan, Chin-Hong; Lan, Tsuo-Hung

2012-05-01

Depression is one of the most common psychological disorders in end-stage renal disease (ESRD) patients and is associated with impaired quality of life and increased mortality and rate of hospitalization. We aimed to examine the contributions of depression and the use of antidepressive agents in the mortality of ESRD patients. A retrospective observatory study was conducted using the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed as ESRD during the year 2001 to 2007 were collected. A total of 2312 ESRD patients were identified in the database. Statistical analyses were conducted to examine the contributions of depression and exposure of antidepressive agents in mortality rates of ESRD patients. Diagnosis of depression did not influence mortality rate (mortality rate in patients with depression: 26.5%; mortality rate in patients without depression: 26.2%; P= 1.000). Those who had antidepressive agents exposure had significantly higher mortality rate (mortality rate: 32.3%) than those who did not (mortality rate: 24.5%) (P < 0.001). Our findings suggest that (i) the mortality rate of ESRD patients was not affected by the diagnosis of depression, and (ii) exposure of antidepressive agents in ESRD patients was associated with a higher mortality rate. The high mortality rate in ESRD patients exposed to antidepressive agents can be a bias by indication. Equally, a true contribution of the antidepressive agents cannot be ruled out and this needs clarification. © 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.

Theoretical Approaches to Enhancing Motivation for Adherence to Antidepressant Medications.

PubMed

Hamrin, Vanya; Sinclair, Vaughn G; Gardner, Virginia

2017-04-01

Adherence to antidepressants is a major challenge in our health care system, with a high percentage of patients discontinuing their medications within six months. The purpose of this position paper is to discuss theoretical frameworks that address the psychological beliefs, benefits and barriers and feelings of autonomy that affect a person's willingness and motivation to take anti-depressant medications within a therapeutic relationship with a nurse practitioner. Three theoretical frameworks were selected to highlight particular perspectives relevant to enhancing patient motivation for medication adherence. The Self-Regulation Model, Health Belief Model, and Self-Determination Theory combined with motivational interviewing all offer guidance on strategies for improving adherence to antidepressants. The Self-Regulation Model underscores the importance of illness representations that prompt considering patient perceptions of depression that affect adherence. The Health Belief Model focuses on cost-benefit considerations that affect patient's adherence, along with perceived control. Finally, Self-Determination Theory combined with motivational interviewing offers strategies that enhance autonomy and optimize collaboration and motivation for adherence. These three theoretical models are applied to a vignette for a patient who is having difficulty with adherence to antidepressant medication. Copyright © 2016 Elsevier Inc. All rights reserved.

Beliefs about medications predict adherence to antidepressants in older adults.

PubMed

Fawzi, Waleed; Abdel Mohsen, Mohamed Yousry; Hashem, Abdel Hamid; Moussa, Suaad; Coker, Elizabeth; Wilson, Kenneth C M

2012-01-01

Adherence to treatment is a complex and poorly understood phenomenon. This study investigates the relationship between older depressed patients' adherence to antidepressants and their beliefs about and knowledge of the medication. Assessment was undertaken of 108 outpatients over the age of 55 years diagnosed with depressive disorder and treated for at least four weeks with antidepressants. Adherence was assessed using two self-report measures: the Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM). Potential predictors of adherence investigated included sociodemographic, medication and illness variables. In addition, 33 carers were interviewed regarding general medication beliefs. 56% of patients reported 80% or higher adherence on the GAM. Sociodemographic variables were not associated with adherence on the MARS. Specific beliefs about medicines, such as "my health depends on antidepressants" (necessity) and being less worried about becoming dependant on antidepressants (concern) were highly correlated with adherence. General beliefs about medicines causing harm or being overprescribed, experiencing medication side-effects and severity of depression also correlated with poor adherence. Linear regression with the MARS as the dependent variable explained 44.3% of the variance and showed adherence to be higher in subjects with healthy specific beliefs who received more information about antidepressants and worse with depression severity and autonomic side-effects. Our findings strongly support a role for specific beliefs about medicines in adherence. Challenging patients' beliefs, providing information about treatment and discussing side-effects could improve adherence. Poor response to treatment and medication side-effects can indicate poor adherence and should be considered before switching medications.

BIDIRECTIONAL PROSPECTIVE ASSOCIATIONS OF METABOLIC SYNDROME COMPONENTS WITH DEPRESSION, ANXIETY, AND ANTIDEPRESSANT USE

PubMed Central

Révész, Dóra; Lamers, Femke; Giltay, Erik; Penninx, Brenda W. J. H.

2016-01-01

Background Metabolic syndrome components—waist circumference, high‐density lipoprotein cholesterol (HDL‐C), triglycerides, systolic blood pressure and fasting glucose—are cross‐sectionally associated with depression and anxiety with differing strength. Few studies examine the relationships over time or whether antidepressants have independent effects. Methods Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2,776; 18–65 years; 66% female). At baseline, 2‐ and 6‐year follow‐up, participants completed diagnostic interviews, depression and anxiety symptom inventories, antidepressant use assessment, and measurements of the five metabolic syndrome components. Data were analyzed for the consistency of associations between psychopathology indicators and metabolic syndrome components across the three assessment waves, and whether psychopathology or antidepressant use at one assessment predicts metabolic dysregulation at the next and vice versa. Results Consistently across waves, psychopathology was associated with generally poorer values of metabolic syndrome components, particularly waist circumference and triglycerides. Stronger associations were observed for psychopathology symptom severity than diagnosis. Antidepressant use was independently associated with higher waist circumference, triglycerides and number of metabolic syndrome abnormalities, and lower HDL‐C. Symptom severity and antidepressant use were associated with subsequently increased number of abnormalities, waist circumference, and glucose after 2 but not 4 years. Conversely, there was little evidence that metabolic syndrome components were associated with subsequent psychopathology outcomes. Conclusions Symptom severity and antidepressant use were independently associated with metabolic dysregulation consistently over time and also had negative consequences for short‐term metabolic health. This is of concern given the chronicity of depression and

Antidepressants recruit new neurons to improve stress response regulation

PubMed Central

Surget, A; Tanti, A; Leonardo, E D; Laugeray, A; Rainer, Q; Touma, C; Palme, R; Griebel, G; Ibarguen-Vargas, Y; Hen, R; Belzung, C

