Clomipramine-sildenafil combo tied to better outcomes in men with PE

The combination regimen of clomipramine and sildenafil led to better outcomes than clomipramine or sildenafil alone in men with premature ejaculation (PE) without erectile dysfunction (ED), according to a study presented at EAU25.

The researchers conducted a prospective, double-blinded, active-controlled trial involving 795 men with PE but no ED, who were recruited from 24 institutions in Korea. The participants were randomized to receive clomipramine 15 mg (group A: n=265), sildenafil 50 mg (group B: n=266), or a combination regimen of clomipramine 15 mg and sildenafil 50 mg (group C: n=264). Stopwatch-measured IELT* and patient-reported outcomes using PEP** and PGIC*** questionnaires were assessed during the 12-week treatment period.

At visit 5 (8–12 weeks post-dose), mean IELTs significantly increased by 191.72 secs (p<0.001) in group A, 168.35 secs (p<0.001) in group B, and 279.41 secs (p<0.001) in group C.

Notably, individuals who received clomipramine plus sildenafil had a significant improvement in mean IELT from baseline than those who were on clomipramine (mean 272.61 vs 191.61 secs; p=0.0007) or sildenafil alone (mean 272.61 vs 162.47 secs; p<0.0001). [EAU25, abstract A0559]

In terms of PEP scores, a significantly higher proportion of patients treated with the combination regimen achieved an improvement in each item score of the PEP at visit 5 compared with those on clomipramine only (96.10 percent vs 91.46 percent; p=0.0474) or sildenafil alone (96.10 percent vs 85.59 percent; p=0.0001).

Significantly more patients receiving clomipramine plus sildenafil also achieved an increased score in “perceived control over ejaculation” and a decreased score in “personal distress” than those receiving clomipramine or sildenafil alone (50.08 percent vs 40.89 percent; p=0.0368 and 29.37 percent; p<0.0001, respectively).

Similarly, the PGIC score was significantly improved in group C than in group A or B, with more clomipramine plus sildenafil recipients reporting “much better” than the clomipramine- (p=0.0046) and sildenafil-alone (p=0.0001) recipients.

Adverse events

Although the combination group (25 percent) experienced a higher rate of treatment-emergent adverse events (TEAEs) than the clomipramine- (17.36 percent) or sildenafil-alone (16.17 percent) groups, this did not reach statistically significant differences between the treatment groups.

Headache (9.09 percent), nausea (7.58 percent), flushing (7.95 percent), and dizziness (3.41 percent) were the most common TEAEs reported in the combination group. These TEAEs were mostly mild to moderate in severity, with no serious TEAEs reported.

“Overall, on-demand therapy with clomipramine and sildenafil combination showed better results in terms of IELT, PEP, and PGIC, and was similar in safety, compared with clomipramine or sildenafil alone,” said lead author Dr Du Geon Moon from Korea University Guro Hospital in Seoul, South Korea.

These findings suggest that the use of clomipramine and sildenafil combination may have a potential role in treating patients with PE who have no history of ED, he added.