Schedule H

Oral

Form Strengths

Tablets 25 mg, 50 mg, 75 mg

Note: Injectable formulations are NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD) — Adults

(Including endogenous, reactive, and masked depression)

Parameter Dosing

Starting dose 25 mg once daily at bedtime OR 25 mg 2–3 times daily

Titration Increase by 25 mg every 3–5 days based on response and tolerability

Usual maintenance dose 75–150 mg/day (preferably as single bedtime dose or in divided doses)

Maximum dose 150 mg/day in outpatients; 225 mg/day under specialist supervision (inpatient setting)

Clinical Notes:

• Bedtime dosing preferred due to sedative properties

• Slow dose escalation minimises seizure risk

• Therapeutic response typically observed after 2–3 weeks

• Avoid doses exceeding 150 mg/day in outpatient settings due to increased seizure risk

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Anxiety with depressive features — OFF-LABEL 25–75 mg/day in divided doses or at bedtime Short-term (6–12 weeks); reassess for continuation Specialist only; Limited observational data; not first-line therapy

Dysthymia refractory to SSRIs — OFF-LABEL 50–100 mg/day 6–12 months depending on response Specialist only; Supported by select Indian psychiatric practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable — No approved paediatric indications in India

Secondary Indications — Paediatric (Off-label)

Indication Age Dose Notes

Depression (when SSRIs ineffective) — OFF-LABEL >12 years Starting: 0.5–1 mg/kg/day in divided doses; Titrate slowly; Max: 75–100 mg/day Specialist psychiatrist supervision mandatory; High seizure risk

Safety Monitoring:

• Baseline ECG mandatory

• Suicidal ideation screening before and during treatment

• Monitor weight, CNS symptoms, cardiac parameters

• Regular assessment for seizure activity

⚠️ Not recommended in children below 12 years except under strict specialist psychiatric and cardiologic supervision due to seizure risk and lack of safety data

Mild to moderate impairment No major dose adjustment required

Dialysis-dependent patients Avoid unless under specialist supervision; monitor closely

• Known hypersensitivity to maprotiline or other tetracyclic antidepressants

• History of seizure disorder or epilepsy

• Recent myocardial infarction (within 3 months)

• Acute recovery phase following MI

• Narrow-angle glaucoma

• Concurrent use with MAO inhibitors

• Use within 14 days of MAOI discontinuation

• Severe cardiac conduction abnormalities (bundle branch block, AV block)

• Lowered seizure threshold (including history of febrile seizures, head injury, alcohol withdrawal)

• Pre-existing cardiac disease or arrhythmias

• Urinary retention or prostatic hypertrophy

• Suicidal ideation (especially early in treatment phase)

• Elderly or debilitated patients

• Bipolar disorder (risk of manic switch)

• Hepatic or renal dysfunction

• Hyperthyroidism

• History of increased intraocular pressure

• Concurrent electroconvulsive therapy (ECT)

• Abrupt discontinuation (taper gradually)

Aspect Recommendation

Overall safety Limited human data; animal studies show potential risk; use only if benefits clearly outweigh risks

Preferred alternatives SSRIs (sertraline preferred) for mild-moderate depression under specialist guidance

When to use Only when other safer options have failed; requires specialist psychiatric input

Monitoring Fetal movements, growth scans; observe neonate for withdrawal symptoms, respiratory depression, feeding difficulties

Aspect Recommendation

Compatibility Not recommended; excreted in breast milk in clinically relevant amounts

Milk levels Moderate

Preferred alternatives Sertraline, nortriptyline (lower milk transfer)

Infant monitoring If unavoidable: observe for sedation, poor feeding, irritability, developmental milestones

Aspect Recommendation

Starting dose 25 mg once daily at bedtime

Titration Very slow; increase every 1–2 weeks in 25 mg increments

Usual maximum 75 mg/day (lower than standard adult dose)

Key risks Orthostatic hypotension, falls, cognitive impairment, confusion, urinary retention, constipation, cardiac arrhythmias

Monitoring ECG at baseline and periodically; serum sodium; postural blood pressure; cognitive function

Interacting Drug/Class Effect Recommendation

MAO inhibitors (phenelzine, tranylcypromine, moclobemide) Hypertensive crisis, serotonin syndrome Contraindicated; 14-day washout required