2011-01-01

Recent research suggests an involvement of hippocampal neurogenesis in behavioral effects of antidepressants. However, the precise mechanisms through which newborn granule neurons might influence the antidepressant response remain elusive. Here, we demonstrate that unpredictable chronic mild stress in mice not only reduces hippocampal neurogenesis, but also dampens the relationship between hippocampus and the main stress hormone system, the hypothalamo-pituitary-adrenal (HPA) axis. Moreover, this relationship is restored by treatment with the antidepressant fluoxetine, in a neurogenesis-dependent manner. Specifically, chronic stress severely impairs HPA axis activity, the ability of hippocampus to modulate downstream brain areas involved in the stress response, the sensitivity of the hippocampal granule cell network to novelty/glucocorticoid effects and the hippocampus-dependent negative feedback of the HPA axis. Remarkably, we revealed that, although ablation of hippocampal neurogenesis alone does not impair HPA axis activity, the ability of fluoxetine to restore hippocampal regulation of the HPA axis under chronic stress conditions, occurs only in the presence of an intact neurogenic niche. These findings provide a mechanistic framework for understanding how adult-generated new neurons influence the response to antidepressants. We suggest that newly generated neurons may facilitate stress integration and that, during chronic stress or depression, enhancing neurogenesis enables a dysfunctional hippocampus to restore the central control on stress response systems, then allowing recovery. PMID:21537331

Retrospective case series analysis of characteristics and trends in unintentional pharmaceutical drug poisoning by methadone, opioid analgesics, antidepressants and benzodiazepines in Clark County, NV 2009-13.

PubMed

Bruno, Tamara; Pharr, Jennifer R

2017-06-01

Poisoning has become the leading cause of injury death in the USA-with opioid analgesic involved in more fatal poisonings than any other drug, including cocaine and heroin. The epidemic of prescription drug poisonings is a public health concern. This study aimed to define potential high-risk groups for unintentional prescription drug poisoning by methadone, opioid analgesics, antidepressants or benzodiazepines. A hospital-based retrospective case series analysis of admissions related to prescription drug poisonings associated with methadone, opioid analgesics, antidepressants or benzodiazepines for hospitals in Clark County, Nevada between 2009 and 2013 was employed. There were 7414 admissions with a primary diagnosis of an unintentional poisoning due to methadone, opioid analgesics, antidepressants or benzodiazepines. Women had the highest rate of admissions particularly in the 45-54 age group. Higher rates of admissions were also found among non-Hispanic whites, single and uninsured populations. There were concerning increases in admissions among 65+ and Native American/Alaskan Native subgroups in 2013. Benzodiazepines and opioid analgesics were the most prevalent drug categories for prescription drug poisoning admissions. Public health professionals can utilize hospital data to identify populations at risk and in need of targeted interventions. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Agomelatine versus other antidepressive agents for major depression.

PubMed

Guaiana, Giuseppe; Gupta, Sumeet; Chiodo, Debbie; Davies, Simon J C; Haederle, Katja; Koesters, Markus

2013-12-17

Major depressive disorder (MDD), or depression, is a syndrome characterised by a number of behavioural, cognitive and emotional features. It is most commonly associated with a sad or depressed mood, a reduced capacity to feel pleasure, feelings of hopelessness, loss of energy, altered sleep patterns, weight fluctuations, difficulty in concentrating and suicidal ideation. There is a need for more effective and better tolerated antidepressants to combat this condition. Agomelatine was recently added to the list of available antidepressant drugs; it is a novel antidepressant that works on melatonergic (MT1 and MT2), 5-HT 2B and 5-HT2C receptors. Because the mechanism of action is claimed to be novel, it may provide a useful, alternative pharmacological strategy to existing antidepressant drugs. The objective of this review was 1) to determine the efficacy of agomelatine in alleviating acute symptoms of major depressive disorder in comparison with other antidepressants, 2) to review the acceptability of agomelatine in comparison with other antidepressant drugs, and, 3) to investigate the adverse effects of agomelatine, including the general prevalence of side effects in adults. We searched the Cochrane Collaboration's Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 31 July 2013. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 onwards), MEDLINE (1950 onwards) and PsycINFO (1967 onwards). We checked reference lists of relevant studies together with reviews and regulatory agency reports. No restrictions on date, language or publication status were applied to the search. Servier Laboratories (developers of agomelatine) and other experts in the field were contacted for supplemental data. Randomised controlled trials allocating adult participants with major depression to agomelatine versus any

Does exposure to conflict of interest policies in psychiatry residency affect antidepressant prescribing?

PubMed

Epstein, Andrew J; Busch, Susan H; Busch, Alisa B; Asch, David A; Barry, Colleen L

2013-02-01

Academic medical institutions have instituted conflict of interest (COI) policies in response to concerns about pharmaceutical industry influence. To determine whether exposure to COI policies during psychiatry residency training affects psychiatrists' antidepressant prescribing patterns after graduation. We used 2009 physician-level national administrative prescribing data from IMS Health for 1652 psychiatrists from 162 residency programs. We used difference-in-differences estimation to compare antidepressant prescribing based on graduation before (2001) or after (2008) COI policy adoption across residency program groups with maximally, moderately, and minimally restrictive COI policies. The primary outcomes were shares of psychiatrists' prescribing of heavily promoted, brand reformulated, and brand antidepressants. Rates of prescribing heavily promoted, brand reformulated, and brand antidepressants in 2009 were lower among post-COI graduates than pre-COI graduates at all levels of COI restrictiveness. However, differences between pre-COI and post-COI graduates' prescribing of heavily promoted medications were larger for maximally restrictive programs than both minimally restrictive programs [-4.3 percentage points; 95% confidence interval (CI), -7.0, -1.6] and moderately restrictive programs (-3.6 percentage points; 95% CI, -6.2, -1.1). The difference in prescribing reformulations was larger for maximally restrictive programs than minimally restrictive programs (-3.0 percentage points; 95% CI, -5.3, -0.7). Results were consistent for prescribing of brand drugs. This study provides the first empirical evidence of the effects of COI policies. Our results suggest that COI policies can help inoculate physicians against persuasive aspects of pharmaceutical promotion. Further research should assess whether these policies affect other drug classes and physician specialties similarly.

Sertraline versus other antidepressive agents for depression.

PubMed

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

2010-04-14

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. 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. 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. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. 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). 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 in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine

Sertraline versus other antidepressive agents for depression.

PubMed

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

2009-04-15

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. To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. 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. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. 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). 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 in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine

Sertraline versus other antidepressive agents for depression.

PubMed

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

2010-01-20

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. 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. 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. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. 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). 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 in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine

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

[Antidepressant prescription patterns in patients affiliated with the General Social Security Health System of Colombia].

