Anafranil (Clomipramine) Tapering Guide

Dosage

Clomipramine is typically supplied as 25 mg and 50 mg capsules that cannot be split. Doses below 25 mg — where the occupancy curve is steepest — usually need a compounded oral liquid.

High serotonergic activity and a high withdrawal-risk profile mean slow hyperbolic steps. Going slowly also helps separate withdrawal from returning OCD symptoms.

Dose vs occupancy

This taper is spread across 46 gradual steps. The curve below shows why the last few milligrams matter most: at low doses, small dose changes produce large drops in serotonin-transporter occupancy.

What this shows: the non-linear relationship between dose and serotonin transporter (SERT) occupancy. The curve is flat at high doses — most transporters are already blocked, so a dose cut has little biological impact — and much steeper at low doses, where even a 1–2 mg reduction causes a disproportionately large drop in occupancy. Your taper steps are spaced along this curve so each step removes a similar amount of occupancy.

• 72%

  discontinued their antidepressant using hyperbolic tapering strips in a real-world study

  71% of the same people had previously tried to stop at least once and been unsuccessful; the study did not record which method those earlier attempts used. Figures come from tapering-strip research and may not generalise to every taper.

  Source: Groot et al., Therapeutic Advances in Psychopharmacology 2021

• 56 days

  median taper length in that tapering-strip study — not a target; many people taper over 6–12 months or longer

  This median reflects tapering-strip use in one study. Your timeline depends on how long you have taken the medication, your withdrawal symptoms, and previous attempts — slower is often safer.

  Source: Groot et al., Therapeutic Advances in Psychopharmacology 2021

• 10%

  serotonin transporter occupancy per tapering step

  This linear reduction prevents withdrawal. Slower, more gradual tapering over several months has shown greater success in reducing withdrawal symptoms than short tapers.

