Pharmacology · Tricyclic antidepressants (TCAs)
Clomipramine !
A strongly serotonergic tricyclic on the WHO list for obsessive-compulsive disorder. Seizures are its main risk, plus the dangers of tricyclic overdose.
Updated 2026-11-01
The figure shows imipramine, the tricyclic of which clomipramine is the chlorinated analogue, bound to human SERT (cryo-EM, with vilazodone and an antibody fragment).
Mechanism of action
Clomipramine inhibits serotonin reuptake, which is thought to explain its effect on obsessions and compulsions; its main active metabolite is desmethylclomipramine. Like other tricyclics, it also blocks muscarinic, H1 and alpha-1 receptors and, in overdose, cardiac sodium channels.
- Clomipramine blocks the serotonin transporter strongly
- Its active metabolite desmethylclomipramine prolongs the effect
- Muscarinic, H1 and alpha-1 block cause typical tricyclic effects
- Obsessions and compulsions ease over weeks
Pharmacokinetics
- Absorption
- By mouth; food does not change bioavailability much
- Metabolism
- In the liver to desmethylclomipramine, also active
- Half-life
- Clomipramine about 19 to 37 hours and desmethylclomipramine about 54 to 77 hours after a single dose; longer at high exposure
Indications
- Obsessive-compulsive disorder
Adverse effects
Common
- Dry mouth, constipation, urinary problems (anticholinergic)
- Somnolence, tremor, dizziness
- Sexual dysfunction, very common in men
- Sweating and weight gain
Contraindications
- MAO inhibitors for psychiatric use, or within 14 days of stopping either drug; not started during linezolid or intravenous methylene blue
- Acute recovery period after myocardial infarction
- Hypersensitivity to clomipramine or other tricyclics
Key interactions
- MAO inhibitors, triptans, tramadol, fentanyl, lithium, St John's wort
- Serotonin syndrome
- CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine)
- Higher tricyclic levels and toxicity
- Drugs that lower the seizure threshold
- Higher seizure risk
- Anticholinergic drugs and CNS depressants
- Additive anticholinergic effects and sedation
What is monitored
- Seizure risk factors (epilepsy, head injury, alcohol withdrawal)
- ECG in heart disease or older adults
- Anticholinergic effects and orthostatic blood pressure
- Mood and suicidal thoughts
Administration and safety
- Given by mouth; early in treatment the label advises giving it with meals to reduce stomach upset
- People at risk of suicide get the smallest practical supply because overdose can be fatal
- Stopped gradually
Nursing care
- Ask about seizures and other seizure risk factors before starting
- Check orthostatic blood pressure and anticholinergic effects (constipation, urinary retention)
- Ask openly about sexual side effects, which are common
- Know the signs of tricyclic overdose and limit the amount available at home
Pregnancy and breastfeeding
Used in pregnancy only when the benefit justifies the possible risk; jitteriness, tremor and seizures have been reported in exposed newborns.
Test yourself
Think of the answer, then tap the question to see it.
Which tricyclic antidepressant is used for obsessive-compulsive disorder, and why does it work?
Clomipramine. Its serotonin reuptake block is thought to explain its effect on obsessions and compulsions.
What was identified as the most significant risk of clomipramine before it was marketed?
Seizures, with a cumulative risk that rises with exposure.
Why is clomipramine contraindicated after a recent myocardial infarction?
Like other tricyclics it can cause arrhythmias and conduction changes, so it is not used in the acute recovery period after an infarction.
Related drugs
← Back to the class: Tricyclic antidepressants (TCAs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - CLOMIPRAMINE HYDROCHLORIDE capsule (DailyMed (U.S. National Library of Medicine), 2025); Clomipramine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025); 7LWD: Cryo-EM structure of the wild-type human serotonin transporter complexed with vilazodone, imipramine and 15B8 Fab (RCSB Protein Data Bank, 2021).
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Representative model, for educational purposes only.