PubMed

Machado-Alba, Jorge E; Morales Plaza, Cristhian David; Solarte Gómez, Mónica Johanna

2011-11-01

Determine patterns of antidepressive drug prescription in a group of patients affiliated with the General Social Security Health System in Colombia. Observational descriptive study of 9 881 patients, of both sexes and older than 5 years of age, medicated with antidepressants and continuously treated from August to October 2009. The patients include residents from 56 Colombian cities. A database was designed based on the consumption of medicines obtained from the company that distributes them to the patients. The average age was 59.1 ± 16.1 years; 73.7% of the participants were women. Of the total number of patients, 83.3% were treated with monotherapy and 16.7% with two or more antidepressants. The order of the prescription of the medicines was: selective serotonin reuptake inhibitors, 47.0%; atypical, 37.8%; tricyclical, 31.8%; selective serotonin reuptake inhibitors and norepinephrine, 1.8%; and selective norepinephrine reuptake inhibitors, 0.03%. The combinations most used were fluoxetine + trazodone (n = 1 029); amitriptyline + fluoxetine (n = 265); amitriptyline + trazodone (n = 122); fluoxetine + imipramine (n = 106); and imipramine + trazodone (n = 71). The most prescribed co-medications were anti-hypertensives (52.3%); thyroid hormones (23.3%); anti-inflammatories (19.6%); anti-epileptics (15.4%); anti-diabetics (13.8%); anti-anxiety and hypnotics (12.4%); antipsychotics (7.4%); anti-Parkinsons (4.3%); and anti-neoplastics (2.2%). The practice of prescribing medicines with a high therapeutic value predominates, mainly for antidepressive monotherapy. Most of the antidepressants are prescribed at dosages lower than those recommended. There is a need to design educational strategies to correct some prescription practices and to conduct research.

Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22.

PubMed

Krause-Heuer, Anwen M; Fraser-Spears, Rheaclare; Dobrowolski, Jeremy C; Ashford, Mark E; Wyatt, Naomi A; Roberts, Maxine P; Gould, Georgianna G; Cheah, Wai-Ching; Ng, Clarissa K L; Bhadbhade, Mohan; Zhang, Bo; Greguric, Ivan; Wheate, Nial J; Kumar, Naresh; Koek, Wouter; Callaghan, Paul D; Daws, Lynette C; Fraser, Benjamin H

2017-09-08

Herein we describe the synthesis and evaluation of antidepressant properties of seven analogues (1-7) of the low affinity/high capacity transporter blocker decynium-22 (D-22). All analogues (1-7) were synthesized via base promoted coupling reactions between N-alkylated-2-methylquinolinium iodides or N-alkylated-4-methylquinolinium iodides and electrophilic N-alkylated-2-iodoquinolinium iodides. All final compounds were purified by re-crystallization or preparative HPLC and initial evaluation studies included; 1) screening for in vitro α1-adrenoceptor activity (a property that can lead to unwanted side-effects), 2) measuring antidepressant-like activity in a mouse tail suspension test (TST), and 3) measuring effects upon mouse locomotion. The results showed some analogues have lower affinities at α1-adrenoceptors compared to D-22 and showed antidepressant-like activity without the need for co-administration of SSRIs. Additionally, many analogues did not affect mouse locomotion to the same extent as D-22. Plans for additional evaluations of these promising analogues, including measurement of antidepressant-like activity with co-administration of selective serotonin re-uptake inhibitors (SSRIs), are outlined. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

PubMed

Nurnberg, H George; Hensley, Paula L

2003-01-01

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

Electrospun fibrous thin film microextraction coupled with desorption corona beam ionization-mass spectrometry for rapid analysis of antidepressants in human plasma.

PubMed

Chen, Di; Hu, Yu-Ning; Hussain, Dilshad; Zhu, Gang-Tian; Huang, Yun-Qing; Feng, Yu-Qi

2016-05-15

Appropriate sample preparations prior to analysis can significantly enhance the sensitivity of ambient ionization techniques, especially during the enrichment or purification of analytes in the presence of complex biological matrix. Here in, we developed a rapid analysis method by the combination of thin film microextraction (TFME) and desorption corona beam ionization (DCBI) for the determination of antidepressants in human plasma. Thin films used for extraction consisted of sub-micron sized highly ordered mesoporous silica-carbon composite fibers (OMSCFs), simply prepared by electrospinning and subsequent carbonization. Typically, OMSCFs thin film was immersed into the diluted plasma for extraction of target analytes and then directly subjected to the DCBI-MS for detection. Size-exclusion effect of mesopores contributed to avoid of the protein precipitation step prior to extraction. Mass transfer was benefited from high surface-to-volume ratio which is attributed to macroporous network and ordered mesostructures. Moreover, the OMSCFs provided mixed-mode hydrophobic/ion-exchange interactions towards target analytes. Thus, the detection sensitivity was greatly improved due to effective enrichment of the target analytes and elimination of matrix interferences. After optimization of several parameters related to extraction performance, the proposed method was eventually applied for the determination of three antidepressants in human plasma. The calibration curves were plotted in the range of 5-1000 ng/mL with acceptable linearity (R(2) >0.983). The limits of detection (S/N=3) of three antidepressants were in ranges of 0.3-1 ng/mL. Reproducibility was achieved with RSD less than 17.6% and the relative recoveries were in ranges of 83.6-116.9%. Taken together, TFME-DCBI-MS method offers a powerful capacity for rapid analysis to achieve much-improved sensitivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Antidepressant Use among Persons Aged 12 and Over: United States, 2011-2014. NCHS Data Brief. Number 283

ERIC Educational Resources Information Center

Pratt, Laura A.; Brody, Debra J.; Gu, Qiuping

2017-01-01

Antidepressants are one of the three most commonly used therapeutic drug classes in the United States. While the majority of antidepressants are taken to treat depression, antidepressants can also be taken to treat other conditions, like anxiety disorders. This Data Brief provides the most recent estimates of antidepressant use in the U.S.…

Antidepressant use during pregnancy: navigating the sea of information.

PubMed

Einarson, Adrienne

2013-09-01

When some of my patients who are taking antidepressants learn they are pregnant, they become anxious and confront me with the following statement: "I need this medication, but have heard so many conflicting stories from my friends and on the Internet and in the media that I am not sure if I should continue taking it." How do I advise them, as I have also seen conflicting evidence in the scientific literature? To date, antidepressants are the most studied drugs during pregnancy, with more than 30 000 outcomes examining increased risks of adverse effects on exposed infants. The results of the studies can appear to be conflicting owing to differing interpretation of statistical analysis and subsequent knowledge transfer and translation of the information. However, there does not appear to be a clinically significant increased risk of any of the adverse outcomes reported in peer-reviewed published studies that would preclude a woman from taking a needed antidepressant during pregnancy.

Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malatynska, E.; Knapp, R.J.; Ikeda, M.

