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The article presents a paper on the effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) to treat children and adolescents with major depressive disorder (MDD) and anxiety disorders (AD). Based from the medical records, the number needed to treat (NNT) patients with AD acquired the percentage rating of 25%. Moreover, the author provides an overview on how the Canadian Academy Child and Adolescent Psychiatry (CACAP) has developed its information resources management to conduct several randomized clinical trials. A chart is presented depicting a comprehensive explanation on how the antidepressants works efficiently in the human bodies.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials, DB-RCTs) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over 6 months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

According to a systematic review on the use of selective serotonin reuptake inhibitors (SSRIs) in adult depression that was recently published in BMC Psychiatry, the results of which have been widely disseminated in lay media, these drugs increase the risk for serious adverse events (SAEs) while exerting poor antidepressant efficacy. A cursory analysis, however, suggests the analysis of SAEs conducted by the authors to be marred by both methodological inaccuracies and blatant errors. After having corrected for these apparent mistakes, we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age; while this suggests SSRIs to be safe drugs in the non-elderly, they do confirm what is already known, that is, that they may enhance the risk for SAEs in the old. Given the loose definition of SAE, including also innocuous phenomena, the possible clinical significance of the latter observation, however, remains unclear until the nature and actual impact of the SAEs in question have been clarified. Moreover, with respect to efficacy, we find the paper in BMC Psychiatry misleading: first , the authors seem unaware of the well-established shortcomings associated with the conventional efficacy parameter on which their analysis is based, second , they have included suboptimal SSRI doses and third , they have missed some pivotal trials. Unless there are explanations for the many peculiarities in this paper that have escaped us, and which may be satisfactorily clarified by the authors, it seems important that the conclusions presented in this paper be publicly rectified. [ABSTRACT FROM AUTHOR]

Before 1980, most people experiencing common nervous problems and who sought medical help complained of anxiety and were treated for anxiety. Similar experiences increasingly led to complaints of or treatment for panic attacks in the late 1980s and early 1990s, and to complaints of or treatment for mood disorders by the mid-1990s Today, such patient seem once again increasingly likely to complain of and be treated for anxiety. This paper reviews a series of mechanisms whereby company marketing can both transform the Perceptions of physicians and shape the experiences of those seeking treatment and the self-understanding of those not in treatment. These include the standard ploys of company sales departments to increase demand for products including celebrity endorsements the sponsoring of educational events and a host of reminders. The portfolio of marketing manoeuvres has grown, though, by translating educational events and celebrity events into the arena of scientific research: clinical trials have increasingly become part of the marketing of disorders and their treatments; ghost-written scientific papers are authored by celebrity researchers. The portfolio of marketing manoeuvres has also grown to encompass new ways of creating fashion through medical activism by setting up patient groups and disease awareness campaigns. The result is a transformation and growth in disorders tailor-made to fit ever more visible drugs. [ABSTRACT FROM AUTHOR]

Depression is the most prevalent mental disorder, affecting more than 300 million adults worldwide each year, which can lead to serious economic and social problems. Antidepressants are usually the first-line treatment for depression, however, traditional antidepressants on the market have the disadvantage of low remission rates and may cause side effects to patients, therefore, the current focus in the field of depression is to develop novel therapeutic agents with high remission rates and few side effects. In this context, the antidepressant effects of natural compounds have received attention. Baicalin (baicalein-7-O-glucuronide) and its aglycone baicalein (5,6,7-trihydroxyflavone) are flavonoid compounds extracted from the root of Scutellaria baicalensis. Although lacking the support of clinical data, they have been shown to have significantly promising antidepressant activity in many preclinical studies through various rodent models of depression. This paper reviews the antidepressant effects of baicalin and baicalein in experimental animal models, with emphasis on summarizing the molecular mechanisms of their antidepressant effects including regulation of the HPA axis, inhibition of inflammation and oxidative stress, reduction of neuronal apoptosis and promotion of neurogenesis, as well as amelioration of mitochondrial dysfunction. Controlled clinical trials should be conducted in the future to examine the effects of baicalin and baicalein on depression in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND: Public access to data has been a major step in attempting to reduce bias in scientific literature. Data to verify efficacy outcomes are now more accessible; however, little has been done to ensure public access to harms data from RCTs, which are equally important in ascertaining possible misreporting and protecting safety. OBJECTIVE: The treatment for adolescents with depression study (TADS) has influenced most international practice guidelines for treating children and adolescents with depression, supporting first-line prescription of fluoxetine in combination with cognitive behavioural therapy (CBT). However, after over 30 publications by the TADS team, reporting on harms remains highly deficient and we aimed to redress this lack. METHODS: In undertaking a restoring invisible and abandoned trials (RIAT) reanalysis of TADS' effectiveness and safety outcomes, we sought access to de-identified serious adverse events (SAE) data. RESULTS: This paper describes our unsuccessful efforts to obtain more detailed SAE data from TADS' data custodians, highlighting several problematic blocks to comprehensive safety reporting. CONCLUSION: Comprehensive access to clinical trial data is necessary to ensure safe and fully informed guidelines for treating children and adolescents with depression. [ABSTRACT FROM AUTHOR]

