BACKGROUND: Sexual dysfunction (SD) is prevalent in patients with major depressive disorder (MDD) and is also associated with second-generation antidepressants (SGAD) which are commonly used to treat the condition. Evidence indicates underreporting of SD in efficacy studies. SD associated with antidepressant treatment is a serious side effect that may lead to early termination of treatment and worsening of quality of life. OBJECTIVES: To systematically assess the harms of SD associated with SGAD in adult patients with MDD by drug type. METHODS: We retrieved English-language abstracts from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from reference lists of pertinent review articles and grey literature searches. Two independent reviewers identified randomized controlled trials (RCTs) of at least six weeks' duration and observational studies with at least 1,000 participants. STUDY SELECTION: Reviewers abstracted data on study design, conduct, participants, interventions, outcomes and method of SD ascertainment, and rated risk of bias. A senior reviewer checked and confirmed extracted data and risk of bias ratings. ANALYSES: Random effects network meta-analysis using Bayesian methods for data from head-to-head trials and placebo-controlled comparisons; descriptive analyses calculating weighted mean rates from individual trials and observational studies. RESULTS/ SYNTHESIS: Data from sixty-three studies of low and moderate risk of bias (58 RCTs, five observational studies) with more than 26,000 patients treated with SGAD were included. Based on network meta-analyses of 66 pairwise comparisons from 37 RCTs, most comparisons showed a similar risk of sexual dysfunction among included SGAD. Credible intervals, however, were wide and included differences that would be considered clinically relevant. We observed three main patterns: Bupropion had a statistically significantly lower risk of sexual dysfunction than some other SGAD, and both escitalopram, and paroxetine showed a statistically significantly higher risk of sexual dysfunction than some other SGAD. We found reporting of harms related to sexual dysfunction inconsistent and insufficient in some trials. LIMITATIONS: Most trials were conducted in highly selected populations. Search was restricted to English-language only. CONCLUSION AND IMPLICATIONS: Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of 2 outcome, we rated the overall strength of evidence with respect to our findings low. The current degree of evidence does not allow a precise estimate of comparative risk of sexual dysfunction associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients' preferences before initiating antidepressant therapy.

ObjectivesTo determine the effectiveness of interventions designed to prevent or reduce publication and related biases.Study Design and SettingWe searched multiple databases and performed manual searches using terms related to publication bias and known interventions against publication bias. We dually reviewed citations and assessed risk of bias. We synthesized results by intervention and outcomes measured and graded the quality of the evidence (QoE).ResultsWe located 38 eligible studies. The use of prospective trial registries (PTR) has increased since 2005 (seven studies, moderate QoE); however, positive outcome-reporting bias is prevalent (14 studies, low QoE), and information in nonmandatory fields is vague (10 studies, low QoE). Disclosure of financial conflict of interest (CoI) is inadequate (five studies, low QoE). Blinding peer reviewers may reduce geographical bias (two studies, very low QoE), and open-access publishing does not discriminate against authors from low-income countries (two studies, very low QoE).ConclusionThe use of PTR and CoI disclosures is increasing; however, the adequacy of their use requires improvement. The effect of open-access publication and blinding of peer reviewers on publication bias is unclear, as is the effect of other interventions such as electronic publication and authors' rights to publish their results.

Evidence on light therapy as preventive treatment for patients with a history of SAD is limited. Methodological limitations and the small sample size of the only available study have precluded review author conclusions on effects of light therapy for SAD. Given that comparative evidence for light therapy versus other preventive options is limited, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.

BackgroundWhen the nature and direction of research results affect their chances of publication, a distortion of the evidence base – termed publication bias – results. Despite considerable recent efforts to implement measures to reduce the non-publication of trials, publication bias is still a major problem in medical research. The objective of our study was to identify barriers to and facilitators of interventions to prevent or reduce publication bias.MethodsWe systematically reviewed the scholarly literature and extracted data from articles. Further, we performed semi-structured interviews with stakeholders. We performed an inductive thematic analysis to identify barriers to and facilitators of interventions to counter publication bias.ResultsThe systematic review identified 39 articles. Thirty-four of 89 invited interview partners agreed to be interviewed. We clustered interventions into four categories: prospective trial registration, incentives for reporting in peer-reviewed journals or research reports, public availability of individual patient-level data, and peer-review/editorial processes. Barriers we identified included economic and personal interests, lack of financial resources for a global comprehensive trial registry, and different legal systems. Facilitators identified included: raising awareness of the effects of publication bias, providing incentives to make data publically available, and implementing laws to enforce prospective registration and reporting of clinical trial results.ConclusionsPublication bias is a complex problem that reflects the complex system in which it occurs. The cooperation amongst stakeholders to increase public awareness of the problem, better tailoring of incentives to publish, and ultimately legislative regulations have the greatest potential for reducing publication bias.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-014-0551-z) contains supplementary material, which is available to authorized users.

SUMMARYIntroduction: To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus.