Despite the prevalence of antidepressant-related sexual side effects, comparisons of treatments for these problematic side effects are lacking.

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 Using PubMed and clinicaltrials.gov, we identified published and unpublished prospective treatment trials from 1985 to September 2020 (primary outcome: the Arizona sexual experience scale [ASEX] score).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.

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.

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.

Sexual dysfunctions are associated with multiple medical and psychiatric disorders, as well as pharmacotherapies used to treat these disorders. Although sexual dysfunctions negatively affect both quality of life and treatment adherence, patients infrequently volunteer these symptoms and clinicians do not pose directed questions to determine their presence or severity. This issue is especially important in psychiatric patients, for whom most common psychotropics may cause sexual dysfunctions (antidepressants, antipsychotics, anxiolytics and mood-stabilising agents). There is limited literature addressing benzodiazepines, and alprazolam in particular.

To report dose-dependent alprazolam anorgasmia.

Case analysis with PubMed literature review.

A 30-year-old male psychiatric patient presented with new-onset anorgasmia in the context of asymptomatic generalised anxiety disorder, social anxiety, panic disorder with agoraphobia, obsessive–compulsive disorder, major depression in remission, and attention-deficit hyperactivity disorder treated with escitalopram 10 mg q.a.m., gabapentin 1000 mg total daily dose, lisdexamfetamine dimesylate 70 mg q.a.m., nortriptyline 60 mg q.h.s. and alprazolam extended-release 2.5 mg total daily dose. All psychotropic doses had been constant for >6 months excluding alprazolam, which was titrated from 1 mg to 2.5 mg total daily dose. The patient denied any sexual dysfunction with alprazolam at 1 mg q.d. and 1 mg b.i.d. Within 1 week of increasing alprazolam to 2.5 mg total daily dose, the patient reported anorgasmia. Anorgasmia was alprazolam dose-dependent, as anorgasmia resolved with reduced weekend dosing (1 mg b.i.d. Saturday/1.5 mg total daily dose Sunday).

Sexual dysfunction is an important adverse effect negatively influencing therapeutic outcome. This case reports alprazolam-induced dose-dependent anorgasmia. Clinicians/patients should be aware of this adverse effect. Routine sexual histories are indicated.

None.