Clomipramine (Anafranil)

What it treats

Clomipramine is approved by the U.S. Food and Drug Administration to treat obsessive-compulsive disorder in adults and children age 10 and older.

Off-label uses include depression, panic disorder, and some chronic pain conditions. Off-label means a purpose the label doesn't formally list even though evidence and practice support it.

How it works

Clomipramine acts on serotonin and, to a lesser extent, norepinephrine, two of the brain's chemical messengers. It also blocks histamine and acetylcholine, which is why sedation, dry mouth, and constipation are common.

For OCD, the benefit is thought to come from strong, sustained serotonin activity. As with other antidepressants, the effect isn't from the first dose. It comes from slower changes in the brain over weeks, and OCD often needs longer trials (10 to 12 weeks at a full dose) than depression.

Receptor mechanism (detail)

Clomipramine is a tertiary-amine tricyclic and the most serotonin-selective of the tricyclics (SERT greater than NET). Its main metabolite, desmethylclomipramine, is a strong NET inhibitor, which is part of why the drug has a dual profile in practice. It also blocks muscarinic (M1), histamine (H1), and alpha-1 receptors, driving dry mouth, sedation, constipation, and orthostatic hypotension. Seizure threshold is lowered, more so at doses above 250 mg per day.

Potency and typical dosing pattern

Ranges are typical framework only, not a prescription for any individual.

Starting is 25 mg per day. Titration goes up over about two weeks to 100 mg per day, then further as tolerated to a maximum of 250 mg per day for adults. In children and adolescents, the maximum is lower (about 3 mg/kg or 200 mg per day, whichever is smaller). Full response for OCD often takes 10 to 12 weeks.

Safety monitoring

• ECG at baseline, and periodically at higher doses. Tricyclics prolong QRS, PR, and QTc.
• Overdose is dangerous. Narrow therapeutic index; even modest overdoses can cause fatal arrhythmias.
• Seizure risk rises at higher doses (especially above 250 mg per day).
• Anticholinergic burden.
• Orthostatic vitals.
• Suicidality in the first 4 weeks, especially under age 25 (FDA boxed warning).
• Serotonin syndrome, avoid MAOIs and combinations with strongly serotonergic drugs.
• Reassess at 4, 8, and 12 weeks for OCD; sooner if depression is the target.

What to expect

Common side effects

Common side effects include:

• Dry mouth.
• Constipation.
• Drowsiness.
• Blurred vision.
• Weight gain.
• Dizziness on standing.
• Sweating.
• Tremor.
• Sexual side effects (particularly delayed orgasm, which is very common).

If a side effect is severe, or it isn't improving, that's a conversation to have with the prescriber rather than a reason to stop on your own.

Serious side effects and warnings

Serious problems are uncommon, but a few are worth knowing.

Boxed warning. Like all antidepressants, clomipramine carries an FDA boxed warning that it can increase suicidal thoughts and behaviors in children, teenagers, and young adults under 25, especially in the first weeks of treatment or after a dose change.

• Seizures. Clomipramine lowers the seizure threshold more than most tricyclics. Risk climbs above 250 mg per day and with other seizure-lowering drugs.
• Effects on heart rhythm. ECG monitoring matters.
• Danger in overdose. Fatal arrhythmias are possible.
• Serotonin syndrome. Do not combine with MAOIs; caution with tramadol, triptans, linezolid, other serotonergic drugs.
• Anticholinergic burden, meaningful in older adults; Beers Criteria caution.
• A drop in blood pressure on standing.

Sexual side effects

Sexual side effects are prominent with clomipramine. Delayed orgasm is very common. Reduced desire and erectile difficulty also occur. These are worth naming up front because they're a leading reason for discontinuation. There are options if they become intolerable, including dose reduction, augmentation strategies, or switching.

Weight, appetite, and sleep

Clomipramine commonly increases appetite and causes weight gain. It's sedating for most people, which is why it's often taken at bedtime.

Starting and dosing basics

This section is general background, not a dosing instruction for any individual. The right dose is a decision for a prescriber.

Clomipramine comes as capsules. Starting at a low dose reduces the early nausea and sedation. Doses are usually taken in the evening or split. Full trials for OCD need 10 to 12 weeks at a dose that has been pushed to the tolerated maximum, which is often 150 to 250 mg per day.

Missed doses and interactions

If you miss a dose, take it when you remember, unless it's almost time for the next dose. Skip the missed dose and carry on. Don't take two doses to make up for one.

Interactions matter. Clomipramine must not be combined with MAOI antidepressants, and a gap is needed when switching. CYP inhibitors (fluoxetine, paroxetine, fluvoxamine, bupropion) can raise levels sharply. Alcohol and other CNS depressants add to sedation. Other serotonergic drugs raise serotonin syndrome risk. Give every prescriber and pharmacist a full list of your medications and supplements, including over-the-counter ones.

Stopping and tapering

Clomipramine isn't a controlled substance and isn't habit-forming in the usual sense.

The body does adjust to it, and stopping abruptly can cause discontinuation symptoms: nausea, sweating, cholinergic rebound, insomnia, and a return of OCD symptoms. A gradual taper planned with a prescriber avoids most of this.

Pregnancy and breastfeeding

This is an area where individual circumstances matter and the decision belongs with a clinician. Untreated OCD and depression carry their own risks during pregnancy, and clomipramine passes into breast milk. Anyone who is pregnant, planning a pregnancy, or breastfeeding should talk it through with their prescriber so the specific risks and benefits can be weighed for their situation.

Cost and generic availability

Clomipramine has been available as a generic for many years and is inexpensive. Generic clomipramine contains the same active medication as the brand name Anafranil and works the same way. Most insurance plans cover it.

Common questions

Why is clomipramine used for OCD when there are SSRIs? For OCD, clomipramine has some of the strongest efficacy data of any single medication. SSRIs come first because they're gentler, but clomipramine remains a real option when SSRIs haven't been enough.

How long does it take to work for OCD? Longer than for depression. Full response often takes 10 to 12 weeks at a dose that has been pushed as high as the person can tolerate.

Why is seizure risk mentioned so often? Clomipramine lowers seizure threshold more than most tricyclics, especially above 250 mg per day. That's why the maximum dose is capped and why other seizure-lowering drugs need caution.

Will it affect sex? Very likely. Delayed orgasm is one of its most common side effects. Talking about this early makes it easier to plan.

Is it addictive? No. It's not a controlled substance and doesn't cause cravings. Stopping should still be done gradually.

Questions to ask your prescriber

• We're treating OCD (or another condition). What does full response look like?
• Which side effects should I expect, and which should I call about?
• Is 10 to 12 weeks a reasonable time frame before we judge response?
• If sexual side effects are a problem, what are our options?
• If we decide to stop it later, how would we do that safely?

Sources

This guide draws on current prescribing information and public health references and current as of June 8, 2026. It is reviewed for clinical accuracy and updated as guidance changes.

• U.S. Food and Drug Administration. Clomipramine hydrochloride (Anafranil) prescribing information.
• MedlinePlus, U.S. National Library of Medicine. Clomipramine.
• National Institute of Mental Health. Mental health medications.
• American Psychiatric Association. Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder.
• National Institute for Health and Care Excellence (NICE). CG31, Obsessive-compulsive disorder and body dysmorphic disorder.