Schedule H

Oral, Intramuscular

Formulation Strength

Tablets 10 mg, 25 mg, 75 mg

Modified-release tablets 75 mg (limited availability)

Injection 25 mg/mL (IM use; rarely used)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD)

Parameter Recommendation

Starting dose 25–50 mg/day in divided doses OR as single dose at night

Titration Increase by 25–50 mg every 3–4 days as tolerated

Usual maintenance dose 75–150 mg/day (in divided doses or once daily at bedtime)

Maximum dose 300 mg/day (specialist supervision mandatory for doses >150 mg)

Clinical Notes:

• Onset of clinical benefit typically requires 2–4 weeks

• Monitor closely for suicidal ideation during initial treatment phase

• Once-daily night-time dosing may improve adherence due to sedative effect

• Continue treatment for minimum 6–9 months after remission

1. Nocturnal Enuresis

(See Paediatric Dosing section for detailed dosing in children)

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

Indication Dose Duration Notes Evidence

Neuropathic pain Starting: 10–25 mg at bedtime; Titration: Increase by 10–25 mg weekly; Maintenance: 25–75 mg/day; Maximum: 150 mg/day Long-term; reassess at 4–6 weeks OFF-LABEL; Specialist only; Second-line after gabapentinoids or duloxetine Indian specialist pain management protocols; RCT evidence supportive

Panic disorder Starting: 10–25 mg/day; Titration: Increase by 10–25 mg every 3–5 days; Maintenance: 75–150 mg/day; Maximum: 200 mg/day Long-term with periodic reassessment OFF-LABEL; Specialist only; Slow titration to minimise jitteriness Indian psychiatry practice; extrapolated from RCTs

Cataplexy / Narcolepsy 50–150 mg/day at night Ongoing OFF-LABEL; Specialist only (neurologist/psychiatrist) Indian specialist use when modafinil/sodium oxybate unavailable

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Nocturnal Enuresis — Children ≥6 years

6–10 years 10–25 mg at bedtime If no response in 1–2 weeks, may increase gradually 50 mg/day

11–12 years 25 mg at bedtime If no response in 1–2 weeks, may increase gradually 75 mg/day

12 years 25 mg at bedtime If no response in 1–2 weeks, may increase 75 mg/day

Clinical Notes:

• Duration: Typically 3–12 weeks; avoid prolonged use

• Taper gradually when discontinuing (do not stop abruptly)

• Administer 1–2 hours before bedtime

• Behavioural interventions should be attempted first

Safety Monitoring:

• Baseline ECG recommended before initiation

• Monitor for mood changes, behavioural effects, cardiac symptoms

• Periodic reassessment of necessity for continued treatment

Secondary Indications — Paediatric Doses (Off-label, if any)

Indication Dose Duration Notes Evidence

Depression / Anxiety disorders Starting: 0.5–1 mg/kg/day in 1–2 divided doses; Maximum: 2.5 mg/kg/day OR 150 mg/day (whichever is lower) Variable; specialist-guided OFF-LABEL; Child psychiatrist supervision mandatory Limited evidence; reserved for severe, treatment-resistant cases; risk of behavioural effects and cardiac toxicity

Safety Statement:

• Not recommended below 6 years of age except under strict specialist psychiatric supervision

• Increased risk of suicidal ideation in children and adolescents — close monitoring essential

• ECG monitoring mandatory for doses exceeding weight-based recommendations or in prolonged use

• Black box warning applies for paediatric depression

Severe impairment (eGFR <30) Use with caution; limited data; consider dose reduction and plasma level monitoring

Haemodialysis Not significantly dialyzable; no supplemental dose required

• Known hypersensitivity to imipramine or other tricyclic antidepressants

• Acute recovery phase following myocardial infarction (within 6 weeks)

• Cardiac conduction abnormalities (bundle branch block, second/third-degree AV block)

• Concurrent use with MAO inhibitors OR within 14 days of discontinuing MAOIs

• Severe hepatic impairment

• Acute angle-closure glaucoma

• Acute urinary retention

• History of seizures or epilepsy — lowers seizure threshold

• Bipolar disorder — risk of precipitating manic episode

• Suicidal ideation — increased risk during early treatment, especially in adolescents and young adults