Background: Lower-sodium oxybate (LXB) is an oxybate medication with the same active moiety as sodium oxybate (SXB) and a unique composition of cations, resulting in 92% less sodium. LXB was shown to improve cataplexy and excessive daytime sleepiness in people with narcolepsy in a placebo-controlled, double-blind, randomized withdrawal study (NCT03030599). Additional analyses of data from this study were conducted to explore the effects of LXB on cataplexy, including the clinical course and feasibility of transition from other anticataplectics to LXB monotherapy. Objective: The aim of these analyses was to evaluate cataplexy frequency during initiation/optimization of LXB and taper/discontinuation of prior antidepressant/anticataplectic medications. Methods: Eligible participants (adults aged 18–70 years with narcolepsy with cataplexy) entered the study taking SXB only (group A), SXB + other anticataplectics (group B), or anticataplectic medication other than SXB (group C), or were cataplexy-treatment naive (group D). LXB was initiated/optimized during a 12-week, open-label, optimized treatment and titration period (OLOTTP). Other anticataplectics were tapered/discontinued during weeks 3–10 of OLOTTP. A 2-week stable-dose period (SDP; during which participants took a stable dose of open-label LXB) and 2-week double-blind randomized withdrawal period (during which participants were randomized to continue LXB treatment or switch to placebo) followed OLOTTP. Treatment-emergent adverse events (TEAEs) were recorded throughout the duration of the study. Results: At the beginning of OLOTTP, median weekly cataplexy attacks were lower in participants taking SXB at study entry (SXB only [2.00]; SXB + other anticataplectics [0.58]) versus participants who were taking other anticataplectics (3.50) or were anticataplectic naive (5.83). Median weekly cataplexy attacks decreased during weeks 1–2 of OLOTTP in all groups. Increased cataplexy frequency was observed in participants tapering/discontinuing other anticataplectics during weeks 3–10 and was more prominent in participants taking other anticataplectics alone compared with those taking SXB plus other anticataplectics. Cataplexy frequency decreased throughout initiation/optimization in anticataplectic-naive participants. Median number of cataplexy-free days/week at the end of SDP (study week 14) was similar in all groups (6.0, 6.1, 6.0, and 6.2 in groups A, B, C, and D, respectively). During OLOTTP and SDP, TEAEs of worsening cataplexy were reported in 0%, 47.8%, 16.7%, and 2.2% of participants in groups A, B, C, and D, respectively; most TEAEs of worsening cataplexy were reported during tapering/discontinuation of other anticataplectics. Conclusions: LXB monotherapy was effective in reducing cataplexy and increasing cataplexy-free days. These results illustrate the feasibility of switching from SXB to LXB while tapering/discontinuing other anticataplectics. Trial Registration: A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy; https://clinicaltrials.gov/ct2/show/NCT03030599; clinicaltrials.gov identifier: NCT03030599. Plain Language Summary: People with narcolepsy are often sleepy during the day. They may also have sudden muscle weakness (known as cataplexy). Lower-sodium oxybate (LXB) is a narcolepsy medicine that is similar to sodium oxybate (SXB) but has 92% less sodium. A recent study found that treatment with LXB was better at reducing how often people with narcolepsy had sleepiness and cataplexy than no medicine at all (NCT03030599). This paper is about the first 12 weeks of that study, when all the people taking part in the study first tried LXB to check that they were being given the right amount. In people who only took LXB, cataplexy happened less often over time. Some people were already taking other medicines to treat their cataplexy (such as antidepressants), so they were asked to slowly stop those medicines while taking LXB. In those people, cataplexy happened more often at first as they stopped taking antidepressants and then less often later on. The increase in cataplexy when antidepressants were stopped was smaller in people who switched from SXB to LXB. This study shows that many people getting treatment for narcolepsy can switch to LXB without their cataplexy becoming worse. [ABSTRACT FROM AUTHOR]

Selective reporting is prevalent in the medical literature, particularly in industry-sponsored research. In this paper, we expose selective reporting that is not evident without access to internal company documents. The published report of study 329 of paroxetine in adolescents sponsored by GlaxoSmithKline claims that “paroxetine is generally well tolerated and effective for major depression in adolescents”. By contrast, documents obtained during litigation reveal that study 329 was negative for efficacy on all 8 protocol specified outcomes and positive for harm. [ABSTRACT FROM AUTHOR]

Funded by the Danish state to provide guidance in health-related matters, the Copenhagen Trial Unit (CTU) at Rigshospitalet may cause considerable societal harm if allowing their analyses to be influenced by bias and prejudice rather than rigor and impartiality. This is why we found it worthwhile to comment on a report from the CTU in which the authors invoked analyses marred by numerous errors and methodological mistakes to claim that selective serotonin reuptake inhibitors (SSRIs) are harmful and ineffective. The CTU group has now produced a response to our comment which is on par with their original contribution in terms of bias, misconceptions and mistakes. Our conclusion is that the reputation of the CTU would be best served by the authors asking for retraction of their SSRI paper. [ABSTRACT FROM AUTHOR]

Background: The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety. Material and Methods: The PRISMA method was used in the literature search with the combination of the words 'bipolar,' 'manic,' 'mania,' 'manic depression,' and 'manic depressive' with 'randomized,' and 'algorithms' with 'mania,' 'manic,' 'bipolar,' 'manic-depressive,' or 'manic depression.' Relevant web pages and review articles were also reviewed. Results: The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice. Conclusions: A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses. [ABSTRACT FROM AUTHOR]

Precision medicine, in the sense of tailoring the choice of medical treatment to patients' pretreatment characteristics, is nowadays gaining a lot of attention. Preferably, this tailoring should be realized in an evidence-based way, with key evidence in this regard pertaining to subgroups of patients that respond differentially to treatment (i.e., to subgroups involved in treatment–subgroup interactions). Often a-priori hypotheses on subgroups involved in treatment–subgroup interactions are lacking or are incomplete at best. Therefore, methods are needed that can induce such subgroups from empirical data on treatment effectiveness in a post hoc manner. Recently, quite a few such methods have been developed. So far, however, there is little empirical experience in their usage. This may be problematic for medical statisticians and statistically minded medical researchers, as many (nontrivial) choices have to be made during the data-analytic process. The main purpose of this paper is to discuss the major concepts and considerations when using these methods. This discussion will be based on a systematic, conceptual, and technical analysis of the type of research questions at play, and of the type of data that the methods can handle along with the available software, and a review of available empirical evidence. We will illustrate all this with the analysis of a dataset comparing several anti-depressant treatments. [ABSTRACT FROM AUTHOR]

