What is the recommended dosing of Clomipramine (tricyclic antidepressant) for premature ejaculation?

From the Guidelines

Clomipramine is recommended for premature ejaculation at a dose of 25-50 mg taken 4-24 hours before sexual activity as needed, or a daily dosing regimen of 12.5-50 mg, with the goal of minimizing side effects and maximizing efficacy. The choice of dosing regimen, whether continuous daily dosing or situational dosing, often depends on the frequency of sexual activity by the patient 1. According to the most recent guideline, clinicians should recommend daily SSRIs, on-demand clomipramine or dapoxetine, and topical penile anesthetics as first-line agents of choice in the treatment of premature ejaculation 1.

Key Considerations

• The optimal interval for situational dosing before intercourse has not been established, but clomipramine can be taken 4-24 hours before sexual activity 1.
• The onset of action of clomipramine for premature ejaculation is unknown, but it may take 1-2 weeks of regular use to achieve optimal effects.
• Common side effects of clomipramine include drowsiness, dry mouth, constipation, and delayed ejaculation, which is the intended effect in this case.
• Clomipramine should be used cautiously in patients with cardiac conditions, seizure disorders, or those taking other serotonergic medications due to the risk of serotonin syndrome.

Dosing and Administration

• Start with the lowest effective dose to minimize side effects, and adjust as needed based on patient response.
• Clomipramine can be used as needed, or as part of a daily dosing regimen, depending on the patient's preferences and sexual activity level.
• Patients should be advised to avoid sudden cessation or rapid dose reduction of daily dosed clomipramine, as this may precipitate withdrawal symptoms 1.

Special Considerations

• Clomipramine is primarily approved for obsessive-compulsive disorder, but has shown effectiveness for premature ejaculation in multiple studies 1.
• Patients should be aware of the potential risks and benefits of using clomipramine for premature ejaculation, including the risk of serotonin syndrome and the potential for withdrawal symptoms if discontinued abruptly.

From the Research

Clomipramine Dosing for Premature Ejaculation

• The effective dose of clomipramine for premature ejaculation has been studied in several trials 2, 3, 4, 5.
• A study published in 1996 found that 25 mg of clomipramine taken as needed increased ejaculation latency in men with primary premature ejaculation from approximately 2 to 8 minutes 2.
• Another study published in 2001 found that daily treatment with 10-30 mg of clomipramine was effective in increasing ejaculatory latency in men with premature ejaculation who did not respond to 25 mg of clomipramine taken as needed 3.
• A systematic review and meta-analysis published in 2021 found that clomipramine significantly increased the intravaginal latency ejaculatory time (IELT) compared to placebo, and that higher doses of clomipramine resulted in a superior IELT without leading to higher risk of adverse events under a dosage of 50-mg clomipramine 5.

Dosage and Efficacy

• The optimal dosage of clomipramine for premature ejaculation remains controversial, but studies suggest that doses ranging from 25 mg to 50 mg may be effective 2, 3, 5.
• A study published in 1999 found that 25 mg of clomipramine taken 4 to 6 hours prior to sexual activity increased orgasmic latency in men with premature ejaculation from less than 1 minute to more than 3.5 minutes 4.
• The same study found that the beneficial effects of clomipramine were not uniform across clinical subjects, and that those with the shortest orgasmic latencies while on placebo were the least likely to substantially improve while on the drug 4.

Adverse Events

• Clomipramine has been associated with higher risks of overall adverse events and adverse events in the nervous and respiratory systems 6, 5.
• A systematic review and meta-analysis published in 2021 found that clomipramine was associated with higher risks of overall adverse events, but that the risk of adverse events did not increase significantly with higher doses of clomipramine under 50 mg 5.
• Another study published in 2001 found that daily treatment with 10-30 mg of clomipramine was well-tolerated, and that all four subjects expressed satisfaction with the treatment at follow-up 3.