• Urinary retention or benign prostatic hyperplasia — anticholinergic effects may worsen

• Narrow-angle glaucoma (non-acute)

• Thyroid disease — amplified TCA toxicity with levothyroxine

• Cardiovascular disease (ischaemic heart disease, arrhythmias, heart failure)

• Elderly patients — high risk of orthostatic hypotension, confusion, falls

• Diabetes mellitus — may affect glycaemic control

• Avoid abrupt withdrawal after prolonged use — taper gradually

• Concurrent electroconvulsive therapy (ECT)

• Pheochromocytoma

Parameter Recommendation

Risk category Generally avoided; limited human data with some evidence of neonatal complications

Preferred alternatives SSRIs (sertraline preferred) in Indian obstetric practice

When to use Only if potential benefit clearly justifies risk; specialist psychiatric input essential

Monitoring Fetal growth (serial ultrasound); observe neonate for withdrawal symptoms (irritability, feeding difficulties, respiratory distress, seizures) in first week after delivery

Parameter Recommendation

Compatibility Use with caution; generally avoid if alternatives available

Preferred alternatives Sertraline, nortriptyline (better safety data during breastfeeding)

Drug levels in milk Low (imipramine and metabolite desipramine detected in low amounts)

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

Parameter Recommendation

Starting dose 10–25 mg/day (lower than standard adult dose)

Titration Very slow — increase by 10–25 mg every 5–7 days

Usual maintenance dose 50–100 mg/day (often lower than younger adults)

Maximum dose 100 mg/day (rarely higher without specialist input)

Special risks Orthostatic hypotension (falls risk), confusion, delirium, anticholinergic toxicity (constipation, urinary retention, cognitive impairment), cardiac conduction abnormalities

Monitoring Baseline and periodic ECG; postural blood pressure; cognitive assessment

Alternatives to consider Nortriptyline (less anticholinergic), SSRIs (better tolerated)

Interacting Drug/Class Effect Mechanism Management

MAO inhibitors (phenelzine, tranylcypromine, moclobemide) Hypertensive crisis, serotonin syndrome, hyperthermia Combined serotonergic and adrenergic potentiation Contraindicated — allow 14-day washout period

Linezolid Serotonin syndrome risk MAO inhibition Avoid combination

SSRIs (fluoxetine, paroxetine) Markedly increased imipramine levels; toxicity risk CYP2D6 inhibition Avoid or significantly reduce imipramine dose; monitor closely

Class IA/III antiarrhythmics (quinidine, amiodarone, sotalol) QT prolongation, additive cardiotoxicity Additive effects on cardiac conduction Avoid combination

Pimozide, cisapride, terfenadine Torsades de pointes QT prolongation Contraindicated

Clonidine Antagonism of antihypertensive effect; hypertensive crisis on clonidine withdrawal Pharmacodynamic antagonism Avoid combination; if used, monitor BP closely

Alcohol Enhanced CNS depression Additive effect Advise avoidance

Sympathomimetics (adrenaline, noradrenaline) Hypertensive crisis, arrhythmias Potentiation of catecholamine effects Avoid direct-acting sympathomimetics

Interacting Drug/Class Effect Management

Anticholinergic drugs (antihistamines, atropine, oxybutynin) Additive anticholinergic effects — constipation, urinary retention, dry mouth, confusion Monitor; avoid polypharmacy with multiple anticholinergics

Antipsychotics (haloperidol, risperidone) Additive QT prolongation; increased plasma levels of both drugs Monitor ECG; consider dose reduction

Carbamazepine, phenytoin, phenobarbital Reduced imipramine levels CYP enzyme induction — may need imipramine dose increase; monitor efficacy

Rifampicin Reduced imipramine efficacy CYP induction — consider alternative antidepressant

Oral contraceptives Increased imipramine levels CYP inhibition — monitor for toxicity

Cimetidine Increased imipramine levels CYP inhibition — consider dose reduction

Warfarin Potential increased bleeding risk Monitor INR closely during initiation and dose changes

Tramadol Increased seizure risk; serotonergic toxicity Use with caution; monitor for seizures

Thyroid hormones (levothyroxine) Amplified TCA cardiac effects Monitor ECG; use with caution in hyperthyroid patients