The Cochrane Library of Systematic Reviews is published quarterly. It now contains 2435 complete reviews. 1606 protocols of reviews and 5340 one page summaries of systematic reviews published in the general medical literature. In addition there are citations of 454.449 randomized controlled trials, 20 methodology reviews and 7059 cited papers in the Cochrane methodology register. The health technology assessment database contains 4620 citations. This edition of the Library contains 79 new reviews of which 6 have potential relevance for practitioners in pain and palliative medicine. [ABSTRACT FROM AUTHOR]

Background: Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation.Methods: PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: "duloxetine" OR "venlafaxine" OR "desvenlafaxine" OR "milnacipran" OR "levomilnacipran" OR "SNRI" OR "second generation antidepressant" OR "serotonin norepinephrine reuptake inhibitor" AND "discontinuation" OR "withdrawal" OR "rebound." Only published trials in the English language were included.Results: Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well.Conclusions: Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders. [ABSTRACT FROM AUTHOR]

Despite advances in clinical trial design, failure rates near 80% in phase 2 and 50% in phase 3 have recently been reported. The challenges to successful drug development are particularly acute in central nervous system trials such as for pain, schizophrenia, mania, and depression because high‐placebo response rates lessen assay sensitivity, diminish estimated treatment effect sizes, and thereby decrease statistical power. This paper addresses the importance of rigorous patient selection in major depressive disorder trials through an enhanced enrichment paradigm. This approach led to a redefinition of an ongoing, blinded phase 3 trial algorithm for patient inclusion (1) to eliminate further randomization of transient placebo responders and (2) to exclude previously randomized transient responders from the primary analysis of the double blind phase of the trial. It is illustrated for a case study for the comparison between brexpiprazole + antidepressant therapy and placebo + antidepressant therapy. Analysis of the primary endpoint showed that efficacy of brexpiprazole versus placebo could not be established statistically if the original algorithm for identification of placebo responders was used, but the enhanced enrichment approach did statistically demonstrate efficacy. Additionally, the enhanced enrichment approach identified a target population with a clinically meaningful treatment effect. Through its successful identification of a target population, the innovative enhanced enrichment approach enabled the demonstration of a positive treatment effect in a very challenging area of depression research. [ABSTRACT FROM AUTHOR]

Obesity is a significant clinical problem worldwide, posing an increasing challenge for both physicians and patients each year. Its complications affect physical and mental health, as well as social and economic consequences. The disease exhibits remarkable heterogeneity, leading to diverse pathogenesis among individuals. Despite a growing selection of weight -reducing medications and increased awareness of the importance of a healthy lifestyle, the effectiveness of obesity therapy often remains insufficient. This raises the question of whether tailoring obesity pharmacotherapy to specific phenotypes and individual patient characteristics results in improved treatment outcomes. Objective: To review literature on the effectiveness of obesity treatment based on the personalization of pharmacotherapy according to its underlying causes. Current Knowledge: Currently, the early outcome of weight loss is closely linked to the long-term effectiveness of obesity pharmacotherapy. However, due to the diversity of obesity pathogenesis, it is not helpful in selecting therapy at the initiation of treatment. Specific characteristics are sought to indicate the appropriate drug during therapy planning. In a U.S. study (Acosta et al., 2021), four obesity phenotypes were identified through relevant tests: "brain hunger," "intestinal hunger," "emotional hunger," and "slow burning." Subsequently, treatments were matched accordingly: phentermine with topiramate or lorcaserin, liraglutide, bupropion with naltrexone, and monotherapy with phentermine. The analysis results showed that phenotype-guided obesity pharmacotherapy resulted in clinically significant absolute weight loss of >10%, >15%, and >20% in 79%, 43%, and 30% of patients, respectively, after one year, compared to 35%, 17%, and 8% in the non-phenotyped group. Other studies demonstrated that for very rare types of obesity dependent on specific genetic mutations, targeted treatment addressing these defects yielded the best therapeutic outcomes (recombinant human leptin therapy for patients with leptin gene mutation - Farooqi et al., 2002; setmelanotide therapy for individuals with proopiomelanocortin deficiency - Clément et al., 2020). The impact of specific gene variants on therapeutic response should also be considered, leading to variability in treatment effects for different patients using the same drug. Conclusion: The concept of basing therapy on obesity phenotypes may currently serve as a guide for treatment selection, although it still requires confirmation in randomized clinical trials. Individualizing the choice of pharmacotherapy must primarily be based on the comprehensive patient picture: their preferences, contraindications, or coexisting conditions, with consideration of depression and the influence of antidepressant medications on body weight. [ABSTRACT FROM AUTHOR]