  Source: Horowitz et al., The Lancet Psychiatry 2019

1. [1]Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. The Lancet Psychiatry 2019.doi:10.1016/S2215-0366(19)30032-XProposes hyperbolic dose reduction based on receptor-occupancy curves; the methodological basis of every modern taper calculator.
2. [2]Horowitz MA, Taylor D. The Maudsley Deprescribing Guidelines. Wiley 2024.doi:10.1002/9781394291052Per-drug operational manual for hyperbolic tapering across SSRIs, SNRIs, benzodiazepines, gabapentinoids, and antipsychotics.
3. [3]Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects. Addictive Behaviors 2019.doi:10.1016/j.addbeh.2018.08.027Systematic review: 56% of people who discontinue antidepressants experience withdrawal effects; 46% rate them as severe.
4. [4]Henssler J et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. The Lancet Psychiatry 2024.doi:10.1016/S2215-0366(24)00133-0Meta-analysis of 79 studies (≈21,000 patients): pooled incidence of discontinuation symptoms ~31%; severe symptoms ~2.8%.
5. [5]Groot PC, van Os J. Successful use of tapering strips for hyperbolic reduction of antidepressant dose: a cohort study. Therapeutic Advances in Psychopharmacology 2021.doi:10.1177/2045125321103932772% of patients successfully discontinued antidepressants after switching to the hyperbolic model; 71% had previously failed to come off without tapering strips.
6. [6]Groot PC, van Os J. Antidepressant tapering strips to help people come off medication: real-world outcomes. Therapeutic Advances in Psychopharmacology 2023.doi:10.1177/20451253231171518Of 1,194 patients using hyperbolic taper strips after previous failed attempts, ~71% successfully discontinued their antidepressant.
7. [7]Framer A. What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications. Therapeutic Advances in Psychopharmacology 2021.doi:10.1177/2045125321991274Describes the "windows and waves" pattern of withdrawal recovery and supports patient-led pacing.
8. [8]Hengartner MP et al. Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives. Therapeutic Advances in Psychopharmacology 2020.doi:10.1177/2045125320967183Descriptive analysis of 69 protracted withdrawal cases: median duration 79 weeks; 47% report suicidality during withdrawal.
9. [9]Cosci F, Chouinard G. Acute and persistent withdrawal syndromes following discontinuation of psychotropic medications. Psychotherapy and Psychosomatics 2020.doi:10.1159/000506868Taxonomy distinguishing new withdrawal symptoms, rebound, and persistent post-withdrawal disorder; the standard framework for withdrawal vs. relapse.
10. [10]Kalfas M et al. Incidence and Nature of Antidepressant Discontinuation Symptoms. JAMA Psychiatry 2025.doi:10.1001/jamapsychiatry.2025.1362Recent meta-analysis: dizziness was the most common discontinuation symptom in the first 2 weeks after stopping antidepressants, followed by nausea, vertigo, and nervousness.
11. [11]Gabriel M, Sharma V. Antidepressant discontinuation syndrome. Canadian Medical Association Journal 2017.doi:10.1503/cmaj.160991Clinical review of antidepressant discontinuation syndrome: onset within days of dose reduction, typical symptom course, and management.
12. [12]Papp A, Onton J. Brain Zaps: An Underappreciated Symptom of Antidepressant Discontinuation. The Primary Care Companion for CNS Disorders 2018.doi:10.4088/pcc.18m02311Characterises "brain zaps" — brief electric-shock sensations — as a common antidepressant discontinuation symptom.
13. [13]Wang J, Cosci F. Acute and persistent withdrawal syndromes following discontinuation of antidepressants in children and adolescents: a systematic review. Therapeutic Advances in Psychopharmacology 2025.doi:10.1177/20451253251404780Systematic review of acute and persistent antidepressant withdrawal syndromes; reinforces reducing only when stable and under supervision.
14. [14]Horowitz M, Taylor D. Distinguishing relapse from antidepressant withdrawal: clinical practice and antidepressant discontinuation studies. BJPsych Advances 2022.doi:10.1192/bja.2021.62Frames how clinicians can distinguish antidepressant withdrawal from relapse of the underlying condition.
15. [15]Sørensen A, Ruhé HG, Munkholm K. The relationship between dose and serotonin transporter occupancy of antidepressants — a systematic review. Molecular Psychiatry 2021.doi:10.1038/s41380-021-01285-wSystematic review of dose–SERT-occupancy relationships across antidepressants; confirms the hyperbolic curve underlying proportional tapering.
16. [16]Reeve R, Turner JR. Pharmacodynamic models: parameterizing the Hill equation, Michaelis-Menten, the logistic curve, and relationships among these models. Journal of Biopharmaceutical Statistics 2013.doi:10.1080/10543406.2012.756496Explains how the Hill equation, Michaelis-Menten, and logistic models relate — the mathematical basis for the occupancy curve used here.
