How should I taper off Clomipramine (clomipramine)?

Most serotonergic of the TCAs; withdrawal often resembles SSRI discontinuation in addition to anticholinergic rebound. Capsules can be opened for bead counting where finer increments are needed. Strong SERT inhibition produces SSRI-like withdrawal in addition to cholinergic rebound. Apply slow hyperbolic reductions (~10% per step) over months; bead counting from capsules supports sub-strength dosing.

Clomipramine Tapering Guide

Q: What are the withdrawal symptoms of Clomipramine (clomipramine)?

Common withdrawal symptoms of Clomipramine (clomipramine) include: brain zaps, nausea, insomnia, anxiety, dizziness, electric shocks. Symptom severity varies by individual, dose, and duration of use.

clomipramine

TCAFDA 1989

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Boxed Warning

Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.

Overview

Clomipramine is a tricyclic antidepressant with the strongest serotonin reuptake inhibition of all TCAs. It is the only TCA FDA-approved for obsessive-compulsive disorder (OCD) and is considered a gold-standard treatment for severe OCD.

Common Doses

25mg, 50mg, 75mg, 100mg

Formulations

Capsules: 25mg, 50mg, 75mg

Pregnancy

Category C (risk cannot be ruled out)

Mechanism of Action

Potent inhibitor of serotonin reuptake (most serotonergic TCA) and moderate inhibitor of norepinephrine reuptake. Its metabolite desmethylclomipramine is a potent norepinephrine reuptake inhibitor. Also has anticholinergic, antihistaminic, and alpha-adrenergic blocking activity.

Taper Notes

Most serotonergic of the TCAs; withdrawal often resembles SSRI discontinuation in addition to anticholinergic rebound. Capsules can be opened for bead counting where finer increments are needed.

Maudsley Deprescribing Guidance

Strong SERT inhibition produces SSRI-like withdrawal in addition to cholinergic rebound. Apply slow hyperbolic reductions (~10% per step) over months; bead counting from capsules supports sub-strength dosing.

Common Withdrawal Symptoms

brain zapsnauseainsomniaanxietydizzinesselectric shocks

Interactions & Safety

Drug Interactions

MAOIs — contraindicated (serotonin syndrome and hypertensive crisis)
CYP2D6 inhibitors significantly increase clomipramine levels
CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) increase levels — fluvoxamine can cause dramatic elevations

Food Interactions

Food does not significantly affect absorption
Grapefruit juice may increase levels
Avoid alcohol (additive CNS depression)

Contraindications

MAOIs within 14 days
Acute recovery period post-myocardial infarction
Known hypersensitivity to clomipramine or other TCAs

Toxicity

Cardiotoxic in overdose (QRS widening, arrhythmias). Seizures (dose-dependent, especially >250mg/day). Serotonin syndrome risk. Anticholinergic toxicity.

Pharmacokinetics

ADME Profile

Absorption

Well absorbed after oral administration. Extensive first-pass metabolism; bioavailability ~50%. Tmax 2–6 hours. Food does not significantly affect absorption.

Distribution

~17 L/kg

Metabolism

Hepatic via CYP2D6, CYP1A2, CYP2C19, and CYP3A4 to the active metabolite desmethylclomipramine and hydroxylated metabolites.

Elimination

Renal (~51–60% as metabolites) and fecal (~24–32%). Less than 1% excreted unchanged in urine.

Protein Binding

~97–98%

Clearance

Apparent oral clearance variable; auto-inhibition of CYP2D6 with chronic dosing.

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