1988-01-01

Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also know that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated /sup 36/Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced bymore » them.« less

The antidepressant effect of running is associated with increased hippocampal cell proliferation.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Brené, Stefan

2005-09-01

A common trait of antidepressant drugs, electroconvulsive treatment and physical exercise is that they relieve depression and up-regulate neurotrophic factors as well as cell proliferation and neurogenesis in the hippocampus. In order to identify possible biological underpinnings of depression and the antidepressant effect of running, we analysed cell proliferation, the level of the neurotrophic factor BDNF in hippocampus and dynorphin in striatum/accumbens in 'depressed' Flinders Sensitive Line rats (FSL) and Flinders Resistant Line (FRL) rats with and without access to running-wheels. The FRL strain exhibited a higher daily running activity than the FSL strain. Wheel-running had an antidepressant effect in the 'depressed' FSL rats, as indicated by the forced swim test. In the hippocampus, cell proliferation was lower in the 'depressed' rats compared to the control FRL rats but there was no difference in BDNF or dynorphin levels in striatum/accumbens. After 5 wk of running, cell proliferation increased in FSL but not in FRL rats. BDNF and dynorphin mRNA levels were increased in FRL but not to the same extent in the in FSL rats; thus, increased BDNF and dynorphin levels were correlated to the running activity but not to the antidepressant effect of running. The only parameter that was associated to basal level of 'depression' and to the antidepressant effect was cell proliferation in the hippocampus. Thus, suppression of cell proliferation in the hippocampus could constitute one of the mechanisms that underlie depression, and physical activity might be an efficient antidepressant.

Antidepressant-like responses in the forced swimming test elicited by glutathione and redox modulation.

PubMed

Rosa, Juliana M; Dafre, Alcir Luiz; Rodrigues, Ana Lúcia S

2013-09-15

Glutathione (GSH) displays a broad range of functions, among them a role as a neuromodulator with some neuroprotective properties. Taking into account that oxidative stress has been associated with depressive disorders, this study investigated the possibility that GSH, a major cell antioxidant, elicits an antidepressant-like effect in mice. Thus, GSH was administered by i.c.v. route to mice that were tested in the forced swimming test and in the tail suspension test, two predictive tests for antidepressant drug activity. In addition, GSH metabolism and the redox environment were modulated in order to study the possible mechanisms underlying the effects of GSH in the forced swimming test. The administration of GSH decreased the immobility time in the forced swimming test (300-3000nmol/site) and tail suspension test (100-1000nmol/site), consistent with an antidepressant-like effect. GSH depletion elicited by l-buthionine sulfoximine (3.2μmol/site, i.c.v.) did not alter the antidepressant-like effect of GSH, whereas the inhibition of extracellular GSH catabolism by acivicin (100nmol/site, i.c.v.) prevented the antidepressant-like effect of GSH. Moreover, a sub-effective dose (0.01nmol/site, i.c.v.) of the oxidizing agent DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) potentiated the effect of GSH (100nmol/site, i.c.v.), while the pretreatment (25-100mg/kg, i.p.) with the reducing agent DTT (dl-dithiothreitol) prevented the antidepressant-like effect of GSH (300nmol/site, i.c.v.). DTNB (0.1nmol/site, i.c.v.), produced an antidepressant-like effect, per se, which was abolished by DTT (25mg/kg, i.p.). The results show, for the first time, that centrally administered GSH produces an antidepressant-like effect in mice, which can be modulated by the GSH metabolism and the thiol/disulfide reagents. The redox environment may constitute a new venue for future antidepressant-drug development. Copyright © 2013 Elsevier B.V. All rights reserved.

Antidepressant use in late gestation and risk of postpartum haemorrhage: a retrospective cohort study.

PubMed

Grzeskowiak, L E; McBain, R; Dekker, G A; Clifton, V L

2016-11-01

To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). Retrospective cohort study. Tertiary teaching hospital in Adelaide, Australia. A total of 30 198 women delivering between 2002 and 2008. Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia. The primary outcome was PPH, defined as a recorded blood loss of ≥500 mL for vaginal deliveries and ≥1000 mL for caesarean sections. Secondary outcomes included severe PPH (≥1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records). Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53; 95% confidence interval, 95% CI 1.25-1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04; 95% CI 0.89-1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84; 95% CI 1.39-2.44), as well as postpartum anaemia (aRR 1.80; 95% CI 1.46-2.22). Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH. Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage. © 2015 Royal College of Obstetricians and Gynaecologists.

Relationship of pharmaceutical promotion to antidepressant switching and adherence: a retrospective cohort study.

PubMed

Hansen, Richard A; Chen, Shih-Yin; Gaynes, Bradley N; Maciejewski, Matthew L

2010-12-01

Patient nonadherence and early discontinuation of antidepressant treatment are common. Pharmaceutical promotion to consumers and physicians may influence this behavior. The objectives of this study were to explore whether promotional spending is related to early antidepressant switching, acute-phase adherence, and continuation-phase adherence. A retrospective cohort study was conducted with national promotional expenditure data merged with medical and prescription claims data from a large national health plan affiliated with i3 Innovus. Included were records for continuously insured adults with major depression who received a new prescription for an antidepressant: 5,010 were in the cohort assessed for switching, 4,457 were in the cohort assessed for acute-phase adherence, and 1,772 were in the cohort assessed for continuation-phase adherence. National promotional efforts were estimated by examining inflation-adjusted spending on direct-to-consumer advertising (DTCA) and physician detailing. Clinical guidelines were used to create proxies for aspects of treatment outcomes, including antidepressant switching and adherence in the acute phase and adherence in the continuation phase. Logistic regression models estimated the association between promotional variables and these outcomes. Patients taking medications that were more highly promoted to physicians were less likely to switch medications (odds ratio [OR]=.61) and were more likely to be adherent during the acute phase of treatment (OR=1.13). DTCA had little effect on switching or antidepressant adherence. Detailing to physicians was associated with lower rates of medication switching and had a positive relationship with patient adherence during early antidepressant treatment. This finding indicates that certain aspects of promotion may have beneficial effects on antidepressant use.

BIDIRECTIONAL PROSPECTIVE ASSOCIATIONS OF METABOLIC SYNDROME COMPONENTS WITH DEPRESSION, ANXIETY, AND ANTIDEPRESSANT USE.

