Schedule H

Oral

• Tablets: 10 mg, 25 mg, 50 mg, 75 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder

Parameter Details

Starting dose 25–50 mg once daily at bedtime

Titration Increase by 25 mg every 5–7 days based on response and tolerability

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

Maximum dose 300 mg/day (inpatient supervision required for doses >150 mg/day)

Clinical Notes:

• Lower starting dose (10–25 mg) in elderly and medically frail patients

• Therapeutic response may take 2–4 weeks; adequate trial requires 6–8 weeks

• Bedtime dosing preferred due to sedative effect

• Consider ECG before initiating in patients >40 years or with cardiac risk factors

1. Neuropathic Pain (Diabetic Neuropathy, Post-herpetic Neuralgia)

Parameter Details

Starting dose 10–25 mg once daily at bedtime

Titration Increase by 10–25 mg every 3–7 days as tolerated

Usual maintenance dose 25–75 mg once daily at bedtime

Maximum dose 100 mg/day

Clinical Notes:

• Analgesic effect often occurs at lower doses than antidepressant effect

• Evaluate response after 3–4 weeks; minimum trial duration 6–8 weeks

• May be used in combination with gabapentinoids if inadequate response

1. Nocturnal Enuresis (Children ≥6 years)

See Paediatric Dosing section for details.

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Notes

Migraine Prophylaxis Starting: 10–25 mg at bedtime; Maintenance: 25–75 mg at bedtime Minimum 2–3 months trial OFF-LABEL; Specialist only (Neurologist); Evidence: International trials; consistent with Indian neurology practice

Fibromyalgia 10–50 mg once daily at bedtime Long-term OFF-LABEL; Specialist only (Rheumatologist/Pain specialist); Evidence: Multiple RCTs; used in Indian pain clinics

Tension-type Headache Prophylaxis 10–50 mg once daily at bedtime Minimum 2–3 months trial OFF-LABEL; Specialist only; Evidence: International guidelines and Indian neurology practice

Chronic Insomnia (with comorbid depression/pain) 10–25 mg at bedtime Short-term (<4 weeks); not first-line OFF-LABEL; Evidence: Indian geriatric psychiatry practice; safer alternatives preferred

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Nocturnal Enuresis (Children ≥6 years)

6–10 years 10 mg at bedtime 10–20 mg at bedtime 25 mg/day

11–16 years 10–25 mg at bedtime 25–50 mg at bedtime 50 mg/day

Clinical Notes:

• Use only when non-pharmacological measures have failed

• Administer 1–2 hours before bedtime

• Reassess need after 2–4 weeks; limit continuous use to 3 months per trial

• Institute drug-free intervals to assess continued need

Safety Monitoring:

• Baseline: ECG recommended if dose >25 mg/day or cardiac risk factors

• Monitor for sedation, mood changes, anticholinergic effects

• Warn caregivers about overdose toxicity risk — store safely

Secondary Indications – Paediatrics (Off-label)

Indication Dose Notes

Depression in adolescents (≥12 years) Starting: 10 mg/day; Maintenance: 25–50 mg/day; Maximum: 100 mg/day OFF-LABEL; Specialist only (Child Psychiatrist); SSRIs are preferred first-line; TCAs associated with increased cardiovascular risk in children

Age Restriction: NOT RECOMMENDED below 6 years of age except under child psychiatrist supervision. TCAs have higher toxicity risk in young children.

Note: Amitriptyline undergoes extensive hepatic metabolism; impaired clearance significantly increases toxicity risk.

