Clomipramine is a tricyclic antidepressant first developed in 1964 and still considered the most potent serotonin reuptake inhibitor available. People typically come to it for one of two reasons: severe obsessive-compulsive disorder that hasn't responded to SSRIs, or premature ejaculation, where even small doses can extend time to climax by several minutes.

It's not a first-line drug. Most psychiatrists reach for an SSRI first because clomipramine has a heavier side-effect load (dry mouth, sedation, weight gain, sexual dysfunction) and a real, dose-dependent seizure risk. But for the right person, especially someone with treatment-resistant OCD or lifelong PE, the trade-off can be worth it. Multiple meta-analyses still show it slightly outperforms SSRIs for OCD symptom reduction, even after correcting for trial bias.

Deep-dive

Dosage:

• For OCD: Start at 25 mg daily (10 mg if older or sensitive), preferably at bedtime to manage sedation. Titrate up by 25 mg every 4-7 days as tolerated. Most people land between 100-250 mg per day. The first 2 weeks should not exceed 100 mg
• For premature ejaculation (on-demand): 25 mg taken 3-6 hours before sex. Some respond to 15 mg. Going above 50 mg doesn't add benefit and just increases side effects
• For premature ejaculation (daily, if on-demand fails): 10-30 mg daily
• Splitting doses: During titration, split with meals to reduce nausea. Once stable, the full dose can be taken at bedtime
• Women: Consider starting at 10-25 mg and titrating more slowly. Plasma levels run higher at the same dose, so the same target may be reachable on less drug
• Older adults: Start at 10 mg, titrate slowly, and watch for dizziness on standing and confusion
• Hard ceiling: 250 mg per day in adults. Above this, seizure risk climbs sharply (about 0.5% at 250 mg, over 2% at 300+ mg)
• Stopping: Never stop abruptly. Taper by about 25% every 2-4 weeks. The cholinergic rebound can be severe (nausea, insomnia, sweating, anxiety)
• Time to effect: OCD response usually takes 6-12 weeks at full dose. PE effect is immediate when used on-demand

Here's what you can expect:

For OCD, expect a slow climb. The first few weeks are mostly about managing side effects while you titrate. Real symptom relief usually starts around week 4-6 and continues to deepen out to week 12. People typically describe it as the obsessive thoughts losing their grip, becoming easier to ignore rather than disappearing entirely. A 30-40% reduction in Y-BOCS score is considered a good response.

For premature ejaculation, the effect is almost mechanical. Most men taking 25 mg three to four hours before sex see latency extend from under a minute to several minutes, sometimes much longer. Some report a slight numbing or reduced sensation, which is typically the trade-off.

The first two weeks of any dose change tend to be the worst for side effects. Most settle as your body adapts.