Schedule H

Oral

• Tablets: 25 mg, 50 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD)

Parameter Recommendation

Starting dose 50–75 mg/day (single bedtime dose or divided doses)

Titration Increase by 25 mg every 3–4 days based on tolerance

Usual maintenance dose 100–150 mg/day in 1–3 divided doses

Maximum dose 200 mg/day (outpatient); up to 300 mg/day (inpatient, specialist care)

Clinical notes:

• Pronounced sedative effect — bedtime dosing preferred

• Allow 2–4 weeks for therapeutic response assessment

• Gradual tapering required when discontinuing

Secondary Indications – Adults Only (Off-label, if any)

1. Generalised Anxiety Disorder (GAD) — OFF-LABEL

• Dose: Start 25 mg at bedtime; titrate to 75–150 mg/day

• Duration: Minimum 4–6 weeks trial

• Specialist only

• Evidence: Limited clinical studies; considered when SSRIs contraindicated or ineffective

1. Severe Insomnia (comorbid with depression) — OFF-LABEL

• Dose: 25–50 mg at bedtime

• Duration: Short-term use preferred

• Specialist only

• Evidence: Indian specialist practice; useful when SSRI-induced activation problematic

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — No approved paediatric indications for trimipramine in India.

Secondary Indications – Paediatrics (Off-label, if any)

Nocturnal Enuresis — OFF-LABEL

6–10 years 25 mg at bedtime May increase to 50 mg/day after 1 week 75 mg/day

10–16 years 25–50 mg at bedtime May increase to 75 mg/day after 1 week 100 mg/day

• Duration: Limit to ≤3 months with periodic drug-free intervals

• Specialist only

• Evidence: Established use based on TCA class evidence; imipramine better studied

Safety monitoring:

• Baseline ECG mandatory before initiation

• Monitor for CNS effects and suicidal ideation

• Rule out organic causes before initiation

Age restriction: Not recommended below 6 years except under exceptional specialist supervision.

Note: Not recommended for depressive or anxiety disorders in children due to unfavourable risk-benefit profile and insufficient evidence.

• Mild-to-moderate impairment: No dosage adjustment required

• Severe impairment/ESRD: Use with caution; limited data available

• Dialysis: Not significantly removed by haemodialysis or peritoneal dialysis

• Hypersensitivity to trimipramine or other tricyclic antidepressants

• Recent myocardial infarction (within 3 months)

• Concomitant use with MAO inhibitors or within 14 days of MAOI discontinuation

• Severe hepatic impairment

• Untreated narrow-angle glaucoma

• Acute urinary retention

• Severe prostatic hypertrophy with urinary obstruction

• Acute alcohol intoxication

• Bundle branch block or other cardiac conduction defects

• History of seizures or epilepsy

• Pre-existing cardiac arrhythmias or conduction abnormalities

• Bipolar disorder (risk of manic switch)

• Diabetes mellitus (may alter glycaemic control)

• Concurrent use of CNS depressants

• Elderly patients (increased sensitivity to anticholinergic and cardiovascular effects)

• History of suicidal ideation or behaviour

• Hyperthyroidism or patients receiving thyroid medication

• Phaeochromocytoma

• Avoid abrupt discontinuation (withdrawal symptoms may occur)

Parameter Recommendation

Risk category Limited human data; potential risk cannot be excluded

Preferred alternatives Sertraline generally preferred in Indian obstetric practice

When may be used Only in severe refractory depression when SSRIs ineffective; psychiatric supervision mandatory

Monitoring Fetal growth monitoring; observe neonate for withdrawal symptoms and sedation if used in third trimester

Parameter Recommendation

Compatibility Not recommended during breastfeeding

Preferred alternatives Sertraline or nortriptyline (lower milk levels, better safety data)

Levels in milk Low to moderate

Infant monitoring Monitor for sedation, poor feeding, irritability, and inadequate weight gain

• Starting dose: 25 mg/day at bedtime

• Titration: Slow — increase every 1–2 weeks based on tolerance

• Maximum dose: Generally limit to 100 mg/day

• Extra risks:

