maprotiline

Maprotiline is a tetracyclic antidepressant (TCA) approved for the treatment of major depressive disorder in various countries. It is sold under brand names such as Ludiomil and has a history dating back to the 1960s and 1970s, though its use has declined in many places due to safety and tolerability concerns.

Pharmacology and mechanism of action: Maprotiline primarily acts as a norepinephrine reuptake inhibitor, increasing synaptic norepinephrine. It also possesses antihistaminic and anticholinergic properties, which contribute to sedation and typical TCA-related side effects. Its serotonergic effects are less prominent than those of some other antidepressants.

Indications and usage: It is prescribed for depressive episodes and, in some settings, for associated anxiety symptoms. Because of its sedative properties, it is sometimes used when insomnia accompanies depression. Dosing is individualized based on response and tolerability.

Administration and dosage: Maprotiline is taken orally. Initial doses are typically low and titrated upward as needed, with gradual adjustments to achieve symptom control while monitoring for adverse effects. The total daily dose is given in a single dose or divided, depending on clinical judgment. Treatment response usually requires several weeks.

Side effects and safety: Common adverse effects include drowsiness or sedation, dry mouth, constipation, blurred vision, dizziness, and orthostatic hypotension. Anticholinergic effects and weight gain can occur. There is a risk of seizures, especially at higher doses or in overdose, and potential cardiac effects such as arrhythmias or QT prolongation, particularly in patients with underlying heart disease. Maprotiline should be used with caution in the elderly and in individuals with liver disease, glaucoma, urinary retention, or a history of seizures.

Contraindications and interactions: It is contraindicated with a history of seizures, recent myocardial infarction, or significant hepatic impairment, and generally avoided with monoamine oxidase inhibitors (MAOIs). Concomitant use with other CNS depressants, alcohol, or other QT-prolonging drugs requires caution due to additive effects and risk of arrhythmias.

Pharmacokinetics: Maprotiline is absorbed orally and undergoes hepatic metabolism, with elimination via urine and feces. Its pharmacokinetic profile supports once-daily or divided dosing, depending on the clinical scenario.