Abstract: We included 23 trials involving 1886 people in this updated review. Twenty-two of these trials investigated the addition of medication to treat the identified dysfunction, with most agents studied in only single studies. One study investigated switching to an alternative antidepressant. In men, data for the phosphodiesterase inhibitors sildenafil (three studies, 255 participants) and tadalafil (one study, 54 participants) indicated they led to a greater improvement in erectile function than placebo. Combined data from three sildenafil studies found benefit over placebo on International Index of Erectile Function ratings of ability to achieve (MD 1.04, 95% CI 0.65 to 1.44), and maintain erections (MD 1.18, 95% CI 0.78 to 1.59). A single point improvement on these ratings is equivalent to an improvement in frequency from 'sometimes' to 'most times'. Men receiving tadalafil were more likely to report improved erectile function (RR 11.50, 95% CI 3.03 to 43.67). For women it remains uncertain whether sildenafil is more effective than placebo. Unpublished data could reduce this uncertainty. Data from three studies in men and women of bupropion 150 mg twice daily indicate a benefit over placebo on rating scale scores (SMD 1.60, 95% CI 1.40 to 1.81), but response rates in two studies of bupropion 150 mg once daily demonstrated no statistically significant difference in effect (RR 0.62, 95% CI 0.09 to 4.41). Other augmentation strategies failed to demonstrate significant improvements in sexual dysfunction compared with placebo. One trial involving 75 people with sexual dysfunction due to sertraline assessed the effect of changing antidepressant. Switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction than restarting sertraline (RR 0.34, 95% CI 0.19 to 0.60), however, nefazodone is no longer available for clinical use. There is an absence of randomised trials assessing the effects of switching to currently-available antidepressant agents with lower rates of adverse sexual effects, the role of psychological or mechanical interventions, or of techniques such as drug holidays. We identified no data for any of the strategies included in the trials assessed that indicated that they led to a worsening of psychiatric symptoms. However, the relatively small numbers assessed for many of the interventions studied means that the possibility of such an effect cannot confidently be excluded in all cases. Given the small numbers of studies assessing most of the strategies assessed, the presence of any unpublished trials could have substantial effects on estimates of effect. In some cases, only results from particular items or subscales within ratings scales are available. It is likely that this could act to bias estimates of effect obtained, increasing apparent effectiveness. The evidence currently available is rather limited. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil or tadalafil appears to be an effective strategy. For women with antidepressant-induced sexual dysfunction the addition of bupropion at higher doses appears to be the most promising approach studied so far.

Plain-language summary: This systematic review investigated different ways to manage such sexual dysfunction. We included 23 randomised studies, with a total of 1886 participants who had developed their sexual problems while taking antidepressant medication. Twenty-two of these studies looked at the addition of further medication to the ongoing treatment for depression. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil (Viagra; three studies, 255 participants) or tadalafil (Cialis; one study, 54 participants) appeared to improve the situation. For women with antidepressant-induced sexual dysfunction the addition of bupropion (Wellbutrin, Zyban; three studies, 482 participants) at higher doses appears to be the most promising approach studied so far, but further data from randomised trials are likely to be required before it can be recommended confidently. We did not find evidence that any intervention led to a worsening of psychiatric symptoms; however, we cannot be confident of this for many of the interventions studied, as only small numbers of participants have been studied so far.