PubMed

Hiles, Sarah A; Révész, Dóra; Lamers, Femke; Giltay, Erik; Penninx, Brenda W J H

2016-08-01

Metabolic syndrome components-waist circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, systolic blood pressure and fasting glucose-are cross-sectionally associated with depression and anxiety with differing strength. Few studies examine the relationships over time or whether antidepressants have independent effects. Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2,776; 18-65 years; 66% female). At baseline, 2- and 6-year follow-up, participants completed diagnostic interviews, depression and anxiety symptom inventories, antidepressant use assessment, and measurements of the five metabolic syndrome components. Data were analyzed for the consistency of associations between psychopathology indicators and metabolic syndrome components across the three assessment waves, and whether psychopathology or antidepressant use at one assessment predicts metabolic dysregulation at the next and vice versa. Consistently across waves, psychopathology was associated with generally poorer values of metabolic syndrome components, particularly waist circumference and triglycerides. Stronger associations were observed for psychopathology symptom severity than diagnosis. Antidepressant use was independently associated with higher waist circumference, triglycerides and number of metabolic syndrome abnormalities, and lower HDL-C. Symptom severity and antidepressant use were associated with subsequently increased number of abnormalities, waist circumference, and glucose after 2 but not 4 years. Conversely, there was little evidence that metabolic syndrome components were associated with subsequent psychopathology outcomes. Symptom severity and antidepressant use were independently associated with metabolic dysregulation consistently over time and also had negative consequences for short-term metabolic health. This is of concern given the chronicity of depression and anxiety and prevalence of antidepressant treatment. © 2016 The

Anxiolytic- and Antidepressant-like Effects of the Methadone Metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP)

PubMed Central

Lee, Bridgin G.; Olson, Thao T.; Xie, Teresa; Xiao, Yingxian; Blendy, Julie A.; Kellar, Kenneth J.

2015-01-01

The enhancement of GABAergic and monoaminergic neurotransmission has been the mainstay of pharmacotherapy and the focus of drug-discovery for anxiety and depressive disorders for several decades. However, the significant limitations of drugs used for these disorders underscores the need for novel therapeutic targets. Neuronal nicotinic acetylcholine receptors (nAChRs) may represent one such target. For example, mecamylamine, a non-competitive antagonist of nAChRs, displays positive effects in preclinical tests for anxiolytic and antidepressant activity in rodents. In addition, nicotine elicits similar effects in rodent models, possibly by receptor desensitization. Previous studies (Xiao et al., 2001) have identified two metabolites of methadone, EMDP (2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline) and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), which are considered to be inactive at opiate receptors, as relatively potent noncompetitive channel blockers of rat α3β4 nAChRs. Here, we show that these compounds are likewise highly effective blockers of human α3β4 and α4β2 nAChRs. Moreover, we show that they display relatively low affinity for opiate binding sites labeled by [3H]-naloxone. We then evaluated these compounds in rats and mice in preclinical behavioral models predictive of potential anxiolytic and antidepressant efficacy. We found that EMDP, but not EDDP, displayed robust effects predictive of anxiolytic and antidepressant efficacy without significant effects on locomotor activity. Moreover, EMDP at behaviorally active doses, unlike mecamylamine, did not produce eyelid ptosis, suggesting it may produce fewer autonomic side effects than mecamylamine. Thus, the methadone metabolite EMDP may represent a novel therapeutic avenue for the treatment of some affective disorders. PMID:26365569

Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice.

PubMed

Burokas, Aurelijus; Arboleya, Silvia; Moloney, Rachel D; Peterson, Veronica L; Murphy, Kiera; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

2017-10-01

The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology. Copyright © 2017 Society of Biological Psychiatry. Published by

Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

PubMed

Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

2010-12-17

Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects. Copyright © 2010 Elsevier B.V. All rights reserved.

The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: significance for the use as anxiolytic/antidepressant drug.

PubMed

Inta, Dragos; Filipovic, Dragana; Lima-Ojeda, Juan M; Dormann, Christof; Pfeiffer, Natascha; Gasparini, Fabrizio; Gass, Peter

2012-04-01

Glutamatergic agents have been conceptualized as powerful, fast-acting alternatives to monoaminergic-based antidepressants. NMDA receptor antagonists such as ketamine or MK-801 are therapeutically effective, but their clinical use is hampered by psychotomimetic effects, accompanied by neurotoxicity in the retrosplenial and cingulate cortex. Antagonists of metabotropic mGlu5 receptors like MPEP elicit both robust antidepressant and anxiolytic effects; however, the underlying mechanisms are yet unknown. mGlu5 receptors closely interact with NMDA receptors, but whether MPEP induces neurotoxicity similar to NMDA receptor antagonists has not been elucidated. We show here using c-Fos brain mapping that MPEP administration results in a restricted activation of distinct stress-related brain areas, including the bed nucleus of stria terminalis (BNST), central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus (PVNH), in a pattern similar to that induced by classical antidepressants and anxiolytics. Unlike the NMDA antagonist MK-801, MPEP does not injure the adult retrosplenial cortex, in which it fails to induce heat shock protein 70 (Hsp70). Moreover, MPEP does not elicit to the same extent as MK-801 apoptosis in cortical areas at perinatal stages, as revealed by caspase 3 expression. These data identify new cellular targets for the anxiolytic and antidepressant effect of MPEP, indicating also in addition that in contrast to MK-801, it lacks the cortical neurotoxicity associated with psychotomimetic side-effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antidepressant sales and regional variations of suicide mortality in Germany.

PubMed

Blüml, Victor; Helbich, Marco; Mayr, Michael; Turnwald, Roland; Vyssoki, Benjamin; Lewitzka, Ute; Hartung, Sebastian; Plener, Paul L; Fegert, Jörg M; Kapusta, Nestor D

2017-04-01

Suicides account for over one million deaths per year worldwide with depression among the most important risk factors. Epidemiological research into the relationship between antidepressant utilization and suicide mortality has shown heterogeneous and contradictory results. Different methodological approaches and limitations could at least partially explain varying results. This is the first study assessing the association of suicide mortality and antidepressant sales across Germany using complex statistical approaches in order to control for possible confounding factors including spatial dependency of data. German suicide counts were analyzed on a district level (n = 402) utilizing ecological Poisson regressions within a hierarchical Bayesian framework. Due to significant spatial effects between adjacent districts spatial models were calculated in addition to a baseline non-spatial model. Models were adjusted for several confounders including socioeconomic variables, quality of psychosocial care, and depression prevalence. Separate analyses were performed for Eastern and Western Germany and for different classes of antidepressants (SSRIs and TCAs). Overall antidepressant sales were significantly negatively associated with suicide mortality in the non-spatial baseline model, while after adjusting for spatially structured and unstructured effects the association turned out to be insignificant. In sub-analyses, analogue results were found for SSRIs and TCAs separately. Suicide risk shows a distinct heterogeneous pattern with a pronounced relative risk in Southeast Germany. In conclusion, the results reflect the heterogeneous findings of previous studies on the association between suicide mortality and antidepressant sales and point to the complexity of this hypothesized link. Furthermore, the findings support tailored suicide preventive efforts within high risk areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of patient experience and its influence on adherence to antidepressant treatment.