• Dry mouth

• Constipation

• Blurred vision

• Urinary hesitancy/retention

• Drowsiness/sedation

• Weight gain

• Orthostatic hypotension

• Tachycardia/palpitations

• Sweating

• Sexual dysfunction (decreased libido, erectile dysfunction)

• Dizziness

• Tremor

Most anticholinergic effects are dose-related and may diminish with continued use

Adverse Effect Action Required

Cardiac arrhythmias (especially in overdose) Discontinue; ECG monitoring; cardiology input; hospitalisation for overdose — potentially fatal

Seizures Discontinue; neurological evaluation; dose-related risk

Suicidal ideation (especially in adolescents/young adults) Close monitoring; specialist review; may need discontinuation

Acute angle-closure glaucoma Discontinue; emergency ophthalmology referral

Hepatitis / Cholestatic jaundice Discontinue; LFT monitoring; gastroenterology input

Serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability) Discontinue immediately; supportive care; hospitalisation

Agranulocytosis (rare) Discontinue; urgent haematology review

Hyponatraemia (SIADH) Monitor sodium; may need discontinuation

Neuroleptic malignant syndrome (rare) Discontinue; emergency management

Critical Warning: TCA overdose is life-threatening — prescribe limited quantities in suicidal patients; cardiac monitoring essential in overdose

Phase Parameters

Baseline ECG (mandatory in patients >40 years or with cardiac risk factors); LFTs; renal function; electrolytes; blood pressure (supine and standing); mental health assessment including suicide risk; weight

After initiation / dose change Blood pressure and heart rate (weekly for first 4 weeks); ECG if pre-existing cardiac disease or dose >150 mg; mental status and suicidality assessment (weekly for first 4 weeks, especially in young adults)

Long-term Weight every 3 months; LFTs annually; ECG annually in elderly or high-risk patients; periodic psychiatric reassessment; metabolic panel if prolonged use

Depsonil Abbott Tablets 10 mg, 25 mg, 75 mg

Tofranil (Legacy brand) Limited availability

Impranil Generic Tablets 25 mg

Imizine Generic Tablets 25 mg

Antidep Generic Tablets 25 mg, 75 mg

Note: Injection form (25 mg/mL) available under limited brands; used rarely in hospital settings

Notes:

• Not included in NLEM 2022

• Not under NPPA price control

• Affordable in generic form; widely available in private sector

• Available in government hospital supply in many states

1. ECG is essential: Obtain baseline ECG in all adults >40 years or with any cardiac risk factor before initiating therapy; repeat if dose exceeds 150 mg/day

1. Overdose lethality: TCAs including imipramine are highly dangerous in overdose (cardiotoxicity, seizures) — prescribe limited quantities (1–2 weeks supply) in patients with suicide risk; consider safer alternatives in high-risk patients

1. Nortriptyline as alternative: In elderly or patients intolerant to anticholinergic effects, consider nortriptyline — similar efficacy with better tolerability and less orthostatic hypotension

1. Slow titration reduces side effects: Gradual dose escalation (over 2–4 weeks) minimises anticholinergic effects, orthostatic hypotension, and improves compliance

1. Gradual tapering mandatory: Never stop abruptly after prolonged use — taper over 4–6 weeks to prevent withdrawal symptoms (nausea, headache, malaise, sleep disturbance)

1. Not first-line for depression: Rarely used as first-line for depression in current Indian practice; SSRIs preferred; imipramine reserved for treatment-resistant cases, neuropathic pain, or enuresis

imipramine; tricyclic antidepressant; TCA; depression; nocturnal enuresis; neuropathic pain; panic disorder; QT prolongation; anticholinergic; suicide risk; elderly caution; paediatric enuresis; Schedule H; psychiatry

RxIndia v1.0 — 10 Jun 2025

• CDSCO (Central Drugs Standard Control Organisation)

• Indian Pharmacopoeia / National Formulary of India (IP/NFI)

• NLEM 2022 (for exclusion note)

• API Textbook of Medicine

• AIIMS Psychiatry Formulary

• Indian Psychiatric Society Clinical Practice Guidelines

• IAP Guidelines (for paediatric enuresis)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Product Inserts: Depsonil (Abbott)