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Maprotiline (Ludiomil)

Tetracyclic • Last reviewed 2025-09-27

General information

Maprotiline is a tetracyclic antidepressant with strong norepinephrine reuptake inhibition and antihistamine activity. It is useful for melancholic presentations but carries a higher seizure risk than most TCAs.

Therapeutic drug monitoring is essential; plasma levels above 600 ng/mL are linked to generalized seizures and cardiotoxicity.

Compared with tertiary amine TCAs, maprotiline causes less anticholinergic burden but more pronounced weight gain and sedation.

Baseline ECG, seizure history, and review of concomitant threshold-lowering agents are important before initiation.

Dosing & administration

Start 25–50 mg at bedtime; increase by 25 mg every 3–7 days to 100–150 mg/day.

Maximum 225 mg/day; avoid rapid titration to minimize seizure risk.

Lower doses (25–75 mg) may suffice for elderly or hepatic impairment.

Mechanism of action

Selective norepinephrine reuptake inhibition with minimal serotonergic effect; antagonizes histamine H1 receptors leading to sedation.

Metabolism & pharmacokinetics

Half-life ~52 h; metabolized by CYP2D6 to active metabolites excreted renally. Steady state reached in 10 days.

Drug interactions

Avoid MAOIs and cisapride (serotonin/QT risk).

CYP2D6 inhibitors (fluoxetine, paroxetine) elevate levels; enzyme inducers decrease efficacy.

Additive seizure risk with bupropion, tramadol, antipsychotics.

Monitoring & safety checks

Discontinuation guidance

Taper gradually over ≥4 weeks to avoid cholinergic rebound, insomnia, and relapse.

References

  1. Maprotiline Prescribing Information — DailyMed
  2. Therapeutic drug monitoring of maprotiline — Therapeutic Drug Monitoring (2022)
  3. CANMAT guidance on tetracyclic antidepressants — Canadian Journal of Psychiatry (2024)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.