Dapoxetine for the treatment of premature ejaculation: a meta-analysis of randomized controlled trials with trial sequential analysis

Abstract

Background: The safety and efficacy of dapoxetine for the treatment of premature ejaculation (PE) is still controversial. Thus, we decided to conduct a meta-analysis using trial sequential analysis (TSA) to determine the sufficiency of conclusions.

Objective: Evaluate the efficacy and safety of dapoxetine in the treatment of patients with PE and assess the reliability of the findings.

Design: Meta-analysis of randomized controlled trials (RCTs).

Methods: Electronic databases including PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang data were reviewed up to July 2017. RCTs evaluating the efficacy of dapoxetine in patients with PE and reporting intravaginal ejaculatory latency time (IELT), patient global impression of change (PGIC) and/or adverse events (AEs) were included.

Main outcome measures: Mean differences between trials in efficacy for IELT, and risk ratios for PGIC and treatment-emergent AEs.

Sample: 8 RCTs.

Results: For IELT and PGIC, significant effects were found for all doses of dapoxetine versus placebo, and similar results were obtained in subgroups of the 30-mg dose versus 60-mg dose. There were also statistically different dose-related effects on AEs. Trial sequential analysis showed that the result of our meta-analysis was confirmed and further trials are unnecessary.

Conclusions: The evidence suggests that dapoxetine may be a safe and effective drug for patients with PE.

Registration: Not registered, no published protocol.

Conflict of interest: No relationship with manufacturer of drug.

Figure 1

Flow diagram for selection of studies included in the meta-analysis.

Figure 2A

The summary of risk of bias by proportion of judgements.

Figure 2B

The summary of risk of bias by individual studies.

Figure 3A

Estimates for mean difference in IELT for dapoxetine (30 mg and 60 mg subgroup) and placebo group (favoring placebo means that IELT was 1.18 minutes shorter with placebo).

Figure 3B

Estimates for mean difference IELT for dapoxetine 30 mg group and 60 mg group after removal of outlier (the IELT was shorter with the 30 mg dose).

Figure 4

Trial sequential analysis for IELT for dapoxetine 30 mg versus placebo.The continuous blue line represents the Z curve, the continuous red horizontal lines represent the conventional boundary. The red non-horizontal lines represent the trial sequential monitoring boundary. The required information size was calculated as 33213. The Z curve has crossed the conventional boundary for harm and trial sequential monitoring boundary for harm, indicating the conclusion is sufficient and no more trials are needed.

Figure 5A

Trial sequential analysis for IELT for dapoxetine 30 mg versus dapoxetine 60 mg. The Z curve and boundaries are as in Figure 4. The required information size was calculated as 4114. The Z curve has crossed the conventional boundary for benefit and trial sequential monitoring boundary for benefit, indicating sufficient power to draw a definitive conclusion and no more trials are needed.

Figure 5B

Trial sequential analysis for IELT for dapoxetine 60 mg versus placebo. The Z curve and boundaries are as in Figure 4. The RIS was not renderable because the first information fraction exceeded 100% of the RIS. The Z curve has crossed the conventional boundary for harm and required information size, showing that the conclusion is sufficient and no more trials are needed.

Figure 5C

Trial sequential analysis for PGIC for dapoxetine 30 mg versus placebo. The Z curve and boundaries are as in Figure 4. The two red lines that intersect the horizontal coordinate line represent the futility boundary. The required information size was calculated as 2576. The Z curve has crossed the conventional boundary for harm and trial sequential monitoring boundary for harm, indicating sufficient power to draw a definitive conclusion and no more trials are needed.

Figure 5D

Trial sequential analysis for PGIC for dapoxetine 60 mg versus placebo. The Z curve and boundaries are as in Figure 4. The two red lines that intersect the horizontal coordinate line represent the futility boundary. The required information size was calculated as 3342. The Z curve has crossed the conventional boundary for harm and trial sequential monitoring boundary for harm, indicating sufficient power to draw a definitive conclusion and no more trials are needed.

Figure 5E

Trial sequential analysis for PGIC for dapoxetine 30 mg versus dapoxetine 60 mg. The Z curve and boundaries are as in Figure 4. The required information size was calculated as 1663. The Z curve has across the conventional boundary for benefit and trial sequential monitoring boundary for benefit, indicating sufficient power to draw a definitive conclusion and no more trials are needed.

Figure 5F

Trial sequential analysis for AEs for dapoxetine 30 mg versus placebo. The Z curve and boundaries are as in Figure 4. The required information size was calculated as 35923. The Z curve has crossed the conventional boundary for harm and trial sequential monitoring boundary for harm, indicating sufficient power to draw a definitive conclusion and no more trials are needed.

Figure 5G

Trial sequential analysis for AEs for dapoxetine 60 mg versus placebo. The Z curve and boundaries are as in Figure 4. The Z curve and boundaries are as in Figure 4. The required information size was calculated as 90530. The Z curve has crossed the conventional boundary for harm and trial sequential monitoring boundary for harm, indicating sufficient power to draw a definitive conclusion and no more trials are needed.

Figure 5H

Trial sequential analysis for AEs for dapoxetine 30 mg versus dapoxetine 60 mg. The Z curve and boundaries are as in Figure 4. The two red lines that intersect the horizontal coordinate line represent the futility boundary. The required information size was calculated as 5626. The Z curve has crossed the conventional boundary for benefit and trial sequential monitoring boundary for benefit, indicating sufficient power to draw a definitive conclusion and no more trials are needed.

Figure 6A

Estimates for risk ratio for PGIC for dapoxetine (30 mg and 60 mg subgroup) and placebo group (dapoxetine increased the PGIC by 1.98 times compared to placebo).

Figure 6B

Estimates for risk ratio for PGIC for dapoxetine 30 mg group and 60 mg group (dapoxetine 60 mg increased PGIC versus 30 mg).

Figure 7A

Estimates for the risk ratio for AEs for dapoxetine (30 mg and 60 mg subgroup) and placebo.

Figure 7B

Estimates for the risk ratio for AEs for dapoxetine 30 mg group and 60 mg group.