Schedule H

Oral

Formulation Strength

Tablets 25 mg, 75 mg

Capsules 25 mg

Note: Injectable formulation NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD)

Parameter Recommendation

Starting dose 75 mg/day in divided doses (25 mg TID) OR as single dose at night

Titration Increase by 25–50 mg every 1–2 weeks based on response and tolerability

Usual maintenance dose 75–150 mg/day

Maximum dose 225 mg/day (specialist supervision recommended above 150 mg)

Clinical Notes:

• Strong sedative properties — preferably administer as single night-time dose

• Particularly suitable for agitated depression or depression with prominent insomnia

• Therapeutic effect typically observed after 2–4 weeks

• Continue treatment for minimum 6–9 months after remission

1. Anxiety with Comorbid Depression

Parameter Recommendation

Starting dose 25–50 mg orally at bedtime

Titration Increase by 25 mg every 3–7 days based on tolerability

Usual maintenance dose 75–125 mg/day

Maximum dose 150 mg/day

Clinical Notes:

• Useful when anxiety, insomnia, and depressive symptoms coexist

• Sedating profile advantageous in anxious patients with sleep disturbance

• Monitor for excessive daytime sedation

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

Indication Dose Duration Notes Evidence

Neuropathic pain Starting: 25 mg at night; Titrate to 75 mg as tolerated Reassess after 4–6 weeks OFF-LABEL; Specialist only Indian specialist practice; extrapolated from related TCAs

Chronic insomnia with depression 25–50 mg at bedtime Ongoing as per clinical need OFF-LABEL; Specialist only Indian psychiatric practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable.

Dothiepin is NOT RECOMMENDED for treatment of depression in children and adolescents under 18 years due to increased risk of suicidal ideation and limited efficacy data.

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

Nocturnal Enuresis — Children ≥7 years

OFF-LABEL; Child Psychiatrist Supervision Mandatory

Parameter Recommendation

Starting dose 0.5–1 mg/kg at bedtime (not exceeding 25 mg)

Titration Not applicable for this indication

Usual maintenance dose 25 mg at bedtime

Maximum dose 25 mg/day

Duration Short-term only (≤3 months); reassess monthly

Safety Statement:

• Not recommended below 7 years

• ECG monitoring required if dose exceeds 25 mg/day or for prolonged use

• Use only when behavioural interventions and desmopressin have failed

• Monitor for anticholinergic effects and cardiac symptoms

Evidence: Extrapolated from use of related TCAs (imipramine) in enuresis; limited direct evidence for dothiepin

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

End-stage renal disease / Dialysis Avoid unless psychiatrist deems benefit outweighs risk; not significantly dialyzable

• Known hypersensitivity to dothiepin or any tricyclic antidepressant

• Recent myocardial infarction (within 3 months)

• Cardiac arrhythmias or significant conduction abnormalities (heart block, bundle branch block)

• Acute manic phase of bipolar disorder

• Severe hepatic impairment

• Concurrent use with MAO inhibitors (contraindicated within 14 days of MAO inhibitor discontinuation)

• Acute recovery phase following stroke

• History of seizures or epilepsy — lowers seizure threshold

• Urinary retention or prostatic hypertrophy — anticholinergic effects may worsen

• Narrow-angle glaucoma

• Elderly patients — increased sensitivity to anticholinergic and cardiovascular effects

• Bipolar disorder — risk of manic switch; use mood stabiliser if indicated

• Pre-existing QT prolongation or concurrent use of QT-prolonging agents

• History of suicidal ideation — close monitoring required, especially in first 4 weeks

• Cardiovascular disease (ischaemic heart disease, heart failure)

• Hyperthyroidism

• Concurrent electroconvulsive therapy (ECT)

Parameter Recommendation

Risk category Use only if potential benefit justifies risk; limited human data

Preferred alternatives SSRIs (sertraline preferred) if initiating antidepressant in pregnancy

When to use Only if SSRIs contraindicated/ineffective; specialist psychiatric input essential

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

Parameter Recommendation

Compatibility Not recommended; excretion in breast milk likely

Preferred alternatives Sertraline (lower milk transfer, better studied)

Drug levels in milk Low to moderate (limited data)

Infant monitoring Sedation, poor feeding, weight gain, irritability

Parameter Recommendation

Starting dose 25 mg once daily at night

Titration Slow — increase by 25 mg every 1–2 weeks; maximum usually 75–100 mg/day