Introduction: Despite the development of many successful pharmaceutical interventions, a significant subset of patients experience treatment-resistant depression (TRD). Ketamine and its derivatives constitute a novel therapeutic approach to treat TRD; however, standard tools, such as the Montgomery– Åsberg Depression Rating Scale (MADRS) are still being used to measure symptoms and track changes. Methods: The aim of this study was to review item-level differences between rate of data change (MADRS score) and rater-weighted perception of the most useful items for assessing change in symptoms while remotely conducting the 10-item version of the MADRS in TRD in a clinical trial of rapid-acting antidepressants. Two studies of rapid-acting antidepressants in the treatment of TRD were used to identify itemscoring trends when MADRS is administered remotely and repeatedly (733 subjects across 10 visits). Scoring trends were evaluated in tandem to a rater survey completed by 75 raters. This was completed to gain insight on MADRS items’ perceived level of helpfulness when assessing change of symptoms in rapid-acting antidepressant trials. Results: MADRS items ‘Reduced sleep’, ‘Apparent sadness’, and ‘Pessimistic thoughts’ were found to have the greatest average data change by visit, while raters ranked ‘Reported sadness’, ‘Lassitude’ and ‘Apparent sadness’ as the most helpful items when assessing symptom change. Discussion: The diversion between rate of data-change ranking and rater perception of helpfulness could be related to difficulty in assessing specific items, to the novel treatment itself, and/or to the sensitivity to symptom change to which raters are accustomed in traditional antidepressant treatments. [ABSTRACT FROM AUTHOR]

Background: For many years, placebo has been defined by its inert content and use in clinical trials. In recent years, several studies have demonstrated its effect in the treatment of major depression. The aim of this paper is to present the conclusions of recent meta-analyses of the placebo effect in major depression, to explain the mechanism by which placebo exerts its effect, and to discuss whether placebo can be used in the treatment of patients with major depression in clinical practice. Recent meta-analyses have demonstrated that the placebo effect is estimated to account for 67% of the treatment effect in patients receiving antidepressants, and furthermore that placebo is as effective as antidepressants in patients with mild to moderate major depression (reporting a Hamilton Depression Rating Scale score lower than 25), whereas placebo is less effective than antidepressants in severely depressed patients. However, several limitations make the translation of these conclusions into clinical practice impracticable. Clinicians should learn from the "placebo lesson" to maximize the nonspecific effects of treatment when they prescribe an antidepressant, particularly in less severely depressed patients, who show a higher placebo response in randomized controlled trials. This strategy can increase the antidepressant effect and may reduce nonadherence with treatment [ABSTRACT FROM AUTHOR]

Although antidepressants continue to be a mainstay for clinicians who treat people suffering from depressive disorders, there have recently been articles published in both the scientific literature and the popular press that have raised questions about the utility of this class of medications. This paper briefly examines recent meta-analyses that have reported small drug versus placebo differences in randomized controlled trials and, from the perspective of a prescribing psychiatrist, discusses the clinical significance of these findings. It is concluded that antidepressants do have relatively modest effects (as compared with placebo) in contemporary randomized controlled trials, and that the contribution of placebo-expectancy factors to individual outcomes is often underestimated. Nevertheless, it is also concluded that the modest benefits of antidepressants in grouped datasets obscure large, specific, and very meaningful therapeutic effects for 10% to 20% of those treated with antidepressants. [ABSTRACT FROM AUTHOR]

AbstractBackground:This paper examines the current status of research on the efficacy and effectiveness of antidepressants. Methods:This paper reviews four meta-analyses of efficacy trials submitted to America’s Food and Drug Administration (FDA) and analyzes STAR*D (Sequenced Treatment Alternatives to Relieve Depression), the largest antidepressant effectiveness trial ever conducted. Results:Meta-analyses of FDA trials suggest that antidepressants are only marginally efficacious compared to placebos and document profound publication bias that inflates their apparent efficacy. These meta-analyses also document a second form of bias in which researchers fail to report the negative results for the pre-specified primary outcome measure submitted to the FDA, while highlighting in published studies positive results from a secondary or even a new measure as though it was their primary measure of interest. The STAR*D analysis found that the effectiveness of antidepressant therapies was probably even lower than the modest one reported by the study authors with an apparent progressively increasing dropout rate across each study phase. Conclusions:The reviewed findings argue for a reappraisal of the current recommended standard of care of depression.Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Copyright of Clinica y Salud is the property of Colegio Oficial de Psicologos de Madrid and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The objective of this paper is to evaluate the efficacy of nortriptyline for smoking cessation compared to placebo and bupropion sustained release.Randomized trials were identified by (1) checking electronic and (2) online publicly accessible registers of clinical trials; (3) searching references of identified studies and screening abstract books of conferences and symposia, and (4) personal communication with the first authors of identified papers.We included randomized trials in which nortriptyline was compared to placebo or bupropion hydrochloride SR. The main clinical outcome measure was (at least) 6-month prolonged abstinence, confirmed with a biochemical test. To investigate the efficacy of nortriptyline in time, we calculated the percentage of smokers who relapsed in time.We identified five randomized trials, including 861 smokers. Compared to placebo medication, nortriptyline resulted in significantly higher prolonged abstinence rates after at least 6 months[relative risk (RR) = 2.4, 95% CI 1.7–3.6; RD = 0.11, 95% CI 0.07–0.15]. The difference in efficacy between nortriptyline and placebo was highest in the first months after the target quit date. However, the number of people who remained abstinent decreased substantially and significantly faster over time in the nortriptyline group. Although bupropion resulted in higher abstinence rates compared with nortriptyline, the difference was not statistically significant (RR = 1.7, 95% CI 0.7–4.1).This systematic review and meta-analysis shows that the use of nortriptyline for smoking cessation resulted in higher prolonged abstinence rates after at least 6 months compared to placebo treatment. Furthermore, the use of nortriptyline for smoking cessation is well tolerated and safe. As a result, we believe health care professionals should be recommended to prescribe nortriptyline as a first-line therapy for smoking cessation, also because of the much lower cost of nortriptyline compared to bupropion SR. [ABSTRACT FROM AUTHOR]

