A Double Blind, Placebo Controlled, Randomized Trial to Evaluate the Efficacy and Tolerability of On-Demand Oral Pregabalin (150 mg and 75 mg) in Treatment of Premature Ejaculation
Mohamed Refaat El Najjar MD; Mohamed El Hariri MD; Ali Ramadan MD; Abd-Alrahman Hefny Hashem MBBCh
FIRST PUBLISHED: January 22, 2020 – The Journal of Sexual Medicine
Premature ejaculation (PE) is a common problem for men. The International Society for Sexual Medicine (ISSM) defines PE as follows:
a male sexual dysfunction characterized by
(i) ejaculation that always or nearly always occurs before or within approximately 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often of approximately 3 minutes or less (acquired PE);
(ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and
(iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy.
Past research has suggested that retarded ejaculation is a side effect of pregabalin, a gabapentinoid. The current study investigated whether pregabalin could be a potential PE treatment.
Materials and Methods
The study began with 120 male married participants between the ages of 18 and 50 with lifelong PE. Each had been married for at least four months and had sexual intercourse regularly with a female partner. The men were divided into three groups of 40 men each.
- Group A received 150 mg doses of pregabalin.
- Group B received 75 mg doses of pregabalin.
- Group C received a placebo.
Each patient was given 4 capsules of either pregabalin or placebo. Participants were advised to have sexual intercourse twice a week for two weeks, taking a capsule one to two hours before sexual activity. Intravaginal ejaculation latency time (IELT) – the amount of time between penetration and ejaculation – was measured by the man with a stopwatch. Men took note of any side effects that developed in the first 12 hours after taking the capsule.
Four baseline IELT measurements were taken before the study and averaged together for a baseline figure. The four measurements during the study period were also averaged together for comparison.
The study was completed by 116 participants.
Changes in IELT
The men in Group A (150 mg of pregabalin) had the greatest improvements in IELT.
||Mean Baseline IELT
||Mean Treatment IELT
|Group A (39 men)
||38.7 ± 15.2
||84.4 ± 50.7
|Group B (39 men)
||43.7 ± 12.7
||48.4 ± 20.3
|Group C (38 men)
||43.1 ± 13.4
||44.7 ± 14.8
On average, Group A’s IELT improvements were 2.45 ± 1.43-fold (145%) over baseline. Five patients achieved 2-minute IELTs, and two patients achieved 5-minute IELTs.
Thirty-two patients benefited from the treatment. Improvements did not appear to be related to patient age.
IELT improvements in Group B and Group C were “minimal and insignificant.”
Rates of adverse events were reported as follows:
Side effects were temporary and mild to moderate in severity. In participants taking pregabalin, dizziness and somnolence were the most commonly-reported adverse events.
“Taking the small number of cases and short duration into consideration, we cannot rely on this study to evaluate drug safety; however, pregabalin seems to be tolerable,” the authors wrote.
In terms of fold changes, pregabalin did not perform as well as other drugs used to treat PE, such as tramadol, dapoxetine, and clomipramine, which had fold improvements ranging from 4-fold to 13-fold in previous research. However, using higher doses of pregabalin and adjusting the timing could improve its results.
Pregabalin is safe in doses up to 600 mg a day, but more side effects may occur with higher doses. Taking pregabalin 1-2 hours before sexual activity was not considered “optimal timing.”
More research is necessary to determine the best dose and timing protocols for pregabalin.