Phosphodiesterase-5 inhibitors for premature ejaculation: a systematic review and meta-analysis

CONTEXT: Phosphodiesterase-5 inhibitors (PDE5is) are prescribed off-label for the treatment of premature ejaculation (PE). OBJECTIVE: To systematically review the evidence from randomised controlled trials (RCTs) for PDE5is in the management of PE. EVIDENCE ACQUISITION: MEDLINE and other databases were searched to September 2015. Quality of RCTs was assessed. Intra-vaginal ejaculatory latency time (IELT) data were pooled in a meta-analysis. Heterogeneity was assessed. EVIDENCE SYNTHESIS: Fifteen RCTs were included. The majority were of unclear methodological quality. Pooled IELT evidence suggests: PDE5is are significantly more effective than placebo (231 participants, p<0.00001); there is no difference between PDE5is and selective serotonin reuptake inhibitors (SSRIs) (405 participants, p=0.50); and that PDE5is combined with an SSRI are significantly more effective than SSRIs alone (521 participants, p=0.001). However, high levels of statistical heterogeneity are evident (I(2)≥40%). Single RCT evidence suggests that sildenafil is significantly more effective than the squeeze technique; but both lidocaine gel and tramadol are significantly more effective than sildenafil. Sildenafil combined with behavioural therapy is significantly more effective than behavioural therapy alone. Sexual satisfaction and ejaculatory control appear better with PDE5is compared with placebo and with PDE5is combined with an SSRI compared with an SSRI alone. Adverse events are reported with both PDE5is and other agents. CONCLUSIONS: PDE5is are significantly more effective than placebo and PDE5is combined with an SSRI are significantly more effective than SSRIs alone at increasing IELT and improvement in other effectiveness outcomes. However, heterogeneity is evident across RCTs. The methodological quality of the majority of RCTs is unclear. PATIENT SUMMARY: We reviewed PDE5is for treating premature ejaculation. We found evidence to suggest that PDE5is are effective compared with placebo and that PDE5is combined with an SSRI are better than an SSRI alone. Adverse events are reported with PDE5is and other agents. However, the quality of the evidence is uncertain. PROSPERO registration number: CRD42013005289.