• Orthostatic hypotension and falls

• Confusion and cognitive impairment

• Cardiac conduction delays

• Urinary retention

• Constipation (may progress to ileus)

• Note: High anticholinergic burden — consider safer alternatives (SSRIs, mirtazapine) when possible

Interacting Drug Effect/Risk Management

MAO inhibitors Serotonin syndrome, hypertensive crisis Contraindicated; 14-day washout required

SSRIs (fluoxetine, paroxetine) CYP2D6 inhibition increases TCA levels — risk of toxicity Avoid combination or reduce TCA dose by 50%; monitor ECG

Class 1C antiarrhythmics (flecainide, propafenone) Additive cardiac conduction abnormalities Avoid combination

QT-prolonging drugs (cisapride, macrolides, antipsychotics) Increased risk of torsades de pointes Avoid combination

Alcohol Potentiates CNS depression; overdose risk Strongly counsel avoidance

Sympathomimetics (adrenaline, noradrenaline) Exaggerated pressor response Use with extreme caution

Interacting Drug Effect/Risk Management

Carbamazepine Enzyme induction reduces TCA levels Monitor clinical response; may need dose increase

Phenytoin Enzyme induction reduces TCA levels Monitor clinical response

Rifampicin Reduces serum trimipramine levels Monitor for reduced efficacy

Oral contraceptives May increase TCA levels via CYP inhibition Monitor for adverse effects

Clonidine, guanethidine Reduced antihypertensive efficacy Avoid combination if possible

Anticholinergics (oxybutynin, trihexyphenidyl) Additive anticholinergic effects Monitor for toxicity; minimise combined use

Cimetidine Inhibits TCA metabolism Monitor for increased side effects

• Dry mouth

• Constipation

• Sedation and drowsiness

• Dizziness

• Blurred vision

• Weight gain

• Orthostatic hypotension

• Urinary hesitancy

• Increased appetite

• Fatigue

• Cardiac arrhythmias (QT prolongation, heart block, ventricular arrhythmias)

• Seizures (lowered seizure threshold)

• Mania or hypomania induction

• Suicidal ideation (especially in younger patients — black box warning consideration)

• Anticholinergic delirium and hallucinations

• Paralytic ileus

• Agranulocytosis (rare)

• Hepatotoxicity (rare)

• Hyponatraemia/SIADH (rare)

Phase Parameters

Baseline ECG (especially elderly/CV risk), liver function, renal function, blood pressure, suicide risk assessment, weight

After initiation Mood symptoms weekly for first 4 weeks; blood pressure (orthostatic); sedation; ECG if high-risk patient

Long-term Weight and BMI; blood glucose (diabetics); periodic ECG if dose >150 mg/day; mood and suicidality assessment

Limited availability in India. Verify current market availability before prescribing.

Common brands reported:

• Trimontel®

Note: Trimipramine has limited market presence in India compared to other TCAs (amitriptyline, imipramine). Available as monotherapy only; no fixed-dose combinations.

• Not listed in NLEM 2022

• Not under DPCO price control

• Limited availability may affect pricing

• Strong sedative profile — particularly useful in depressed patients with prominent insomnia

• Unlike most TCAs, trimipramine has minimal REM sleep suppression — may preserve normal sleep architecture

• Less norepinephrine reuptake inhibition compared to other TCAs; primarily acts via histamine H1 and serotonin 5-HT2 receptor blockade

• Not first-line for depression in current Indian practice — SSRIs preferred per national guidelines

• High overdose toxicity — dispense limited quantities in patients with suicidal risk

• Anticholinergic burden significant though slightly less than amitriptyline — still requires caution in elderly

trimipramine; tricyclic; TCA; depression; insomnia; enuresis; sedation; elderly-caution; anticholinergic; psychiatry

RxIndia v0.3 — 13 Jan 2025

• CDSCO – Approved Products Database

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th edition

• Indian Psychiatric Society consensus guidelines

• AIIMS Pharmacology protocols

• NLEM 2022 (drug not included)

• Standard pharmacology references for off-label use evidence