Clomipramine Withdrawal & Tapering Guide
clomipramine
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
In short
Clomipramine (clomipramine) is a TCA with a half-life of 19–37 hours. Strong serotonergic TCA. It is also sold as Anafranil.
- Class
- TCA
- Half-life
- 19–37 hours
- Common doses
- 25mg, 50mg, 75mg, 100mg
Educational reference only. Dose changes are decided with the prescriber who knows your history.
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.
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Other Drug Profiles
The arithmetic of a proportional reduction
The Maudsley Deprescribing Guidelines and NICE NG222 describe reducing TCA medications by a proportion of the previous dose rather than by a fixed amount, so each cut is smaller than the last. The table shows what that arithmetic produces at 10% per step, using 50 mg only as a worked example. How large each step is, how long it is held, and whether this pattern applies at all are decisions for the person and their prescriber.
| Step | % of starting dose | Worked example (50 mg start) |
|---|---|---|
| Start | 100% | 50 mg |
| Step 1 | 90% | 45 mg |
| Step 2 | 81% | 40.5 mg |
| Step 3 | 73% | 36.5 mg |
| Step 4 | 66% | 32.8 mg |
| Step 5 | 59% | 29.5 mg |
| Step 6 | 53% | 26.6 mg |
| Step 7 | 48% | 23.9 mg |
| Step 8 | 43% | 21.5 mg |
This is an illustration of a published method, not a schedule for anyone. It does not account for how long you have taken Clomipramine, your current dose, formulation, or history. TaperCommunity does not recommend doses or dose changes; those are agreed with your prescriber.
Frequently asked questions about Clomipramine
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.
How should I taper off Clomipramine (clomipramine)?
Strong serotonergic TCA. Withdrawal can be severe. Capsules can be opened for bead counting. Due to strong serotonin reuptake inhibition, withdrawal can resemble SSRI discontinuation. Slow hyperbolic taper recommended.
Can I stop Clomipramine cold turkey?
Stopping Clomipramine abruptly is not recommended. Its half-life is 19–37 hours, and the receptor adaptations built up during treatment do not reverse at that speed, so a sudden stop tends to produce the sharpest withdrawal. Prescribing guidance favours gradual, proportional reductions agreed with your prescriber.
How long does Clomipramine stay in your system?
Clomipramine (clomipramine) has a half-life of 19–37 hours. A drug is mostly cleared after about five half-lives, so Clomipramine is largely out of the body roughly 4 to 8 days after the last dose, longer in older adults or with liver or kidney impairment. Withdrawal symptoms often begin before the drug has fully cleared and continue after it has, because the adaptations the brain made during treatment reverse more slowly than the drug leaves the blood.
Recent discussions about Clomipramine
What members tapering Clomipramine are asking and reporting right now. Personal experience, not medical advice.
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.