Although practising evidence-based medicine is the goal of most physicians, it can be a real challenge to sift through the vast body of data to determine the best strategies. Most clinical guidelines regard replicated randomized controlled trials (RCTs), metaanalyses, and systematic reviews as the highest level of evidence to support treatment recommendations. High-quality metaanalyses can overcome many of the drawbacks of individual RCTs and qualitative reviews. They can reduce bias, provide adequate power to demonstrate real differences in outcomes, and resolve the results of inconsistent studies. This paper focuses on basic principles and terms used in metaanalysis, so that clinicians can appropriately evaluate and use their results to guide treatment decisions. [ABSTRACT FROM AUTHOR]

Depression in the elderly is a major public health problem as untreated depression adversely impacts comorbid illnesses. It is important to develop safe and effective antidepressant therapies for older individuals. We performed a systematic review of all published randomized, placebo-controlled antidepressant medication trials in populations over age 55 years. Papers were obtained via MEDLINE (1966-August 2003) and PSYCINFO (1872-August 2003). Unpublished trials, trials examining nonpharmacologic interventions, and papers reporting post hoc analyses were not included in this review unless they provided new insights. A total of I 8 placebo-controlled trials examining acute efficacy met our criteria. The combined sample size in these studies was 2252. The mean sample size was 51 (range 20-728) and mean trial duration was 7 weeks. A total of 12 trials examined tricyclic antidepressants (TCAs), five trials examined selective serotonin reuptake inhibitors (SSRIs), two trials examined bupropion, and one trial examined mirtazapine. There were no published trials of venlafaxine or nefazodone. In all, 71.5% of trials reported significantly greater efficacy with drug than placebo. In conclusions, there is a paucity of published controlled antidepressant trials in the elderly. Most published studies examine small sample sizes and do not include common comorbid conditions. Efficacy studies examining relapse prevention are lacking. Large placebo response rates, lack of controlled head to head comparisons, and other methodological design differences make crosstrial comparisons difficult Large simple studies are urgently needed to address the unmet needs for data on safety and efficacy of antidepressants in this population. [ABSTRACT FROM AUTHOR]

Tolerability and safety are important considerations in optimising pharmacotherapy for bipolar disorder. This paper reviews the tolerability and safety of lamotrigine, an anticonvulsant recommended in the 2002 American Psychiatric Association guidelines as a first-line treatment for acute depression in bipolar disorder and one of several options for maintenance therapy. This paper reviews the tolerability and safety of lamotrigine using data available from a large programme of eight placebo-controlled clinical trials of lamotrigine enrolling a total of nearly 1800 patients with bipolar disorder. This review is the first to collate all the safety information from these clinical trials, including data from four unpublished studies. The results these trials in which 827 patients with bipolar disorder were given lamotrigine as monotherapy or adjunctive therapy for up to 18 months for a total of 280 patient-years of exposure demonstrated that lamotrigine is well-tolerated with an adverse-event profile generally comparable with that of placebo. The most common adverse event with lamotrigine was headache. Lamotrigine did not appear to destabilise mood and was not associated with sexual adverse effects, weight gain, or withdrawal symptoms. Few patients experienced serious adverse events with lamotrigine, and the incidence of withdrawals because of adverse events was low. Serious rash occurred rarely (0.1% incidence) in the clinical development programme including both controlled and uncontrolled clinical trials. These findings - considered in the context of data showing lamotrigine to be effective for bipolar depression - establish lamotrigine as a well-tolerated addition to the psychotropic armamentarium. [ABSTRACT FROM AUTHOR]

The use of placebo in clinical trials has been repeatedly challenged as being unacceptable from an ethical point of view. The present paper responds to this criticism by taking up the issue in the light of the pertinent provisions of the Helsinki Declaration. Examples from different therapeutic areas are given that highlight the importance of placebo in situations in which its use is acceptable according to the Declaration. Particular emphasis is given to the question of active control trials, which, under conditions of low assay sensitivity, may become an ethically less acceptable approach than the use of a placebo control. [ABSTRACT FROM AUTHOR]

Background: Dysthymia is a prevalent form of subthreshold depressive disorder, associated with considerable disability and high co-morbidity. This paper systematically appraises the evidence for the efficacy and acceptability of the pharmacological treatment for this condition.Methods: Randomised, controlled trials evaluating the efficacy of drug therapies for dysthymia were included. A comprehensive search of the literature was performed, aiming to avoid publication bias. Pooled relative risks (RR) and 95% CIs were calculated with the Random Effect Model method. The number needed to treat (NNT) and number needed to harm (NNH) were estimated for statistically significant results.Results: Twenty-five trials were included for the main comparisons. Regarding placebo-controlled trials (n = 16), similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR for treatment response was 0.68 (95% CI 0.57-0.81) for TCA and the NNT was 4.3 (95% CI 3.2-6.5); 0.68 (95% CI 0.56-0.82) for SSRIs (NNT 5.1; 95% CI 3.9-7.7); 0.59 (95% CI 0.48-0.71) for MAOIs (NNT 2.9; 95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and ritanserin) showed similar results. The equivalent efficacy between antidepressants as found in trials where active medications were compared confirmed the efficacy findings from placebo trials. In general, patients treated with a TCA were more likely to report adverse events, compared with placebo and SSRIs.Conclusions: Pharmacotherapy for dysthymia appears to be an effective short-term treatment for dysthymic disorder. Newer antidepressants are equally effective and have better acceptability than TCAs, although their higher cost must be balanced against this assumed advantage. [ABSTRACT FROM AUTHOR]

