Placebo Responses Among Men With Erectile Dysfunction Enrolled in Phosphodiesterase 5 Inhibitor Trials A Systematic Review and Meta-analysis

Question Was there an association between placebo and improved erectile function among men enrolled in studies of phosphodiesterase 5 inhibitors? Findings This systematic review and meta-analysis of 12 & x202f;564 men found a significant association between placebo and improved erectile function, with the effect size being larger among men with posttraumatic stress disorder. There was no difference between response to placebo and phosphodiesterase 5 inhibitors in men with erectile dysfunction after prostate surgery. Meaning The findings suggest that contextual factors are important in the delivery of care to patients with sexual dysfunction, and the lack of difference in response between placebo and phosphodiesterase 5 inhibitors in certain patient subgroups suggests that clinical practice should change. This systematic review and meta-analysis assesses whether there is an association between placebo and erectile dysfunction outcomes among men enrolled in placebo-controlled, phosphodiesterase 5 inhibitor trials. Importance Placebo responses in the treatment of erectile dysfunction (ED) are poorly described in the literature to date. Objective To quantify the association of placebo with ED outcomes among men enrolled in placebo-controlled, phosphodiesterase 5 inhibitor (PDE5I) trials. Data Sources For this systematic review and meta-analysis, a database search was conducted to identify double-blind, placebo-controlled studies using PDE5Is for the treatment of ED published from January 1, 1998, to December 31, 2018, within MEDLINE, Embase, Cochrane Library, and Web of Science. Only articles published in the English language were included. Study Selection Double-blind, placebo-controlled randomized clinical trials of PDE5Is for ED were included. Studies were excluded if they did not provide distribution measures for statistical analysis. Study selection review assessments were conducted by 2 independent investigators. A total of 2215 studies were identified from the database search, and after review, 63 studies that included 12 564 men were analyzed. Data Extraction and Synthesis Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Data were extracted from published reports by 2 independent reviewers. Quality assessment was performed using the Jadad scale. Data were pooled using a random-effects model. Main Outcomes and Measures The main outcome was improvement in the erectile function domain of the International Index of Erectile Function questionnaire in the placebo arm of the included studies. Effect size was reported as bias-corrected standardized mean difference (Hedges g). The hypothesis was formulated before data extraction. Results A total of 63 studies that included 12 564 men (mean [SD] age, 55 [7] years; age range, 36-68 years) were included. Erectile function was significantly improved among participants in the placebo arm, with a small to moderate effect size (Hedges g [SE], 0.35 [0.03]; P < .001). Placebo effect size was larger among participants with ED associated with posttraumatic stress disorder (Hedges g [SE], 0.78 [0.32]; P = .02) compared with the overall analysis. No significant difference was found between placebo and PDE5Is for ED after prostate surgery or radiotherapy (Hedges g [SE], 0.30 [0.17]; P = .08). Conclusions and Relevance In this study, placebo was associated with improvement of ED, especially among men with ED-related posttraumatic stress disorder. No difference was found between placebo and PDE5I among men treated for ED after prostate surgery.