MAPROTILINE HYDROCHLORIDE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Maprotiline is a tetracyclic antidepressant that inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin, thereby increasing their synaptic concentrations; it also has mild anticholinergic activity and blocks histamine H1 receptors.
| Metabolism | Hepatic metabolism primarily via CYP2D6, with minor contributions from CYP1A2 and CYP3A4; major metabolites include desmethylmaprotiline and maprotiline N-oxide. |
| Excretion | Primarily renal (70-80% as metabolites, <5% unchanged); biliary/fecal (20-30%) |
| Half-life | Terminal elimination half-life approximately 27-58 hours (mean 43 hours); may be prolonged in elderly or hepatic impairment; allows once-daily dosing at steady state within 7-14 days |
| Protein binding | 88% bound primarily to alpha-1-acid glycoprotein and albumin |
| Volume of Distribution | Approximately 20-25 L/kg (range 15-30 L/kg); extensive tissue distribution including brain |
| Bioavailability | Oral: 70-90% with linear kinetics; IM: 100% |
| Onset of Action | Oral: 2-3 weeks for antidepressant effect; sedation occurs within hours |
| Duration of Action | Antidepressant effect: sustained with continued therapy; sedative effect: 6-8 hours peak, persists throughout dosing interval |
75-150 mg orally once daily; initial dose 25-75 mg/day, increase gradually. Maximum 225 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 50%. GFR <30 mL/min: use with caution, reduce dose by 75% or avoid. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: avoid use. |
| Pediatric use | Not recommended for children under 18 years due to lack of safety data. |
| Geriatric use | Initial dose 25 mg/day; increase slowly to minimum effective dose. Maximum 75 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome and hyperpyrexia Can lower seizure threshold.
| Breastfeeding | Excreted into breast milk in low concentrations; M/P ratio not available. Monitor infant for sedation, poor feeding, and weight gain. Use caution; generally considered acceptable for short-term, low-dose therapy. |
| Teratogenic Risk | First trimester: Limited human data; animal studies showed increased fetal anomalies at high doses. Second and third trimesters: Risk of neonatal withdrawal (irritability, respiratory depression) and anticholinergic effects. No definitive teratogenicity established. |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Maprotiline may increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Common Effects | Sedation |
| Serious Effects |
Hypersensitivity to maprotiline or any component of the formulation; concomitant use of MAOIs or within 14 days of MAOI therapy; recent myocardial infarction; history of seizure disorder; angle-closure glaucoma; urinary retention; severe hepatic or renal impairment; pregnancy (based on animal data).
| Precautions | May cause seizures, especially at high doses; use with caution in patients with seizure disorders. Increased risk of serotonin syndrome when used with other serotonergic agents. May worsen angle-closure glaucoma and urinary retention due to anticholinergic effects. May cause cardiovascular effects such as QT prolongation and arrhythmias. Avoid abrupt discontinuation to prevent withdrawal symptoms. |
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| Fetal Monitoring |
| Monitor maternal blood pressure, heart rate, and ECG for arrhythmias. Assess for anticholinergic side effects (constipation, blurred vision). Fetal monitoring for growth, amniotic fluid index, and biophysical profile in third trimester. Neonatal surveillance for withdrawal symptoms post-delivery. |
| Fertility Effects | Limited data; may cause menstrual irregularities and galactorrhea due to prolactin elevation. Effects on spermatogenesis in males not reported. Reversible upon discontinuation. |