Introduction: Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas covered: Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators. We also discuss other promising, non-glutamatergic targets for potential rapid antidepressant effects in mood disorders, including the cholinergic system, the glucocorticoid system, and the inflammation pathway, as well as several additional targets of interest. Clinical evidence is emphasized, and non-pharmacological somatic treatments are not reviewed. In general, this paper only explores agents available in the United States. Expert commentary: Of these novel targets, the most promising – and the ones for whom the most evidence exists – appear to be the ionotropic glutamate receptors. However, moving forward will require us to fully embrace the goal of personalized medicine and will require health professionals to pre-emptively identify potential responders. [ABSTRACT FROM AUTHOR]

Background: The current paper introduces the actual International College of Neuro-Psychopharmacology clinical guidelines for the treatment of bipolar disorder. Concept and structure of the guidelines: The current clinical guidelines are based on evidence-based data, but they also intend to be clinically useful, while a rigid algorithm was developed on the basis of firm evidence alone. Monotherapy was prioritized over combination therapy. There are separate recommendations for each of the major phases of bipolar disorder expressed as a 5-step algorithm. Discussion: The current International College of Neuro-Psychopharmacology clinical guidelines for the treatment of bipolar disorder are the most up-to-date guidance and are as evidence based as possible. They also include recommendations concerning the use of psychotherapeutic interventions, again on the basis of available evidence. This adherence of the workgroup to the evidence in a clinically oriented way helped to clarify the role of specific antidepressants and traditional agents like lithium, valproate, or carbamazepine. The additional focus on specific clinical characteristics, including predominant polarity, mixed features, and rapid cycling, is also a novel approach.Many issues need further studies, data are sparse and insufficient, and many questions remain unanswered. The most important and still unmet need is to merge all the guidelines that concern different phases of the illness into a single one and in this way consider BD as a single unified disorder, which is the real world fact. However, to date the research data do not permit such a unified approach. [ABSTRACT FROM AUTHOR]

This paper represents the position of the Canadian Psychiatric Association on the ethical and scientific issues related to the use of placebos in the evaluation of new psychotropic drugs. The position taken by the Association is that new psychotropic medications must be shown to he effective and must he weighed against the best current interventions. Placebo controls may be appropriate under certain circumstances, even when an established intervention is effective. These include situations in which placebo response rates are high, variable, or close to response rates for effective therapies. Placebo controls are also appropriate when established interventions carry a high risk of side effects or are effective against only certain symptoms of the disorder. [ABSTRACT FROM AUTHOR]

Through the history of rxisk.org, this article explores some of the Web's effects on the production and circulation of pharmaceutical knowledge. RxISK is an independent website that solicits reports from patients in order to uncover drug-induced harms which clinical trials and national pharmacovigilance schemes fail to identify. The first part of the article locates the origins of the project in the nearly 15-year struggle to obtain recognition and redress for one particular side effect of selective serotonin reuptake inhibitor (SSRI) antidepressants—their ability to trigger violent or suicidal behavior. That struggle, I show, brought to light the ways in which modern evidence-making practices obscure the harms of pharmacological treatment. The second part, based on interviews with the site's creators, examines how RxISK's data collection practices seek to convert the Web from a site for the circulation of misinformation into a usable source of new knowledge about drugs. The project's originality, I argue, lies in its effort to reframe the relation between anecdote and evidence so as to liberate the patient's voice from the burden of representativeness. Within this reframed epistemology, the project is also freed from the imperative of large-scale data extraction that increasingly dominates the economy of digital health. [ABSTRACT FROM AUTHOR]

The validity of mixed treatment comparisons (MTCs), also called network meta-analysis, relies on whether it is reasonable to accept the underlying assumptions on similarity, homogeneity, and consistency. The aim of this paper is to propose a practicable approach to addressing the underlying assumptions of MTCs. Using data from clinical studies of antidepressants included in a health technology assessment (HTA), we present a stepwise approach to dealing with challenges related to checking the above assumptions and to judging the robustness of the results of an MTC. At each step, studies that were dissimilar or contributed to substantial heterogeneity or inconsistency were excluded from the primary analysis. In a comparison of the MTC estimates from the consistent network with the MTC estimates from the homogeneous network including inconsistencies, few were affected by notable changes; that is, a change in effect size (factor 2), direction of effect or statistical significance. Considering the small proportion of studies excluded from the network due to inconsistency, as well as the number of notable changes, the MTC results were deemed sufficiently robust. In the absence of standard methods, our approach to checking assumptions in MTCs may inform other researchers in need of practical options, particularly in HTA. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the efficacy of Xiaoyaosan (XYS) for treatment of major depressive disorder (MDD) and to review the studies on antidepressant mechanisms of XYS. Methods: The China Knowledge Resource Integrated Database (1998-2014), VIP Journal Integration Platform (1989-2009), and PubMed (1950-2014) were used to search for and collect scientific publications related to XYS and MDD. Clinical trials for "MDD" and "xiaoyao" were screened. Papers that used the original prescription of XYS for treatment and in combination with Western medicines were included, while papers describing modified XYS were excluded. Four investigators read and screened the resulting publications independently, evaluated the associated scientific results and evidence. Results: There were no conclusive results to support the efficacy of XYS for treatment of MDD, owing to limited sample sizes, flaws in blinding and randomization, and lack of multi-centered clinical trials. Among the experimental studies on the effects of XYS possible involvement of 5-hydroxytryptamine, hypothalamic-pituitary-adrenal axis function, and neuroinflammation were possibly involved demonstrated. Conclusions: The effectiveness of XYS for treatment of MDD is uncertain. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments forMDDprimarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant inMDD.We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with theNIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants. [ABSTRACT FROM AUTHOR]