Special risks Orthostatic hypotension (falls risk), excessive sedation, confusion, urinary retention, constipation, cardiac conduction abnormalities

Monitoring Orthostatic blood pressure, cognitive function, ECG, anticholinergic burden assessment

Precautions Avoid if history of ischaemic heart disease, arrhythmia, or recent falls; consider safer alternatives (SSRIs, mirtazapine)

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

Linezolid Serotonin syndrome risk MAO inhibition by linezolid Avoid combination

SSRIs (fluoxetine, paroxetine) Increased dothiepin levels; serotonin toxicity CYP2D6 inhibition Avoid or reduce dothiepin dose; monitor closely

Class 1A/III antiarrhythmics (quinidine, amiodarone, sotalol) QT prolongation, arrhythmias Additive cardiac effects Avoid combination

Other QT-prolonging drugs (haloperidol, ondansetron, fluoroquinolones) Torsades de pointes risk Additive QT prolongation Avoid or monitor ECG

CNS depressants (alcohol, benzodiazepines, opioids) Profound sedation, respiratory depression Additive CNS depression Avoid or use with extreme caution

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

Interacting Drug/Class Effect Management

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

Rifampicin Reduced dothiepin efficacy Consider alternative antidepressant or dose adjustment

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

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

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 and serotonin syndrome

Cimetidine Increased dothiepin levels CYP inhibition — consider dose reduction

• Sedation/drowsiness (very common)

• Dry mouth

• Constipation

• Blurred vision

• Dizziness

• Orthostatic hypotension

• Weight gain

• Urinary hesitancy/retention

• Tachycardia

• Sweating

• Sexual dysfunction

Most anticholinergic effects are dose-related and may improve with time

Adverse Effect Action Required

Seizures Discontinue; neurological evaluation; dose-related risk

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

QT prolongation / Torsades de pointes Discontinue; ECG; correct electrolytes

Suicidal ideation (especially in under-25s) Close monitoring first 4 weeks; specialist review; may need discontinuation

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

Neuroleptic malignant syndrome (rare) Discontinue; emergency management

Hepatotoxicity Discontinue; LFT monitoring; gastroenterology input

Agranulocytosis (rare) Discontinue; urgent haematology review

Hyponatraemia (SIADH) Monitor sodium; may need discontinuation

Note: TCA overdose is life-threatening — prescribe limited quantities in suicidal patients

Phase Parameters

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

After initiation / dose change Orthostatic blood pressure (first 2 weeks); mental status and suicidality assessment (weekly for first 4 weeks); ECG if dose exceeds 150 mg/day; response assessment at 4–6 weeks

Long-term Weight every 3 months; LFTs and renal function every 6–12 months; ECG annually if on high dose; periodic suicide risk assessment; taper planning after 6–9 months of remission

Brand Name Manufacturer Formulations

Prothiaden Abbott Tablets 25 mg, 75 mg

Dothep Wockhardt Tablets 25 mg, 75 mg; Capsules 25 mg

Dopress Micro Labs Tablets 25 mg, 75 mg

Dothwin Intas Tablets 25 mg

Notes:

• Not included in NLEM 2022

• Not under NPPA price control

• Moderate cost; widely available in private sector

• Limited government supply

1. Sedation as advantage: Strong sedative effect makes dothiepin suitable for anxious/agitated depression with insomnia — administer entire dose at bedtime

1. Not first-line: SSRIs preferred per Indian psychiatric practice guidelines; reserve dothiepin for cases requiring sedation or when SSRIs are contraindicated/ineffective

1. Overdose lethality: TCAs including dothiepin are dangerous in overdose (cardiotoxicity) — prescribe limited quantities (1–2 weeks supply) in patients with suicidal risk

1. ECG before high doses: Always obtain baseline ECG before exceeding 150 mg/day; avoid in patients with conduction abnormalities

1. Gradual tapering essential: Discontinue slowly over 4–6 weeks to prevent withdrawal symptoms (anxiety, insomnia, flu-like symptoms, movement disorders)

1. Anticholinergic burden: Assess total anticholinergic load in elderly patients — avoid combining with other anticholinergic drugs

dothiepin; dosulepin; tricyclic antidepressant; TCA; depression; anxiety; sedating antidepressant; QT prolongation; elderly caution; suicide risk; 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 Psychotropic Drug Use Guidelines

• Indian Psychiatric Society Clinical Practice Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO Essential Medicines List (supportive)

• Product Inserts: Prothiaden (Abbott), Dothep (Wockhardt)