• Recent myocardial infarction (within 6 weeks)

• Cardiac arrhythmias (especially bundle branch block, heart block)

• Acute recovery phase post-MI

• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation

• Known hypersensitivity to amitriptyline or other tricyclic antidepressants

• Severe hepatic impairment

• Acute porphyria

• Uncontrolled narrow-angle glaucoma

• Elderly patients — higher risk of falls, confusion, anticholinergic effects, orthostatic hypotension

• History of seizures or epilepsy — lowers seizure threshold

• Prostatic hypertrophy — risk of urinary retention

• Chronic constipation or paralytic ileus risk

• Angle-closure glaucoma (treated/controlled)

• Cardiovascular disease (ischaemic heart disease, heart failure, conduction abnormalities)

• History of suicidal ideation — may worsen early in treatment; close monitoring required

• Bipolar disorder — risk of precipitating manic episode

• Hyperthyroidism or patients receiving thyroid medication

• Diabetes mellitus — may alter glycaemic control

• Abrupt withdrawal — may cause cholinergic rebound symptoms (nausea, headache, malaise); taper gradually

Aspect Details

Overall safety Use with caution; limited human data; potential risk of neonatal withdrawal symptoms and cardiac effects

Preferred alternatives Sertraline, fluoxetine (SSRIs preferred in Indian obstetric practice)

When it may be used Only if potential benefit justifies risk; specialist psychiatric input recommended

Monitoring required Fetal cardiac monitoring if used in third trimester; monitor neonate for withdrawal symptoms (irritability, feeding difficulties, hypotonia)

Aspect Details

Compatibility Likely compatible; excreted in low levels in breast milk

Expected levels in milk Low

Preferred alternatives Sertraline, nortriptyline (lower milk transfer)

Infant monitoring Sedation, feeding difficulty, irritability, poor weight gain

Aspect Recommendation

Starting dose 10–25 mg once daily at bedtime

Titration Very gradual; increase every 1–2 weeks

Maximum dose Generally limit to 50–75 mg/day

Additional risks Orthostatic hypotension (falls, fractures), cognitive impairment/confusion, urinary retention, constipation, sedation, cardiac arrhythmias

Pre-initiation Baseline ECG recommended; assess fall risk

Monitoring Blood pressure (lying and standing), mental status, anticholinergic burden

Key Point: Amitriptyline is on the Beers Criteria list of potentially inappropriate medications in elderly due to high anticholinergic burden. Consider alternatives (e.g., nortriptyline, SSRIs, SNRIs) when possible.

Interacting Drug Effect Recommendation

MAOIs (phenelzine, tranylcypromine, moclobemide) Risk of serotonin syndrome, hypertensive crisis, hyperpyrexia Contraindicated — maintain 14-day washout between drugs

SSRIs (fluoxetine, paroxetine) CYP2D6 inhibition; markedly increased amitriptyline levels Avoid combination if possible; if essential, reduce amitriptyline dose significantly and monitor for toxicity

QT-prolonging drugs (haloperidol, thioridazine, erythromycin, fluoroquinolones, ondansetron) Additive QT prolongation; risk of torsades de pointes Avoid concurrent use; ECG monitoring essential if unavoidable

Sympathomimetics (adrenaline, noradrenaline) Enhanced pressor effect Avoid concurrent use

Alcohol Enhanced CNS depression Advise strict avoidance

Anticholinergic drugs (oxybutynin, benztropine, antihistamines) Additive anticholinergic toxicity (confusion, urinary retention, ileus, hyperthermia) Avoid combination; assess total anticholinergic burden

Interacting Drug Effect Recommendation

Carbamazepine CYP3A4 induction; decreased amitriptyline levels Monitor response; may need amitriptyline dose increase

Rifampicin CYP3A4 induction; significantly reduced amitriptyline efficacy Monitor therapeutic response; consider alternative antidepressant

Phenytoin Altered levels of both drugs Monitor phenytoin levels and amitriptyline response

Warfarin Potential for altered anticoagulant effect Monitor INR closely

Tramadol Increased seizure risk; potential serotonergic interaction Avoid if possible; use with caution

Cimetidine CYP inhibition; increased amitriptyline levels Monitor for toxicity; consider ranitidine/PPI as alternative

Methylphenidate May increase TCA levels Monitor for adverse effects

Clonidine Reduced antihypertensive effect Monitor blood pressure

Antihypertensives Enhanced hypotensive effect Monitor blood pressure; adjust doses as needed