SSRIs (fluoxetine, paroxetine) CYP2D6 inhibition increases maprotiline levels; serotonin syndrome risk Avoid combination; if essential, use very low doses with close monitoring

Antiepileptics (phenytoin, carbamazepine) Additive seizure threshold lowering; altered metabolism Avoid if possible; monitor seizure control closely

Antiarrhythmics (quinidine, amiodarone, sotalol) Additive QT prolongation; cardiac arrhythmia risk Avoid combination

Clozapine Markedly increased seizure risk Avoid combination

Alcohol Additive CNS depression Avoid concurrent use

Interacting Drug/Class Effect Recommendation

Antihypertensives (clonidine, guanethidine) Blunted antihypertensive effect Monitor blood pressure; may need dose adjustment

Anticholinergics (antihistamines, antiparkinsonian drugs) Enhanced anticholinergic effects Monitor for urinary retention, constipation, confusion

Rifampicin Reduced maprotiline levels via CYP induction Monitor efficacy; may need dose increase

Warfarin Altered INR Monitor coagulation closely

Benzodiazepines Additive sedation Use lower doses; caution with activities requiring alertness

Sympathomimetics (adrenaline, noradrenaline) Enhanced pressor effect Use with caution; monitor blood pressure

Cimetidine Increased maprotiline levels Monitor for toxicity

• Drowsiness, sedation

• Dry mouth

• Dizziness, lightheadedness

• Constipation

• Weight gain

• Blurred vision

• Orthostatic hypotension

• Tremor

• Headache

• Fatigue

Adverse Effect Clinical Action

Seizures (dose-related, especially >150 mg/day) Discontinue immediately; supportive care; anticonvulsant if needed

Cardiac arrhythmias (tachycardia, conduction disturbances) Discontinue; ECG monitoring; cardiology consultation

Agranulocytosis (rare) Discontinue if unexplained fever, sore throat; urgent FBC

Hepatitis / Cholestatic jaundice Discontinue; monitor LFTs; supportive management

Suicidal ideation (especially in younger adults) Close monitoring; psychiatric evaluation; consider discontinuation

Neuroleptic malignant syndrome (rare) Discontinue immediately; supportive care; hospitalisation

Severe allergic reactions / Skin rash Discontinue; evaluate for hypersensitivity

Phase Parameters

Baseline ECG (especially in elderly, cardiac disease); FBC; LFTs; psychiatric assessment including suicidality; blood pressure

After initiation/dose changes Seizure activity (clinical observation); blood pressure; mental status; therapeutic response; signs of toxicity

Long-term ECG annually or with high doses; LFTs every 3–6 months; weight monitoring; periodic psychiatric reassessment

Brand Name Manufacturer

Ludiomil Novartis (limited availability)

Maprotil Various

Psymol Various

Note: Availability may vary by region; some brands intermittently discontinued

• NLEM status: Not included in NLEM

• Prices may vary widely by brand and region

1. Seizure threshold: Maprotiline has higher seizure risk than most antidepressants — keep dose ≤150 mg/day in outpatients and titrate slowly

1. Sedation advantage: More sedating than SSRIs, which may benefit patients with depression accompanied by insomnia or agitation

1. Onset of action: Allow 2–3 weeks before assessing efficacy; premature dose escalation increases adverse effects without improving response

1. Not first-line: Reserve for patients who have failed or cannot tolerate SSRIs/SNRIs due to unfavourable side effect profile and seizure risk

1. Withdrawal: Avoid abrupt discontinuation after prolonged use — taper gradually over 2–4 weeks to prevent withdrawal symptoms

1. Sexual dysfunction: Less sexual dysfunction compared to SSRIs, but more weight gain and anticholinergic effects

maprotiline; depression; tetracyclic antidepressant; TeCA; seizure-risk; sedating; Schedule H; elderly-caution; non-NLEM; psychiatry; anticholinergic

RxIndia v1.0 — 10 Jan 2025

• CDSCO Approved Formulations List

• Indian Pharmacopoeia

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Psychiatry Drug Formulary

• Indian Psychiatric Society Clinical Practice Documents

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Select RCT/meta-analyses (off-label indications only — clearly marked)