DangerousContraindicated
5-HTP
5-HTP increases serotonin synthesis and can precipitate serotonin syndrome with clomipramine.
Recommendation: Avoid 5-HTP with clomipramine.
Clomipramine
Prescription ·Strong evidence ·Reviewed May 2026
Clomipramine is a tricyclic antidepressant approved for obsessive-compulsive disorder. It has strong serotonin reuptake inhibition plus typical tricyclic anticholinergic, antihistaminic, alpha-adrenergic, cardiac conduction, and seizure-threshold effects. It carries the antidepressant boxed warning for suicidal thoughts and behaviors in pediatric and young adult patients.
What it's good for
- Treatment of obsessive-compulsive disorder1
- Reduction in obsessions and compulsions
- Occasional specialist use for treatment-resistant depression or anxiety-spectrum symptoms
The bottom line
Evidence rating strong. Most-documented uses: treatment of obsessive-compulsive disorder, reduction in obsessions and compulsions, occasional specialist use for treatment-resistant depression or anxiety-spectrum symptoms. 3 sources indexed (2005–2025), with 4 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Clomipramine inhibits serotonin and norepinephrine reuptake, with relatively potent serotonin transporter inhibition compared with many older TCAs. Its active metabolite desmethylclomipramine contributes norepinephrine reuptake inhibition. Antagonism at muscarinic, histamine H1, and alpha-1 adrenergic receptors explains dry mouth, constipation, sedation, weight gain, and orthostatic hypotension, while sodium-channel effects can worsen cardiac conduction in overdose or susceptible patients.1,2
Class
Tricyclic antidepressant and serotonin reuptake inhibitor
Absorption
Water-soluble; take with food
Dosing
Dosing & protocol.
Common range
Start 25 mg once daily, usually with meals, and titrate gradually toward 100 mg/day during the first 2 weeks. Usual adult range is 100-250 mg/day; maximum recommended adult dose is 250 mg/day.
Recommended form
Oral capsule, often divided during titration and then consolidated at bedtime if tolerated
Taking with meals during titration can reduce gastrointestinal adverse effects. Once stabilized, total daily dosing at bedtime may reduce daytime sedation.3
Safety
Full safety detail.
Side effects
- Dry mouth
- Constipation
- Blurred vision
- Urinary retention
- Sedation
- Weight gain
- Orthostatic hypotension
- Sexual dysfunction
- Sweating
- QT prolongation or conduction delay in susceptible patients
- Seizures, especially at higher doses
- Serotonin syndrome with serotonergic agents
- Withdrawal symptoms if stopped abruptly
Contraindications
- Hypersensitivity to clomipramine or other dibenzazepine TCAs1,2
- Concurrent use with an MAOI, linezolid, or intravenous methylene blue3
- Do not use during acute recovery after myocardial infarction
- Avoid in uncontrolled narrow-angle glaucoma or clinically significant urinary retention unless specialist-supervised
Interactions
Interaction records.
DangerousContraindicated
L-Tryptophan
Supplemental L-Tryptophan can increase serotonin production during clomipramine therapy.
Recommendation: Avoid L-Tryptophan supplements while taking clomipramine.
DangerousContraindicated
St. John's Wort
St. John's Wort can add serotonergic activity and can alter metabolism of many drugs.
Recommendation: Do not combine St. John's Wort with clomipramine.
SeriousCaution
Ginkgo Biloba
Ginkgo has case reports of seizures and may increase bleeding tendency. Clomipramine can lower seizure threshold and may increase bleeding risk through serotonergic effects.
Recommendation: Avoid in patients with seizure history or high-dose clomipramine; use caution in patients with bleeding risk.
Sources
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Reviews & position papers
2- 1Practice guideline for the treatment of patients with obsessive-compulsive disorderNeeds reviewNo linkAmerican Psychiatric Association · American Journal of Psychiatry · 2007
Guideline recognizes clomipramine efficacy for OCD while emphasizing tolerability and safety concerns relative to SSRIs.
- 2Tricyclic antidepressant poisoningNeeds reviewNo linkThanacoody HKR, Thomas SHL · Toxicological Reviews · 2005
Review describes sodium-channel blockade, arrhythmia, seizure, and anticholinergic toxicity relevant to clomipramine overdose and high-risk patients.
Reference material
1- 3CLOMIPRAMINE HYDROCHLORIDE capsules, US Prescribing InformationNeeds reviewURLU.S. National Library of Medicine · DailyMed · 2025
Labeling describes OCD indication, 25 mg starting dose, maximum adult dose of 250 mg/day, MAOI contraindication, and suicide warning.
Keep exploring
Deep dives & adjacent profiles.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Clomipramine in NutriStack.
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.