Clomipramine Tapering Guide
clomipramine
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.
25mg, 50mg, 75mg, 100mg
Capsules: 25mg, 50mg, 75mg
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
Strong serotonergic TCA. Withdrawal can be severe. Capsules can be opened for bead counting.
Hyperbolic Tapering Guidance
Due to strong serotonin reuptake inhibition, withdrawal can resemble SSRI discontinuation. Slow hyperbolic taper recommended.
Summary written by TaperCommunity, informed by the Maudsley Deprescribing Guidelines (Horowitz & Taylor) and related literature — see Sources & References below. Not affiliated with or endorsed by the Maudsley.
Common Withdrawal Symptoms
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
Well absorbed after oral administration. Extensive first-pass metabolism; bioavailability ~50%. Tmax 2–6 hours. Food does not significantly affect absorption.
~17 L/kg
Hepatic via CYP2D6, CYP1A2, CYP2C19, and CYP3A4 to the active metabolite desmethylclomipramine and hydroxylated metabolites.
Renal (~51–60% as metabolites) and fecal (~24–32%). Less than 1% excreted unchanged in urine.
~97–98%
Apparent oral clearance variable; auto-inhibition of CYP2D6 with chronic dosing.
Need a clinician who understands tapering?
Browse our map of deprescribing-informed providers worldwide.
Other Drug Profiles
Sources & References
Clomipramine (clomipramine) information on this page is sourced from peer-reviewed research, regulatory bodies, clinical guidelines, and patient-advocacy organizations.
Encyclopedic & chemical databases
Neutral, high-authority entity references.
Peer-reviewed research
Primary literature cited in this taper guide.
- Horowitz MA, Taylor D 2019 — Tapering of SSRI treatment to mitigate withdrawal symptoms (hyperbolic taper) (The Lancet Psychiatry)
- Davies J, Read J 2019 — A systematic review into the incidence, severity and duration of antidepressant withdrawal effects (Addictive Behaviors)
- Framer A 2021 — The patient voice: an exploration of the experience of withdrawal from antidepressants (Therapeutic Advances in Psychopharmacology)
Clinical guidelines
Evidence-based deprescribing and prescribing standards.
Deprescribing-specific resources
Clinician-facing references on tapering protocols.
- Deprescribing.org — Evidence-based deprescribing algorithms from the Bruyère Research Institute
- Royal College of Psychiatrists — Stopping antidepressants — UK clinical guidance on safely discontinuing antidepressants
Patient-advocacy & lived-experience
Long-running communities documenting withdrawal experience.
- Surviving Antidepressants — tapering forum — Long-running community archive of antidepressant taper experiences
- Inner Compass Initiative — Withdrawal Project — Peer-led resources for psychiatric drug withdrawal
- Mad in America — antidepressant withdrawal archive — Journalism and personal narratives on SSRI/SNRI discontinuation
- RxISK — adverse drug reaction reporting — Independent database of patient-reported adverse effects
TaperCommunity does not provide medical advice. Always consult a qualified prescriber before adjusting psychiatric medication.