PubMed

Johnston, Brenda J

2013-12-01

Major depression can be a very challenging illness and although antidepressant agents are shown to provide benefit, many patients do not adhere to antidepressant treatment guidelines. Multiple factors contribute to adherence, including the influence of patient experience. The purpose of this article is to conduct a systematic review on the influence of patient experience with depression and antidepressant agents on treatment adherence. Thirteen research articles were selected for the review and revealed that patient past experience with depression and antidepressant agents, vicarious experiences, beliefs and attitudes, and the treatment experience itself can impact adherence. It is important for providers to be vigilant with assessment and include patient experience when developing a plan of care. This approach encourages shared decision making and a patient-centered focus for improved management of depression. Copyright 2013, SLACK Incorporated.

Utilization of antihypertensives, antidepressants, antipsychotics, and hormones in Alzheimer disease.

PubMed

Zhu, Carolyn W; Livote, Elayne E; Kahle-Wrobleski, Kristin; Scarmeas, Nikolaos; Albert, Marilyn; Brandt, Jason; Blacker, Deborah; Sano, Mary; Stern, Yaakov

2011-01-01

This study explores the longitudinal relationship between patient characteristics and use of 4 drug classes (antihypertensives, antidepressants, antipsychotics, and hormones) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient/caregiver-reported prescription medication usage was categorized by drug class for 201 patients from the Predictors Study. Patient characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation, baseline age, and sex. Assessment interval, year of study entry, and site were controlled for. Before adjusting for covariates, useage increased for antihypertensives (47.8% to 62.2%), antipsychotics (3.5% to 27.0%), and antidepressants (32.3% to 40.5%); use of hormones decreased (19.4% to 5.4%). After controlling for patient characteristics, effects of time on the use of antidepressants were no longer significant. Antihypertensive use was associated with poorer functioning, concurrent use of memantine, and older age. Antipsychotic use was associated with poorer functioning and poorer cognition. Antidepressant use was associated with younger age, poorer functioning, and concurrent use of cholinesterase inhibitors and memantine. Hormone use was associated with being female and younger age. Findings suggest accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine.

Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis.

PubMed

Ross, Lori E; Grigoriadis, Sophie; Mamisashvili, Lana; Vonderporten, Emily H; Roerecke, Michael; Rehm, Jürgen; Dennis, Cindy-Lee; Koren, Gideon; Steiner, Meir; Mousmanis, Patricia; Cheung, Amy

2013-04-01

Untreated depression during pregnancy has been associated with increased morbidity and mortality for both mother and child and, as such, optimal treatment strategies are required for this population. There are conflicting data regarding potential risks of prenatal antidepressant treatment. To determine whether prenatal antidepressant exposure is associated with risk for selected adverse pregnancy or delivery outcomes. DATA SOURCES MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Library were searched from their start dates to June 30, 2010. STUDY SELECTION English-language studies reporting outcomes associated with pharmacologic treatment during pregnancy were included. We reviewed 3074 abstracts, retrieved 735 articles, and included 23 studies in this meta-analysis. Study design, antidepressant exposure, adjustment for confounders, and study quality were extracted by 2 independent reviewers. There was no significant association between antidepressant medication exposure and spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055). Gestational age and preterm delivery were statistically significantly associated with antidepressant exposure (mean difference [MD] [weeks], -0.45; 95% CI, -0.64 to -0.25; P < .001; and OR, 1.55; 95% CI, 1.38 to 1.74; P < .001, respectively), regardless of whether the comparison group consisted of all unexposed mothers or only depressed mothers without antidepressant exposure. Antidepressant exposure during pregnancy was significantly associated with lower birth weight (MD [grams], -74; 95% CI, -117 to -31; P = .001); when this comparison group was limited to depressed mothers without antidepressant exposure, there was no longer a significant association. Antidepressant exposure was significantly associated with lower Apgar scores at 1 and 5 minutes, regardless of whether the comparison group was all mothers or only those who were depressed during pregnancy but not

Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

PubMed

Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

2014-05-01

Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

Drug–drug interactions involving antidepressants: focus on desvenlafaxine

PubMed Central

Low, Yvette; Setia, Sajita; Lima, Graca

2018-01-01

Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug–drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin–norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions. PMID:29497300

Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS

USGS Publications Warehouse

Schultz, M.M.; Furlong, E.T.

2008-01-01

Treated wastewater effluent is a potential environmental point source for antidepressant pharmaceuticals. A quantitative method was developed for the determination of trace levels of antidepressants in environmental aquatic matrixes using solid-phase extraction coupled with liquid chromatography- electrospray ionization tandem mass spectrometry. Recoveries of parent antidepressants from matrix spiking experiments for the individual antidepressants ranged from 72 to 118% at low concentrations (0.5 ng/L) and 70 to 118% at high concentrations (100 ng/L) for the solid-phase extraction method. Method detection limits for the individual antidepressant compounds ranged from 0.19 to 0.45 ng/L. The method was applied to wastewater effluent and samples collected from a wastewater-dominated stream. Venlafaxine was the predominant antidepressant observed in wastewater and river water samples. Individual antidepressant concentrations found in the wastewater effluent ranged from 3 (duloxetine) to 2190 ng/L (venlafaxine), whereas individual concentrations in the waste-dominated stream ranged from 0.72 (norfluoxetine) to 1310 ng/L (venlafaxine). ?? 2008 American Chemical Society.

The Rothschild Scale for Antidepressant Tachyphylaxis: reliability and validity.

PubMed

Rothschild, Anthony J

2008-01-01

After successful treatment of an episode of major depression, many patients complain of symptoms of apathy or decreased motivation (described by patients as "the blahs"), fatigue, dullness in cognitive function, sleep disturbance, weight gain, and sexual dysfunction; however, the characterization of this phenomenon of antidepressant tachyphylaxis has been hampered by the lack of an accepted definition and a reliable and valid assessment tool. To address this problem, the development and assessment of the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) are described. The RSAT consists of 6 self-report items assessing energy level, motivation and interest, cognitive functioning, weight gain, sleep, and sexual functioning. A seventh item, affect, is assessed by the interviewer. Each item is measured within a 5-point ordinal scale with anchor points developed to illustrate each rating. This study assesses the internal consistency, test-retest reliability, convergent and discriminant validity, sensitivity, specificity, and positive and negative predictive values of the RSAT. The RSAT demonstrated excellent internal consistency and scale reliability (Cronbach alpha = .902). The RSAT also demonstrated strong test-retest reliability (for depressed patients: r = 0.822, P < .01; for control subjects: r = 0.887, P < .01). The total RSAT score did not correlate with severity of depression as measured by the total Hamilton Depression Rating Scale score or the Hamilton Depression Rating Scale item 1 (depressed mood), supporting the discriminant validity of the RSAT for use in antidepressant tachyphylaxis. The RSAT is a reliable measure of antidepressant tachyphylaxis.

