trimipramine

General Information

Trimipramine (brand Surmontil; generics) is a tricyclic antidepressant (TCA) indicated for the relief of symptoms of depression. It is often characterized by a sedating, anxiety-reducing clinical profile compared with more “activating” TCAs (label/clinical).

TCAs have a narrow therapeutic index and are dangerous in overdose; this overdose risk is one reason they are generally positioned after SSRIs and SNRIs in major depressive disorder guidelines (APA/CANMAT/clinical).

In serious mental illness, sedating antidepressants can be considered when insomnia and anxious distress are prominent, but trimipramine requires careful balancing against anticholinergic and orthostatic harms, especially in older adults and polypharmacy (clinical).

Therapeutic drug monitoring (TDM) is commonly used with TCAs. AGNP guideline therapeutic reference range for trimipramine is 150–300 ng/mL (Hiemke 2018).

The compare view, trimipramine evidence feed, and trimipramine print page support documentation of why a sedating TCA was selected and how safety monitoring is planned.

Trimipramine is used less frequently than SSRIs/SNRIs because of anticholinergic burden, falls risk, and overdose lethality. When it is selected, follow-up focuses on sedation/functional safety, bowel and bladder symptoms, and ECG/TDM planning to avoid preventable toxicity.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

As a TCA, trimipramine has mixed monoamine effects and antagonizes H1, muscarinic, and α1-adrenergic receptors, which contribute to sedation, constipation/urinary retention, and Orthostatic hypotension (mechanism/class).

Sodium-channel blockade is a class effect that contributes to QRS widening and ventricular arrhythmia risk in overdose (class warning).

• Mixed monoamine effects with prominent H1/M1/α1 antagonism (sedation, anticholinergic effects, orthostasis).

Metabolism and Pharmacokinetics

• Metabolized hepatically; CYP2D6 and CYP3A4 variability and drug interactions can alter exposure (class/clinical).
• AGNP guideline elimination half-life is ~23–24 hours; an active metabolite (N-desmethyltrimipramine) contributes to exposure (Hiemke 2018).
• Because TCAs distribute widely and bind proteins, clinical observation is prioritized over early serum levels in suspected overdose (clinical).

Dosing and Administration

• Label dosing is individualized. Outpatient titration often starts at lower total daily doses (commonly 75 mg/day) and increases toward 150 mg/day as tolerated; labeling cautions against higher outpatient dosing (label).
• Hospitalized or closely monitored patients may require higher total daily doses, with careful attention to ECG changes, orthostasis, and anticholinergic burden (label/clinical).
• Older adults and medically frail patients typically start lower and titrate more slowly due to sedation, falls risk, and confusion (label/clinical).
• TDM: the AGNP therapeutic reference range is 150–300 ng/mL. Levels are commonly obtained after steady state or when response/toxicity is unclear in the setting of interactions (Hiemke 2018/clinical).
• When discontinuing after longer courses, gradual tapering is commonly used to reduce cholinergic rebound and to distinguish withdrawal from relapse (clinical).

Monitoring & Labs

• Baseline and follow-up ECG planning in patients with cardiac history, older age, electrolyte disturbance risk, or multiple QT-active drugs (clinical).
• TDM after steady state or after major interaction changes when response is partial or toxicity is suspected (Hiemke 2018/clinical).
• Orthostatic vitals, falls risk, and anticholinergic burden (bowel and bladder symptoms, cognition), especially in older adults (clinical).
• Suicidality and mood switching surveillance early in treatment and after dose changes, particularly in young adults and bipolar-spectrum illness (label/clinical).

Monitoring for a sedating TCA focuses on safety (falls risk, anticholinergic burden, ECG changes) while ensuring adequate exposure when response is incomplete (TDM).

Adverse Effects

Interactions

• MAOIs are contraindicated; washout periods are used to reduce risk of serotonin syndrome and hypertensive reactions (label).
• Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) can raise TCA exposure; dose adjustment and/or TDM are common mitigation strategies (clinical).
• Additive sedation and respiratory risk can occur with alcohol, benzodiazepines, opioids, and sedating antipsychotics (clinical).
• Other anticholinergic medications (some antipsychotics, antihistamines) can compound constipation, urinary retention, and delirium risk (clinical).
• QT- and conduction-active drugs increase cumulative arrhythmia risk; medication reconciliation typically includes OTC cold/sleep products (clinical).

Other Useful Information

• If sedation is a major target symptom (insomnia comorbidity), clinicians often compare alternatives with clearer evidence and lower anticholinergic burden before escalating TCA doses (clinical).
• When depressive symptoms occur in bipolar disorder, antidepressants are commonly paired with a mood stabilizer and monitored for mood switching; see the bipolar disorder hub for longitudinal care pathways.
• For older adults, medication review that reduces additive anticholinergic and sedative burden is often higher yield than adding multiple “side-effect” medications (clinical).

References

1. Trimipramine maleate capsules prescribing information — DailyMed (2025)
2. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 — Pharmacopsychiatry (2018)
3. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
4. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)