Efficacy and Safety of Phosphodiesterase-5 Inhibitors for Erectile Dysfunction in Schizophrenia: A Systematic Review and Meta-Analysis

Background: The benefits of phosphodiesterase-5 inhibitors in the treatment of sexual dysfunction and psychopathology of schizophrenia remain unclear. This systematic review and meta-analysis aimed to address the above clinical question. Methods: Our primary outcome includes erectile dysfunction (ED) assessed using standardized questionnaires. Other efficacy outcomes involve overall sexual dysfunction, overall schizophrenia symptoms, positive symptoms, and negative symptoms. Further, we included all-cause discontinuation, discontinuation due to adverse events, discontinuation due to consent withdrawal, headache, loss of appetite, and somnolence. A meta-analysis was conducted for outcomes if at least two studies in each drug group had sufficient data to conduct a meta-analysis for a specific outcome. Results: Our systematic review included five double-blind, randomized, placebo-controlled trials (n=155, mean age=37.18 years, male proportion=91.61%), consisting of one lodenafil, three sildenafil, and one tadalafil study. Among the three studies on sildenafil, only one reported outcomes on sexual dysfunction; however, it demonstrated that sildenafil improved ED in males with schizophrenia. Another study reported that sildenafil also outperformed placebo in terms of schizophrenia symptom improvement, especially negative symptoms. However, our meta-analysis revealed no significant differences in outcomes associated with psychopathology, all-cause discontinuation, discontinuation due to adverse events, discontinuation due to consent withdrawal, headache, loss of appetite, and somnolence between sildenafil and placebo. Tadalafil outperformed placebo in terms of ED improvement although this finding was derived from one study. Conclusion: Sildenafil and tadalafil may be treatment options for ED, although our meta-analysis of safety outcomes did not include tadalafil. Our meta-analysis revealed that sildenafil was well accepted and well tolerated, despite involving only two studies.