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

PubMed

Baune, Bernhard T; Brignone, Mélanie; Larsen, Klaus Groes

2018-02-01

Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. This study highlighted the large variability in measures used to assess cognitive functioning

Ionization pattern obtained in electrospray ionization or atmospheric pressure chemical ionization interfaces for authorized antidepressants in Romania

NASA Astrophysics Data System (ADS)

Grecu, Iulia; Ionicǎ, Mihai; Vlǎdescu, Marian; Truţǎ, Elena; Sultan, Carmen; Viscol, Oana; Horhotǎ, Luminiţa; Radu, Simona

2016-12-01

Antidepressants were found in 1950. In the 1990s there was a new generation of antidepressants. They act on the level of certain neurotransmitters extrasinpatic by its growth. After their mode of action antidepressants may be: SSRIs (Selective Serotonin Reuptake Inhibitors); (Serotonin-Norepinephrine Reuptake Inhibitors); SARIs (Serotonin Antagonist Reuptake Inhibitors); NRIs (Norepinephrine Reuptake Inhibitors); NDRIs (Norepinephrine-Dopamine Reuptake Inhibitors) NDRAs (Norepinephrine-Dopamine Releasing Agents); TCAs (Tricyclic Antidepressants); TeCAs (Tetracyclic Antidepressants); MAOIs (Monoamine Oxidase Inhibitors); agonist receptor 5-HT1A (5- hydroxytryptamine); antagonist receptor 5-HT2; SSREs (Selective Serotonin Reuptake Enhancers) and Sigma agonist receptor. To determine the presence of antidepressants in biological products, it has been used a system HPLC-MS (High Performance Liquid Chromatography - Mass Spectrometry) Varian 12001. The system is equipped with APCI (Atmospheric Pressure Chemical Ionization) or ESI (ElectroSpray Ionization) interface. To find antidepressants in unknown samples is necessary to recognize them after mass spectrum. Because the mass spectrum it is dependent on obtaining private parameters work of HPLC-MS system, and control interfaces, the mass spectra library was filled with the mass spectra of all approved antidepressants in Romania. The paper shows the mass spectra obtained in the HPLCMS system.

Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents.

PubMed

Sashidhara, Koneni V; Rao, K Bhaskara; Singh, Seema; Modukuri, Ram K; Aruna Teja, G; Chandasana, Hardik; Shukla, Shubha; Bhatta, Rabi S

2014-10-15

A series of amine substituted 3-phenyl coumarin derivatives were designed and synthesized as potential antidepressant agents. In preliminary screening, all compounds were evaluated in forced swimming test (FST), a model to screen antidepressant activity in rodents. Among the series, compounds 5c and 6a potentially decreased the immobility time by 73.4% and 79.7% at a low dose of 0.5 mg/kg as compared to standard drug fluoxetine (FXT) which reduced the immobility time by 74% at a dose of 20 mg/kg, ip. Additionally, these active compounds also exhibited significant efficacy in tail suspension test (TST) (another model to screen antidepressant compounds). Interestingly, rotarod and locomotor activity tests confirmed that these two compounds do not have any motor impairment effect and neurotoxicity in mice. Our studies demonstrate that the new 3-phenylcoumarin derivatives may serve as a promising antidepressant lead and hence pave the way for further investigation around this chemical space. Copyright © 2014 Elsevier Ltd. All rights reserved.

Potentially inappropriate medication: Association between the use of antidepressant drugs and the subsequent risk for dementia.

PubMed

Heser, Kathrin; Luck, Tobias; Röhr, Susanne; Wiese, Birgitt; Kaduszkiewicz, Hanna; Oey, Anke; Bickel, Horst; Mösch, Edelgard; Weyerer, Siegfried; Werle, Jochen; Brettschneider, Christian; König, Hans-Helmut; Fuchs, Angela; Pentzek, Michael; van den Bussche, Hendrik; Scherer, Martin; Maier, Wolfgang; Riedel-Heller, Steffi G; Wagner, Michael

2018-01-15

Potentially inappropriate medication (PIM) is associated with an increased risk for detrimental health outcomes in elderly patients. Some antidepressant drugs are considered as PIM, but previous research on the association between antidepressants and subsequent dementia has been inconclusive. Therefore, we investigated whether the intake of antidepressants, particularly of those considered as PIM according to the Priscus list, would predict incident dementia. We used data of a prospective cohort study of non-demented primary care patients (n = 3239, mean age = 79.62) to compute Cox proportional hazards models. The risk for subsequent dementia was estimated over eight follow-ups up to 12 years depending on antidepressant intake and covariates. The intake of antidepressants was associated with an increased risk for subsequent dementia (HR = 1.53, 95% CI: 1.16-2.02, p = .003; age-, sex-, education-adjusted). PIM antidepressants (HR = 1.49, 95% CI: 1.06-2.10, p = .021), but not other antidepressants (HR = 1.04, 95% CI: 0.66-1.66, p = .863), were associated with an increased risk for subsequent dementia (in age-, sex-, education-, and depressive symptoms adjusted models). Significant associations disappeared after global cognition at baseline was controlled for. Methodological limitations such as selection biases and self-reported drug assessments might have influenced the results. Only antidepressants considered as PIM were associated with an increased subsequent dementia risk. Anticholinergic effects might explain this relationship. The association disappeared after the statistical control for global cognition at baseline. Nonetheless, physicians should avoid the prescription of PIM antidepressants in elderly patients whenever possible. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting persistence to antidepressant treatment in administrative claims data: Considering the influence of refill delays and prior persistence on other medications

PubMed Central

Bushnell, Greta A; Stürmer, Til; White, Alice; Pate, Virginia; Swanson, Sonja A; Azrael, Deborah; Miller, Matthew

2016-01-01

Background Many patients with major depressive disorder (MDD) who begin antidepressant treatment discontinue use before for six months, the recommended minimum treatment length. This study sought to identify predictors of six-month antidepressant persistence including predictors utilizing patients’ electronic prescription records. Methods Commercially insured children (3–17 years) and adults (18–64 years) with MDD who initiated antidepressant treatment, 1/1/2003–2/28/2010, were assessed for six-month persistence (based on prescriptions’ days supply, allowing a 30-day grace period). Antidepressant persistence prediction models were developed separately for children and adults. Two additional measures, days without medication between the first and second antidepressant fill (children and adults) and prior persistence on other medications (adults only), were added to the models, concordance (c) statistics were compared and risk reclassification evaluated. Results Among children (n=8,837 children) and adults (n=47,495) with MDD, six-month antidepressant persistence was low and varied by age (37%, 18–24 years to 52%, 3–12 and 50–64 years, respectively). Independent baseline predictors of persistence were identified, with model c-statistics: children=0.582, adults=0.584. Patients with more days without medication between fills were less likely to be persistent (10–30 vs. 0 days, children: RR=0.72, adults: RR=0.74), as were adults not previously persistent to other medications (RR=0.73). Limitations The definition of 6-month persistence is dependent on correct days supply values and the grace period utilized; potential predictors were limited to measures available in claims data. Conclusions Six-month antidepressant persistence was low and overall prediction of persistence was poor; however, days without medication between fills and prior persistence on other medications marginally improved the ability to predict antidepressant persistence. PMID:26921866

