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

Marissa J Luft; Eric T Dobson; Amir Levine; Paul E Croarkin; Jeffrey R Strawn

doi:10.1017/S1092852921000377

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

CNS Spectr. 2021 Apr 12:1-10. doi: 10.1017/S1092852921000377. Online ahead of print.

Authors

Marissa J Luft¹, Eric T Dobson², Amir Levine³, Paul E Croarkin⁴, Jeffrey R Strawn¹

Affiliations

¹ Anxiety Disorders Research Program, Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, USA.
² Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
³ Department of Psychiatry, Columbia University and New York State Psychiatric Institute (NYSPI), New York, New York, USA.
⁴ Mayo Clinic, Department of Psychiatry and Psychology, Rochester, Minnesota, USA.

PMID: 33843553
DOI: 10.1017/S1092852921000377

Abstract

Background: 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 Using PubMed and clinicaltrials.gov, we identified published and unpublished prospective treatment trials from 1985 to September 2020 (primary outcome: the Arizona sexual experience scale [ASEX] score). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Results: We identified 57 citations (27 randomized controlled trials, 66 treatment arms, 27 open-label trials, and 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 [CrI]: [-3.7 to 0.0]) and there was evidence that, at a 6% threshold, sildenafil improved sexual dysfunction (standardized mean difference: -1.2, 95% CrI [-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 randomized controlled trials are needed to examine the putative efficacy of other interventions.

Keywords: Selective serotonin reuptake inhibitor (SSRI); anorgasmia; erectile dysfunction; sexual dysfunction; sildenafil.