Pharmacologic interventions for antidepressant-induced sexual dysfunction: A systematic review and network meta-analysis of trials using the Arizona sexual experience scale

OBJECTIVE. Despite the prevalence of antidepressant-related sexual side effects, comparisons of treatments for these problematic side effects are lacking. METHODS. To address this, we performed a systematic review and Bayesian network meta-analysis to compare interventions for antidepressant-induced sexual dysfunction in adults. Using PubMed and clinicaltrials.gov, we identified prospective treatment studies for published and unpublished trials from 1985 through September 2020 (primary outcome: Arizona Sexual Experience [ASEX] Scale score). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS. We identified 57 citations (27 randomized controlled trials, 66 treatment arms, 27 open-label trials, 3 crossover trials) that evaluated 33 interventions (3108 patients). In the systematic review, 44% (25/57) of trials reported successful interventions; this was more common in open-label (70%, 19/27) compared to placebo-controlled studies (22%, 6/27). In the meta-analysis of placebo-controlled studies that used the ASEX (N=8), pycnogenol was superior to placebo (standardized mean difference: -1.8, 95% credible interval: [-3.7 to 0.0]) and sildenafil improved sexual dysfunction at a 6% threshold (standardized mean difference: -1.2, 95% credible interval [-2.5 to 0.1]). In the meta-analysis including single-arm studies (15 studies), treatment response was more common with sildenafil, tianeptine, maca, tiagabine, and mirtazapine compared to placebo, but these differences failed to reach statistical significance. CONCLUSIONS. While heterogeneity across randomized controlled trials complicates identifying the single best intervention, multiple trials suggest that sildenafil ameliorates antidepressant-induced sexual dysfunction. More RCTs are needed to examine the putative efficacy of other interventions.