Although antidepressant drugs are commonly effective, several meta-analyses of antidepressant drug trials undertaken decades after their introduction suggested that they were effectively acting as placebos. A recent meta-analysis concluded that they were effective. Both conclusions have been widely taken up by the media. This paper seeks to explain the disconnect.Declaration of interestNone. [ABSTRACT FROM AUTHOR]

Levomilnacipran is a novel serotonin and norepinephrine reuptake inhibitor (SNRI) for the treatment of major depressive disorder. This paper reviews up-to-date data on the pharmacology, short- and long-term efficacy, safety and tolerability of levomilnacipran. The drug differs from previously available SNRIs in having twice the potency for norepinephrine versus serotonin reuptake inhibition. In four of the six short-term clinical trials, levomilnacipran was statistically significantly more efficacious than placebo. The only available relapse prevention study did not show reduction in time to relapse, perhaps because relapse rates were low. The commonest adverse events occurring twice as often as on placebo were nausea, hyperhidrosis, constipation, tachycardia, vomiting, erectile dysfunction, palpitations, and ejaculation disorder. In a few patients, hypertension or orthostatic hypotension may occur. Levomilnacipran has been shown to be effective in the short-term treatment of major depressive disorder and may represent an incremental advance. However, further research about its efficacy in subgroups of patients and comparing it to other antidepressants is needed. [ABSTRACT FROM AUTHOR]

Previous comparative reviews of add-on therapies for patients with major depressive disorder (MDD) with an inadequate response to antidepressants have not used meta-analytic techniques to compare different drug classes and have included non-licensed therapies. This meta-analysis reviewed all published peer-reviewed evidence for the efficacy of EU-licensed therapies in patients with MDD and an inadequate response to antidepressant monotherapy. Papers concerning randomized clinical trials (RCTs) were identified using criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Add-on therapies reviewed were antidepressants, quetiapine XR, lithium, and S-adenosyl-l-methionine (SAMe). Seven RCTs that reported response and remission in a way that allowed quantitative analysis were included in this meta-analysis. Comparison of the different drug classes indicated that most interventions had similar efficacy. The likelihood of response was significantly greater with SAMe versus placebo and lithium and with quetiapine XR versus placebo. Most add-on interventions demonstrated comparable efficacy in patients with MDD and an inadequate response to initial antidepressants. However, there is currently a paucity of high-quality data regarding the use of add-on treatments in patients with MDD who are inadequate responders to antidepressants, with quetiapine XR presenting the most comprehensive evidence base to date. [ABSTRACT FROM PUBLISHER]

Introduction: Systematic reviews of randomised placebo controlled trials of antidepressants have found small and decreasing differences in outcome between pharmacological and placebo arms. Increased knowledge of placebo characteristics may provide greater understanding of antidepressant pharmacological effect. We conducted a systematic review to identify the presence of key placebo characteristics in a sample of antidepressant clinical trials. Methods: 82 randomised placebo controlled trials of antidepressants, selected in 2 previous systematic reviews (Walsh et al. 2002; NICE 2009), were examined. Presence of placebo characteristics documented using detailed standardised form, with 5 domains: health care environment, practitioner characteristics, patient characteristics, practitioner-patient interaction, and non-pharmaceutical drug characteristics. First authors contacted where possible, and further clarification sought on placebo characteristics within trials. Results: Percentage of trials reporting placebo characteristics within the 5 domains: health care setting 100 %, environment 5 %; practitioner profession 18 %, status 0 %, incentives 0 %, gender 10 %, age 4 %, beliefs 6 %; patient age 85 %, gender 91 %, ethnicity 41 %, diagnosis and severity 100 %, recruitment 16 %, incentives 12 %, co-morbidity 12 %, expectation 0 %, beliefs 0 %; patient-practitioner interaction type of care 10 %, number of visits 94 %, empathy and congruence 2 %; drug form 45 % and frequency 57 %. Discussion: Placebo characteristics represent confounding variables which, if not adequately controlled for, could distort findings and conclusions about efficacy. The lack of systematic recording of many placebo characteristics in antidepressant drug trials is a cause for concern. To reduce imprecision and increase generalisability, future antidepressant clinical trials should consider the impact of key placebo characteristics and record their presence when disseminating findings. [ABSTRACT FROM AUTHOR]

This paper presents a systematic review of clinical trials of drugs for patients with personality disorders. Almost all trials have concerned the treatment of borderline personality disorder (BPD). Research yields some evidence for symptomatic improvement with antidepressants, mood stabilizers, and antipsychotics. However, drug treatment does not produce remission of BPD. Routine prescription of these agents for these patients is not evidence-based. [ABSTRACT FROM AUTHOR]

