SURMONTIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SURMONTIL (SURMONTIL).
Tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin, with anticholinergic, antihistaminergic, and alpha-adrenergic blocking properties.
| Metabolism | Hepatic via CYP2D6 and CYP3A4; active metabolite desmethyltrimipramine. |
| Excretion | Renal excretion of metabolites accounts for approximately 70-80% of elimination, with about 20-30% excreted in feces via biliary elimination. Unchanged drug in urine is less than 5%. |
| Half-life | 11-27 hours (mean approximately 20 hours) for the parent drug; the active metabolite desmethyltrimipramine has a half-life of 15-30 hours. Steady-state is achieved within 5-7 days. |
| Protein binding | Approximately 95% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 15-30 L/kg, indicating extensive tissue distribution and accumulation in peripheral compartments. |
| Bioavailability | Oral: 30-60% due to first-pass metabolism; IM: Not available in the US; not recommended for clinical use. |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; sedation occurs within 30-60 minutes. IM: Not routinely used for depression. |
| Duration of Action | Antidepressant effect persists for several weeks; sedative effects last 6-8 hours after a single dose. Withdrawal symptoms may occur if abruptly discontinued after prolonged therapy. |
| Molecular Weight | 294.4 |
| Action Class | Tricyclic antidepressants |
| Brand Substitutes | Sizonorm Plus Tablet |
50-75 mg/day orally in divided doses, increase gradually to 150-300 mg/day. Maximum 300 mg/day. Single bedtime dose may be used for maintenance (50-150 mg).
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (GFR <30 mL/min). Consider dose reduction based on tolerability due to potential accumulation of metabolites. |
| Liver impairment | Child-Pugh A: No adjustment required. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Use contraindicated (consider alternative). |
| Pediatric use | Not recommended for children under 12 years. For adolescents 12-18 years: 25-50 mg/day initially, increase gradually to 50-100 mg/day in divided doses. Maximum 100 mg/day. |
| Geriatric use | Initial dose 25-50 mg/day in divided doses, increase slowly. Maintenance often lower: 30-100 mg/day. Monitor for orthostatic hypotension, sedation, and anticholinergic effects. |
| 1st trimester | Limited human data; animal studies show fetotoxicity at high doses. Avoid unless clearly needed. |
| 2nd trimester | May be used if benefit outweighs risk; monitor for maternal anticholinergic effects. |
| 3rd trimester | Neonatal withdrawal (irritability, tachycardia) and anticholinergic effects possible. Avoid near term if possible. |
Clinical note
Comprehensive clinical and safety monograph for SURMONTIL (SURMONTIL).
| Placental transfer | Trimipramine crosses the placenta; fetal levels are approximately 50-80% of maternal levels. |
| Breastfeeding | Trimipramine is excreted into breast milk in small amounts; infant serum levels are low but may accumulate. Monitor infant for drowsiness, poor feeding, and irritability. Use with caution, especially in neonates or premature infants. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
Hypersensitivity to trimipramine or any componentConcomitant use with MAOIs (within 14 days)Acute recovery phase of myocardial infarctionConcurrent use of linezolid or intravenous methylene blue
| Precautions | CNS depression; cardiac toxicity (QT prolongation, arrhythmias); seizures; angle-closure glaucoma; urinary retention; hyponatremia; serotonin syndrome; withdrawal symptoms; impaired cognitive/motor function. |
| Food/Dietary | Avoid tyramine-rich foods (aged cheese, cured meats, pickled fish) if taking MAOIs concurrently; otherwise no significant food interactions. Grapefruit juice may increase side effects; avoid excessive caffeine. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Risk of neonatal withdrawal symptoms (e.g., respiratory distress, jitteriness) and anticholinergic effects if used near term. Avoid in third trimester if possible. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, ECG, and signs of anticholinergic toxicity (e.g., constipation, urinary retention). Fetal monitoring: growth ultrasound, nonstress test in third trimester. Neonatal observation for withdrawal syndrome. |
| Fertility Effects | May cause hyperprolactinemia, galactorrhea, and menstrual irregularities with potential impact on ovulation. Limited data on male fertility; possible reversible effects on sperm parameters. |
| Clinical Pearls | Surmontil (trimipramine) is a tricyclic antidepressant with strong sedative properties, often used for depression with insomnia. It has lower anticholinergic effects than amitriptyline but may cause orthostatic hypotension. Monitor ECG in elderly patients due to risk of QT prolongation. |
| Patient Advice | Take at bedtime to minimize daytime drowsiness. · Avoid driving or operating machinery until you know how this medication affects you. · Do not stop abruptly; taper under medical supervision to avoid withdrawal symptoms. · Report any suicidal thoughts or mood changes immediately. · Avoid alcohol and other CNS depressants. |