Sexual Dysfunction associated with Second-Generation Antidepressants in Patients with Major Depressive Disorder: Results from a Systematic Review with Network Meta-Analysis

Abstract

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.

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A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy

“…If an antidepressant is prescribed, then clinicians should discuss potential adverse sexual side effects and drug-drug interactions [Dauchy et al 2013]. There is evidence that some psychotropic medications, such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants, are associated with decreased libido [Reichenpfader et al 2014], delayed orgasm [Montejo et al 2001], continence and flow dysfunction [Pollack et al 1992]. Furthermore, antidepressants that are strong CYP2D6 (cytochrome P450 2D6) inhibitors may decrease the efficacy of TAM and are relatively contraindicated [Sideras et al 2010].…”

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“…1 Whereas 26% of nondepressed people report some sexual dysfunction, this number increases to 45% in people with untreated depression, and to 63% in medically treated patients with depression. 2 In addition to high levels of baseline SD in patients with depression, many antidepressant medications independently cause SD in any or all phases of the sexual response cycle, including libido, arousal, orgasm, and ejaculation.…”

“…2 In addition to high levels of baseline SD in patients with depression, many antidepressant medications independently cause SD in any or all phases of the sexual response cycle, including libido, arousal, orgasm, and ejaculation. 1 …”