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We reply to the Ioannidis's paper "Effectiveness of antidepressants; an evidence based myth constructed from a thousand controlled trials." We disagree that antidepressants have no greater efficacy than placebo. We present the efficacy from hundreds of trials in terms of the percentage of patients with a substantial clinical response (a 50% improvement or more symptomatic reduction). This meta-analysis finds that 42-70% of depressed patients improve with drug and 21%-39% improve with placebo. The response benefit of antidepressant treatment is 33%-11% greater than placebo. Ioannidis argues that it would be vanishingly smaller because systematic biasing in these clinical trials would reduce the drug-placebo difference to zero. Ioannidis' argument that antidepressants have no benefit is eroded by his failures of logic because he does not present any evidence that there are a large number of studies where placebo is substantially more effective than drug. (To reduce to zero, one would also have to show that some of the unpublished studies find placebo better than drug and have substantial systematic or methodological bias). We also present the empirical evidence showing that these methodological concerns generally have the opposite effect of what Ioannidis argues, supporting our contention that the measured efficacy of antidepressants likely underestimates true efficacy. Our most important criticism is Ioannidis' basic underlying argument about antidepressants that if the existing evidence is imperfect and methods can be criticized, then this proves that antidepressant are not efficacious. He presents no credible evidence that antidepressants have zero effect size. Valid arguments can point out difficulties with the data but do not prove that a given drug had no efficacy. Indeed better evidence might prove it was more efficacious that originally found. We find no empirical or ethical reason why psychiatrists should not try to help depressed patients with drugs and/ or with psychotherapeutic/behavioral treatments given evidence of efficacy even though our treatment knowledge has limitations. The immense suffering of patients with major depression leads to ethical, moral, professional and legal obligations to treat patients with the best available tools at our disposal, while diligently and actively monitoring for adverse effects and actively revising treatment components as necessary. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a common, debilitating, chronic illness that emerges early in life and has serious consequences such as long-term unemployment and suicide. It confers considerable functional disability to the individual, their family and society as a whole and yet it is often undetected, misdiagnosed and treated poorly. In the past decade, many new treatment strategies have been trialled in the management of bipolar disorder with variable success. The emerging evidence, for pharmacological agents in particular, is promising but when considered alone does not directly translate to real-world clinical populations of bipolar disorder. Data from drug trials are largely based on findings that identify differences between groups determined in a time-limited manner, whereas clinical management concerns the treatment of individuals over the life-long course of the illness. Considering the findings in the context of the individual and their particular needs perhaps best bridges the gap between the evidence from research studies and their application in clinical practice. Specifically, only lithium and valproate have moderate or strong evidence for use across all three phases of bipolar disorder. Anticonvulsants, such as lamotrigine, have strong evidence in maintenance; whereas antipsychotics largely have strong evidence in acute mania, with the exception of quetiapine, which has strong evidence in bipolar depression. Maintenance data for anti- psychotics is emerging but at present remains weak. Combinations have strong evidence in acute phases of illness but maintenance data is urgently needed. Conventional antidepressants only have weak evidence in bipolar depression and do not have a role in maintenance therapy. Therefore, this paper summarizes the efficacy data for treating bipolar disorder and also applies clinical considerations to these data when formulating recommendations for the management of bipolar disorder. [ABSTRACT FROM AUTHOR]

Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy. Amisulpride has also been demonstrated to be an antidepressant for patients with major depression in many clinical trials. In part because of the selective D2/D3 receptor antagonist properties of amisulpride, it has long been widely assumed that dopaminergic modulation is the proximal event responsible for mediating its antidepressant and antipsychotic properties. The purpose of these studies was to determine if amisulpride’s antidepressant actions are mediated by off-target interactions with other receptors. We performed experiments that: (1) examined the pharmacological profile of amisulpride at a large number of central nervous system (CNS) molecular targets and, (2) after finding high potency antagonist affinity for human 5-HT7a serotonin receptors, characterized the actions of amisulpride as an antidepressant in wild-type and 5-HT7 receptor knockout mice. We discovered that amisulpride was a potent competitive antagonist at 5-HT7a receptors and that interactions with no other molecular target investigated in this paper could explain its antidepressant actions in vivo . Significantly, and in contrast to their wild-type littermates, 5-HT7 receptor knockout mice did not respond to amisulpride in two widely used rodent models of depression, the tail suspension test and the forced swim test. These results indicate that 5-HT7a receptor antagonism, and not D2/D3 receptor antagonism, likely underlies the antidepressant actions of amisulpride. [ABSTRACT FROM AUTHOR]

Over the past few years, a number of studies have suggested that the treatment of major depressive disorder (MDD) with anti-depressants enhancing both noradrenergic as well as serotonergic neurotransmission may result in higher response or remission rates than treatment with anti-depressants selectively enhancing serotonergic neurotransmission. The objective of this paper was to compare response rates among patients with MDD treated with either mirtazapine, an anti-depressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or selective serotonin reuptake inhibitors (SSRIs). Medline/Pubmed were searched. No year of publication limits were used. Double-blind, randomized clinical trials comparing mirtazapine with an SSRI for the treatment of MDD. Data were extracted with the use of a pre-coded form. Analyses were performed comparing response rates between the two anti-depressant agents. Data from 10 reports involving a total of 1904 outpatients with MDD were identified and combined using a random-effects model. Patients randomized to treatment with mirtazapine were as likely to experience clinical response as patients randomized to treatment with an SSRI (RR = 1.07; 95% CI: 0.96-1.2, P = 0.181). Simply pooling response rates between the two agents revealed a 67.1% response rate for mirtazapine and a 62.1% response rate for the SSRIs. There was no difference in overall discontinuation rates (RR = 1.1; 95% CI: 0.7-1.5; P = 0.550), discontinuation rates due to adverse events (RR = 0.9; 95% CI: 0.6-1.2; P = 0.497), or discontinuation rates due to lack of efficacy (RR = 0.9; 95% CI: 0.4-2.0; P = 0.871) between the two groups. Fewer mirtazapine-treated patients complained of insomnia (RR = 0.5; 95% CI: 0.3-0.9; P = 0.017), nausea (RR = 0.3; 95% CI: 0.3-0.5; P = 0.0001), whereas fewer SSRI-treated patients complained of fatigue (RR = 1.5; 95% CI: 1.1-2.4; P = 0.028), excessive sleepiness (RR = 1.3; 95% CI: 1.1-1.7; P = 0.020), weight-gain (RR = 3.8; 95% CI: 2.3-6.4; P = 0.0001) or dry mouth (RR = 1.8; 95% CI: 1.3-2.4; P = 0.0001) during the course of treatment. These results suggest that mirtazapine and the SSRIs differ with respect to their side-effect profile but not their overall efficacy in the treatment of MDD. [ABSTRACT FROM AUTHOR]