clomipramin

Clomipramin, also spelled clomipramine, is a tricyclic antidepressant (TCA) used in the treatment of mood disorders and obsessive-compulsive disorder (OCD). It is generally considered after other treatments, such as selective serotonin reuptake inhibitors (SSRIs), have been ineffective or poorly tolerated.

Mechanism of action and pharmacology

Clomipramin inhibits the reuptake of serotonin more potently than norepinephrine, increasing serotonin signaling in the brain. It also has a broad pharmacologic profile, including antagonism of α1-adrenergic and histaminergic H1 receptors and anticholinergic effects. These properties contribute to its therapeutic effects as well as its side effect profile.

Medical uses

The primary indication for clomipramin is OCD, where it is effective in reducing obsessive and compulsive symptoms. It is also used for major depressive disorder and, in some settings, for anxiety disorders such as panic disorder or social phobia, typically when first-line therapies are not suitable or have failed. It may be employed off-label for other conditions, but its use is limited by tolerability concerns.

Adverse effects and safety

Common adverse effects include dry mouth, constipation, urinary retention, blurred vision, sedation, weight gain, dizziness, and orthostatic hypotension. Anticholinergic effects and sedation are prominent with many TCAs. Cardiac effects, including tachycardia and potential QT prolongation, raise risks in overdose or in patients with heart disease. Clomipramin can cause sexual dysfunction and may induce mood switching in bipolar disorder. It should not be used with monoamine oxidase inhibitors and requires caution with other serotonergic drugs due to risk of serotonin syndrome.

Pharmacokinetics and interactions

Clomipramin is absorbed orally and metabolized in the liver, forming active metabolites such as norclomipramine. The parent drug and its metabolites have relatively long half-lives. Interactions include contraindication with MAO inhibitors and potential interactions with SSRIs, other TCAs, and substances that affect liver enzymes. Caution is advised with alcohol and other CNS depressants.