Schedule H

Oral

• Tablets: 10 mg, 25 mg

• Capsules: 10 mg, 25 mg, 50 mg (availability may vary by brand)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder

Parameter Details

Starting dose 25 mg once daily at bedtime

Titration Increase by 25 mg every 2–3 days based on response and tolerability

Usual maintenance dose 75–100 mg/day (single bedtime dose or divided doses)

Maximum dose 150 mg/day (specialist supervision required)

Clinical Notes:

• Onset of antidepressant effect typically takes 2–4 weeks

• Bedtime dosing preferred due to sedative effect

• Consider ECG before initiation in patients >40 years or with cardiac history

• Lower starting dose (10 mg) in elderly patients

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 based on response and tolerability

Usual maintenance dose 25–75 mg once daily at bedtime

Maximum dose 100 mg/day (rarely required)

Clinical Notes:

• Analgesic effect often occurs at lower doses than antidepressant doses

• Sedation may benefit patients with sleep disturbance due to nocturnal pain

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

• Start at lower end of dose range in elderly

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Notes

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

Tension-type Headache Prophylaxis 10–50 mg at bedtime Long-term OFF-LABEL; Specialist only; Evidence: Indian neurology practice

Chronic Pain Syndromes 10–75 mg at bedtime As needed OFF-LABEL; Specialist only (Pain specialist); Evidence: Pain clinic practice

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 20–35 mg at bedtime 50 mg/day

Clinical Notes:

• Use only when non-pharmacological measures have failed

• Administer 1–2 hours before bedtime

• Short-term use preferred (maximum 3 months per trial)

• Institute drug-free intervals to reassess need

Safety Monitoring:

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

• Monitor for sedation, mood changes, anticholinergic effects

• Assess for behavioural changes and suicidal ideation

• 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; Maximum: 50 mg/day OFF-LABEL; Specialist only (Child Psychiatrist); SSRIs preferred first-line; increased cardiovascular risk in children

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

Mild to moderate impairment No dose adjustment required

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

• Hypersensitivity to nortriptyline or other tricyclic antidepressants

• Recent myocardial infarction (within 6 weeks)

• Acute recovery phase post-myocardial infarction

• Severe cardiac arrhythmias (bundle branch block, heart block)

• Known prolonged QT syndrome

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

• Acute porphyria

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

• History of seizures or epilepsy — lowers seizure threshold

• Bipolar disorder — risk of precipitating manic episode

• Urinary retention or prostatic hypertrophy

• Angle-closure glaucoma (treated/controlled)

• Elderly patients — higher risk of anticholinergic and cognitive effects

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

• Hyperthyroidism or patients receiving thyroid medication

• Chronic constipation or paralytic ileus risk

• Abrupt withdrawal — may cause cholinergic rebound symptoms; taper gradually

Aspect Details

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

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

When it may be used Only if potential benefit justifies risk; avoid in first trimester if possible; specialist psychiatric input recommended

Monitoring required Fetal growth monitoring; neonatal adaptation syndrome (irritability, feeding difficulties, respiratory distress) if used in third trimester

Aspect Details

Compatibility Compatible with breastfeeding; nortriptyline is preferred TCA in lactation

Expected levels in milk Low (infant exposure minimal)

Preferred alternatives Sertraline (if SSRI preferred); nortriptyline itself is acceptable among TCAs

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 75–100 mg/day

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

Pre-initiation Baseline ECG recommended; assess fall risk and anticholinergic burden

Monitoring Blood pressure (lying and standing), mental status, ECG periodically

Key Point: Nortriptyline has lower anticholinergic burden compared to amitriptyline, making it a preferred TCA option in elderly when TCA use is necessary.

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 nortriptyline levels Avoid combination if possible; if essential, reduce nortriptyline dose significantly and monitor for toxicity

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

Clonidine Antagonism of antihypertensive effect; hypertensive rebound on clonidine withdrawal Avoid combination

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

Alcohol Enhanced CNS depression Advise strict avoidance

Interacting Drug Effect Recommendation

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

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

Valproate May increase TCA levels Monitor for toxicity

Rifampicin CYP induction; reduced nortriptyline efficacy Monitor response; consider alternative antidepressant

Oral contraceptives (oestrogen-containing) May elevate nortriptyline levels Monitor for adverse effects

Anticholinergics (oxybutynin, antihistamines) Additive anticholinergic effects Assess total anticholinergic burden; use with caution

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

Cimetidine CYP inhibition; increased nortriptyline levels Monitor for toxicity; consider alternative H2 blocker

Warfarin Potential for altered anticoagulant effect Monitor INR closely

• Dry mouth

• Constipation

• Drowsiness and sedation

• Dizziness

• Blurred vision

• Orthostatic hypotension

• Weight gain

• Increased sweating

• Tachycardia

• Urinary hesitancy

• 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

Agranulocytosis Rare; discontinue; monitor FBC

Hepatic dysfunction / Jaundice Discontinue; LFT monitoring

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, anticholinergic toxicity. 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, LFTs 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, mental status Every 3–6 months

Stable long-term therapy ECG Periodically in elderly or if on higher doses

If symptoms of toxicity Serum nortriptyline levels (therapeutic range: 50–150 ng/mL) As needed

Single-ingredient formulations:

• Nortimer (Intas)

• Primox (Sun Pharma)

• Sensival (RPG Life Sciences)

• Norpress (Mankind)

• Nortriptyline (Various generics)

Fixed-Dose Combinations:

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

Note: Nortriptyline is NOT included in NLEM 2022; not under NPPA price control. Available primarily in private sector.

1. Preferred TCA in elderly: Nortriptyline has lower anticholinergic burden and less sedation compared to amitriptyline, making it the preferred TCA choice when TCA therapy is necessary in elderly patients.

1. Preferred TCA in lactation: Among TCAs, nortriptyline has the lowest milk transfer and is considered the TCA of choice for breastfeeding mothers who require TCA therapy.

1. Therapeutic drug monitoring: Unlike most antidepressants, nortriptyline has an established therapeutic range (50–150 ng/mL). Serum level monitoring can guide dosing, especially in non-responders or suspected toxicity.

1. CYP2D6 interactions: Nortriptyline is primarily metabolised by CYP2D6. Co-administration with CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) can significantly increase levels — reduce nortriptyline dose by 50% or avoid combination.

1. Overdose lethality: Like all TCAs, nortriptyline has narrow therapeutic index. Dispense limited quantities in patients at suicide risk; counsel family about safe storage.

1. Lower doses for pain: Analgesic effect typically occurs at 25–75 mg/day, lower than antidepressant doses. Start at 10 mg in pain indications and titrate slowly.

tricyclic antidepressant; TCA; depression; neuropathic pain; nocturnal enuresis; migraine prophylaxis; elderly-preferred-TCA; lactation-compatible; ECG-monitoring; CYP2D6-substrate

RxIndia v1.0 — 25 Jan 2025

• CDSCO Approved Product Database

• Indian Pharmacopoeia (latest edition)

• API Textbook of Medicine

• AIIMS/ICMR Neuropathy Management Guidelines

• Indian Psychiatric Society Treatment Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• IAP Drug Formulary (for paediatric dosing)

• WHO EML (supportive reference for paediatric enuresis)