• Dry mouth

• Constipation

• Drowsiness and sedation

• Blurred vision

• Dizziness

• Orthostatic hypotension

• Weight gain

• Increased appetite

• Urinary hesitancy

• Tachycardia

• Sweating

• Tremor

• Sexual dysfunction

Adverse Effect Action Required

Cardiac arrhythmias (especially in overdose) Discontinue immediately; ECG monitoring; cardiology referral

QT prolongation / Torsades de pointes Discontinue immediately; hospitalisation

Seizures Discontinue; supportive management

Severe orthostatic hypotension Dose reduction or discontinuation

Acute urinary retention Discontinue; catheterisation may be required

Paralytic ileus Discontinue; surgical evaluation

Agranulocytosis Rare; discontinue; monitor FBC

Hepatotoxicity Rare; discontinue; LFT monitoring

SIADH / Hyponatraemia Monitor sodium; discontinue if severe

Serotonin syndrome (with concurrent serotonergic drugs) Discontinue all serotonergic agents; supportive care

Suicidal ideation activation Close monitoring especially in first 2–4 weeks; specialist review

Mania/hypomania (in bipolar patients) Discontinue; mood stabiliser required

Overdose Warning: TCA overdose is life-threatening. Features include arrhythmias, seizures, hypotension, coma. ECG monitoring and sodium bicarbonate therapy may be required. ICU admission essential.

Phase Parameters Frequency

Baseline ECG (if age >40 years or cardiac risk factors), blood pressure, weight, mental status assessment Before initiation

During titration Blood pressure (lying/standing), mental status, side-effect assessment, suicidal ideation screening Weekly for first 4 weeks

Stable long-term therapy Weight, blood pressure Every 3–6 months

Stable long-term therapy ECG Annually if on doses >100 mg/day or elderly

Stable long-term therapy LFTs, FBC Periodically if on long-term high doses

If symptoms of toxicity Serum amitriptyline levels (if available) As needed

Single-ingredient formulations:

• Tryptomer (Wockhardt)

• Amitone (Intas)

• Amyline (Mankind)

• Eliwel (Sun Pharma)

• Sarotena (Lundbeck)

• Multiple generic brands available

Fixed-Dose Combinations:

• Amitriptyline + Perphenazine

Note: FDC use should be clinically justified; single-ingredient formulations preferred for dose titration.

Note: Amitriptyline is included in NLEM 2022 for depression and neuropathic pain indications; NPPA price-controlled formulations available. Widely available in government supply.

1. Not first-line for depression: Due to side-effect burden and lethality in overdose, TCAs are generally reserved for treatment-resistant depression or when SSRIs/SNRIs are ineffective or contraindicated.

1. Dual benefit in comorbidity: Amitriptyline is particularly useful in patients with comorbid depression and chronic pain conditions (neuropathic pain, fibromyalgia, chronic headaches) — one drug addresses both.

1. Lower doses for pain: Analgesic effect typically occurs at 25–75 mg/day, lower than antidepressant doses. Start low in pain indications.

1. Overdose lethality: TCAs have narrow therapeutic index. Avoid in actively suicidal patients. Dispense limited quantities; counsel family about safe storage.

1. Anticholinergic burden: Assess total anticholinergic burden when prescribing to elderly. Consider using the Anticholinergic Cognitive Burden (ACB) scale to minimize cumulative risk.

1. Gradual withdrawal: Do not stop abruptly after prolonged use — taper over 4–6 weeks to avoid withdrawal symptoms (nausea, headache, malaise, sleep disturbance).

tricyclic antidepressant; TCA; depression; neuropathic pain; nocturnal enuresis; migraine prophylaxis; NLEM India; elderly-caution; cardiac-risk; MAOI-contraindicated; overdose-lethal

RxIndia v1.0 — 25 Jan 2025

• CDSCO Approved Product Database

• Indian Pharmacopoeia (latest edition)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine (11th edition)

• AIIMS Psychopharmacology Handbook

• ICMR Guidelines for Neuropathic Pain Management

• Indian Psychiatric Society Treatment Guidelines

• Indian Pain Society Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• IAP Drug Formulary (for paediatric dosing)

• WHO EML (supportive reference)