Preclinical Evidence of Rapid-Onset Antidepressant-Like Effect in Radix Polygalae Extract

PubMed Central

Park, Hyunwoo; Kim, Yoorim; Park, Sung Hyun; Swanberg, Kelley; Shin, Joo-Yeon; Ha, Sang-Kyu; Cho, Yoonju; Bang, Soo-Yong; Lew, Jae-Hwan; Cho, Seung-Hun; Maeng, Sungho

2014-01-01

Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain

Identifying genetic loci affecting antidepressant drug response in depression using drug–gene interaction models

PubMed Central

Noordam, Raymond; Avery, Christy L; Visser, Loes E; Stricker, Bruno H

2016-01-01

Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., ‘treated-only design’, statistical power) and we will discuss how specifically drug–gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression. PMID:27248517

Genistein, a dietary soy isoflavone, exerts antidepressant-like effects in mice: Involvement of serotonergic system.

PubMed

Hu, Pei; Ma, Li; Wang, Yan-Gui; Ye, Feng; Wang, Chuang; Zhou, Wen-Hua; Zhao, Xin

2017-09-01

Genistein, a principal isoflavone property of soybeans, possesses multiple pharmacological activities such as neuroprotection. Recently, it was reported that genistein exerted antidepressant-like effects in animal models, but the mechanism of action remains ambiguous. The purpose of this study was to investigate the antidepressant-like effect of genistein in mice and explore the underlying mechanism(s), using two mouse models of depression, i.e. forced swim test (FST) and tail suspension test (TST). Chronic, but not acute (single dose), genistein treatment (5, 15 or 45 mg/kg, p.o., once per day for three weeks) exerted dose-dependently antidepressant-like effect in mice, concomitant with escalated levels of brain monoamines and suppressed monoamine oxidase (MAO) activity. Chemical depletion of brain serotonin by PCPA abrogated the antidepressant-like action of genistein, but it was not the case for ablation of NA by DSP-4. Moreover, the anti-depression by genistein was preferentially counteracted by co-administration of 5-HT 1A receptor antagonist WAY-100635, suggesting a pivotal role for 5-HT system coupled with 5-HT 1A receptors in mediating such genistein anti-depression. This point was further validated by the fact that genistein action was potentiated by co-treatment with 8-OH-DPAT, a selective 5-HT 1A receptor agonist. Collectively, these findings confirm that chronic genistein administration to mice engenders antidepressant-like efficacy evidenced by lessened behavioral despair. Serotonergic system that preferentially couples with 5-HT 1A receptors may be critically responsible for the present genistein anti-depression. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of purinergic and dopaminergic systems on MK-801-induced antidepressant effects in zebrafish.

PubMed

da Silva, Raquel Bohrer; Siebel, Anna Maria; Bonan, Carla Denise

2015-12-01

Depression is a serious disease characterized by low mood, anhedonia, loss of interest in daily activities, appetite and sleep disturbances, reduced concentration, and psychomotor agitation. There is a growing interest in NMDA antagonists as a promising target for the development of new antidepressants. Considering that purinergic and dopaminergic systems are involved in depression and anxiety states, we characterized the role of these signaling pathways on MK-801-induced antidepressant effects in zebrafish. Animals treated with MK-801 at the doses of 5, 10, 15, or 20μM during 15, 30, or 60min spent longer time in the top area of aquariums in comparison to control group, indicating an anxiolytic/antidepressant effect induced by this drug. Animals treated with MK-801 spent longer time period at top area until 2 (5μM MK-801) and 4 (20μM MK-801) hours after treatment, returning to basal levels from 24h to 7days after exposure. Repeated MK-801 treatment did not induce cumulative effects, since animals treated daily during 7days had the same behavioral response pattern observed since the first until the 7th day. In order to investigate the effects of adenosine A1 and A2A receptor antagonist and agonist and the influence of modulation of adenosine levels on MK-801 effects, we treated zebrafish with caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI during 30min before MK-801 exposure. The non-specific adenosine receptor antagonist caffeine (50mg/kg) and the selective A1 receptor antagonist DPCPX (15mg/kg) prevented the behavioral changes induced by MK-801. The non-specific nucleoside transporter (NT) inhibitor dipyridamole (10mg/kg) exacerbated the behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride and SCH 23390) did not change the behavioral alterations induced by MK-801. Our findings demonstrated that antidepressant-like effects of MK-801 in zebrafish are mediated through adenosine A1 receptor activation

Personality traits predict treatment outcome with an antidepressant in patients with functional gastrointestinal disorder.

PubMed

Tanum, L; Malt, U F

2000-09-01

We investigated the relationship between personality traits and response to treatment with the tetracyclic antidepressant mianserin or placebo in patients with functional gastrointestinal disorder (FGD) without psychopathology. Forty-eight patients completed the Buss-Durkee Hostility Inventory, Neuroticism Extroversion Openness -Personality Inventory (NEO-PI), and Eysenck Personality Questionnaire (EPQ), neuroticism + lie subscales, before they were consecutively allocated to a 7-week double-blind treatment study with mianserin or placebo. Treatment response to pain and target symptoms were recorded daily with the Visual Analogue Scale and Clinical Global Improvement Scale at every visit. A low level of neuroticism and little concealed aggressiveness predicted treatment outcome with the antidepressant drug mianserin in non-psychiatric patients with FGD. Inversely, moderate to high neuroticism and marked concealed aggressiveness predicted poor response to treatment. These findings were most prominent in women. Personality traits were better predictors of treatment outcome than serotonergic sensitivity assessed with the fenfluramine test. Assessment of the personality traits negativism, irritability, aggression, and neuroticism may predict response to drug treatment of FGD even when serotonergic sensitivity is controlled for. If confirmed in future studies, the findings point towards a more differential psychopharmacologic treatment of FGD.

Enhancing emotional-based target prediction

NASA Astrophysics Data System (ADS)

Gosnell, Michael; Woodley, Robert