17. [17]Preskorn SH. The use of biomarkers in psychiatric research: how serotonin transporter occupancy explains the dose-response curves of SSRIs. Journal of Psychiatric Practice 2012.LinkShows how SERT occupancy explains the non-linear dose–response curves of SSRIs.
18. [18]Cohrs D, Shapiro B. The relationship between SERT occupancy and extracellular serotonin concentration is hyperbolic, not linear: implications for safely tapering SRI antidepressants. SSRN (preprint) 2026.doi:10.2139/ssrn.6176553Argues the SERT-occupancy to serotonin relationship is itself hyperbolic, reinforcing proportional (hyperbolic) tapering.
19. [19]Moncrieff J et al. Evidence on antidepressant withdrawal: an appraisal and reanalysis of a recent systematic review. Psychological Medicine 2025.doi:10.1017/S0033291725100652Reappraisal of recent withdrawal-incidence evidence; relevant to how withdrawal rates are interpreted.
20. [20]Wilson E, Lader M. A review of the management of antidepressant discontinuation symptoms. Therapeutic Advances in Psychopharmacology 2015.doi:10.1177/2045125315612334Practical review of how to manage antidepressant discontinuation symptoms, including tapering and reinstatement.
21. [21]Groot PC, van Os J. Outcome of antidepressant drug discontinuation with tapering strips after 1–5 years. Therapeutic Advances in Psychopharmacology 2020.doi:10.1177/2045125320954609Long-term follow-up (1–5 years) of patients who discontinued antidepressants using hyperbolic taper strips.
22. [22]Gury C, Cousin F. Pharmacokinetics of SSRI antidepressants: half-life and clinical applicability. L'Encéphale 1999.LinkHalf-life data for SSRIs — explains why short-half-life drugs (paroxetine, venlafaxine) provoke faster withdrawal.
23. [23]Mayo Clinic. Antidepressant withdrawal: Is there such a thing?. Mayo Clinic — Expert Answers 2024.LinkPatient-facing explainer on antidepressant discontinuation symptoms and gradual tapering.
24. [24]NHS Scotland — Right Decision Service. Antidepressants — quality prescribing: difficulty withdrawing from an SSRI/SNRI. NHS Scotland 2024.LinkNHS Scotland guidance on recognising and managing difficulty withdrawing from SSRIs/SNRIs.
25. [25]The Carlat Psychiatry Report. Clinical pearls for hyperbolic tapering of psychiatric medications in older adults. The Carlat Report 2024.LinkPractical clinical pearls for applying hyperbolic tapering, including in older adults.
26. [26]Royal College of Psychiatrists. Stopping antidepressants — information for patients and carers. Royal College of Psychiatrists 2024.LinkRCPsych patient-facing guidance on coming off antidepressants safely.
27. [27]National Institute for Health and Care Excellence (NICE). Depression in adults: treatment and management. NICE guideline [NG222]. NICE 2022.LinkUK national guideline endorsing proportional (hyperbolic) tapering and the use of liquid formulations to enable small final doses.
28. [28]Royal College of Psychiatrists. Stopping antidepressants — position statement (CR225). Royal College of Psychiatrists 2020.LinkRCPsych acknowledges withdrawal can be severe and long-lasting; recommends slow, individualised tapers.
29. [29]NHG et al. Multidisciplinary document: Discontinuation of SSRIs and SNRIs (2018; revised 2023). Multidisciplinary Document (Netherlands) 2018.LinkFirst national guideline to explicitly endorse hyperbolic tapering and the use of taper strips (compounded by Regenboog Apotheek).
30. [30]Medicines and Healthcare products Regulatory Agency (MHRA). Summary of Product Characteristics — SSRI and SNRI products (UK). electronic Medicines Compendium (emc) 2023.LinkAuthoritative UK formulary data (tablet strengths, oral solutions) used to validate the UK region in the calculator.
31. [31]U.S. Food and Drug Administration. Prescribing information (Structured Product Labeling) for SSRI/SNRI products. FDA / DailyMed 2024.LinkAuthoritative US formulary data (tablet strengths, oral solutions/concentrates) used to validate the US region in the calculator.
32. [32]Health Canada. Health Canada — Drug Product Database. Health Canada 2024.LinkAuthoritative Canadian formulary data used to validate the Canada region in the calculator.
33. [33]Therapeutic Goods Administration (TGA). Therapeutic Goods Administration — Australian Register of Therapeutic Goods (ARTG). TGA / ARTG 2024.LinkAuthoritative Australian formulary data used to validate the Australia region in the calculator.
34. [34]College ter Beoordeling van Geneesmiddelen (CBG-MEB). CBG-MEB — Medicines Information Bank (Netherlands). CBG-MEB 2024.LinkAuthoritative Dutch formulary data; cross-checked with Regenboog Apotheek taper-strip availability.
35. [35]Regenboog Apotheek, Cinetto. Taperingstrip.com — Regenboog Apotheek. Patient resource (NL) 2024.LinkPioneer of standardised taper strips referenced in the Dutch national guideline.