Trimipramine

Trimipramine is a tricyclic antidepressant (TCA) used in the treatment of major depressive disorder. It was developed in the mid-20th century and marketed under brand names such as Surmontil. Availability varies by country, and use may depend on local guidelines and prescribing practices.

Mechanism of action and properties: Like other TCAs, trimipramine is believed to exert antidepressant effects primarily through inhibition of the reuptake of serotonin and norepinephrine. It also acts as an antagonist at several receptor sites, including histamine H1 and alpha-1 adrenergic receptors, and to a lesser extent muscarinic acetylcholine receptors. The combination of monoamine reuptake inhibition and receptor antagonism contributes to both therapeutic effects and the drug’s characteristic side-effect profile. Sedation is a notable feature, largely due to antihistaminic activity.

Pharmacokinetics: Trimipramine is taken orally and is extensively metabolized in the liver to active and inactive metabolites, including desmethyltrimipramine. It has a relatively long duration of action and is primarily eliminated via hepatic pathways, with excretion in urine and feces. Time to clinical antidepressant response typically spans several weeks.

Clinical use and considerations: Trimipramine is indicated for major depressive disorder and may be used in patients with coexisting insomnia or anxiety due to its sedative properties. It is generally considered after other antidepressants have been tried or when patients can tolerate its side-effect profile. Dosing is individualized and gradual titration is common.

Adverse effects and safety: The medication carries typical TCA-associated risks, including anticholinergic effects (dry mouth, constipation, blurred vision), sedation, dizziness, and orthostatic hypotension. Cardiac effects such as tachycardia or conduction disturbances can occur, and there is a risk of serious toxicity in overdose. Caution is advised with concurrent QT-prolonging drugs and in patients with glaucoma, urinary retention, or cardiac disease.

Interactions and contraindications: Trimipramine should not be used with monoamine oxidase inhibitors and requires caution with other CNS depressants and anticholinergic agents. As with other TCAs, it should be used with care in the elderly and in patients with heart rhythm abnormalities.