[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/) › Clomipramine [Pharmacology](https://durgical.com/en/pharmacology/) · [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/) # 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 - Class: [Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/) - Transporter: Serotonin transporter (SERT) - ATC code: N06AA04 - WHO Model List of Essential Medicines ⇄**Serotonin transporter (SERT)**Clomipramine ⓘ 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). **Target in 3D:** Serotonin transporter (SERT). PDB structure 7LWD (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7LWD) · Drag to rotate · pinch to zoom ## 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 ### Serious (rare, important) - Seizures (the main risk identified before marketing) - Fatal toxicity in overdose (arrhythmias, QRS widening, coma) - Suicidal thoughts and behaviour in young people (boxed warning) - Serotonin syndrome - Hyperthermia - Angle-closure glaucoma ## 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. ## Memory aid CLOMIPRAMINE: «CLeans Obsessions», the tricyclic for OCD, but watch for seizures. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/clomipramine/) ## Related drugs - [Amitriptyline](https://durgical.com/en/pharmacology/amitriptyline/) - [Fluoxetine](https://durgical.com/en/pharmacology/fluoxetine/) [← Back to the class: Tricyclic antidepressants (TCAs)](https://durgical.com/en/pharmacology/classes/tricyclic-antidepressants/) 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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bf37fdc5-f579-48c9-baa3-8e516ac71a33) (DailyMed (U.S. National Library of Medicine), 2025); [Clomipramine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a697002.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/?query=clomipramine) (World Health Organization, 2025); [7LWD: Cryo-EM structure of the wild-type human serotonin transporter complexed with vilazodone, imipramine and 15B8 Fab](https://www.rcsb.org/structure/7LWD) (RCSB Protein Data Bank, 2021). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/clomipramine/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/clomipramine/