Schedule H

Oral, Intramuscular

• Immediate-release tablets: 10 mg, 25 mg, 50 mg, 75 mg

• Sustained-release (SR) tablets: 75 mg

• Injection: 25 mg/2 mL ampoule (IM use)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Obsessive-Compulsive Disorder (OCD)

Clomipramine is considered the most effective TCA for OCD and remains an important option when SSRIs fail or are not tolerated.

Parameter Recommendation

Starting dose 25 mg once daily at bedtime

Titration Increase by 25 mg every 4–7 days based on tolerability

Usual maintenance dose 100–150 mg/day (given in divided doses or as single bedtime dose)

Maximum dose 250 mg/day (up to 300 mg/day in hospitalised patients under close supervision)

Clinical Notes:

• Onset of anti-obsessional effect typically 2–4 weeks; full response may take 8–12 weeks

• Doses above 150 mg/day should be given in divided doses to reduce peak plasma concentration-related adverse effects

• Continue for minimum 1–2 years after symptom control achieved

• SR formulation may improve tolerability and compliance

1. Major Depressive Disorder (MDD)

Parameter Recommendation

Starting dose 25 mg once daily at bedtime

Titration Increase by 25 mg every 4–7 days based on response and tolerability

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

Maximum dose 250 mg/day

Clinical Notes:

• Not first-line for depression in current practice; SSRIs/SNRIs preferred

• May be considered when other antidepressants have failed or in severe depression with prominent anxiety/insomnia

• ECG monitoring advisable in patients >40 years or with cardiovascular risk factors

• Therapeutic response typically within 2–4 weeks

1. Panic Disorder (with or without Agoraphobia)

Parameter Recommendation

Starting dose 10 mg once daily (very gradual initiation essential)

Titration Increase by 10–25 mg every 7–14 days as tolerated

Usual maintenance dose 75–150 mg/day

Maximum dose 250 mg/day

Clinical Notes:

• Start at lower dose than for depression to avoid initial panic exacerbation

• Very slow titration essential as patients with panic disorder are highly sensitive to medication side effects

• Full efficacy may take 6–8 weeks

1. Phobic Disorders

Parameter Recommendation

Starting dose 25 mg once daily

Titration Increase by 25 mg every 7 days

Usual maintenance dose 75–150 mg/day

Maximum dose 250 mg/day

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Chronic Neuropathic Pain Starting: 10–25 mg at bedtime; Maintenance: 25–75 mg/day; Maximum: 150 mg/day Evaluate response at 4–6 weeks; continue if effective OFF-LABEL — Specialist only. Based on extrapolation from amitriptyline data and Indian pain clinic practice. Lower doses often effective for analgesia than for psychiatric indications.

Cataplexy in Narcolepsy Starting: 10–25 mg/day; Maintenance: 25–75 mg/day; Maximum: 150 mg/day Long-term OFF-LABEL — Specialist only (Sleep Medicine/Neurology). Second-line when first-line agents unavailable. Based on limited RCT evidence.

Premature Ejaculation 25–50 mg/day OR 25 mg 4–6 hours before intercourse As needed or daily OFF-LABEL — Based on delay of ejaculation as pharmacological effect. Used in Indian andrology/sexology practice. SSRIs preferred by many specialists.

Trichotillomania Starting: 25 mg/day; Maintenance: 50–150 mg/day Long-term OFF-LABEL — Specialist only. Limited RCT evidence.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Obsessive-Compulsive Disorder (OCD)

Clomipramine is one of the most effective medications for paediatric OCD. Use under child psychiatrist supervision only.

Age-based Dosing (≥10 years):

Parameter Recommendation

Starting dose 10–25 mg once daily at bedtime (or 0.5 mg/kg/day)

Titration Increase by 10–25 mg every 4–7 days; or by 0.5 mg/kg increments

Usual maintenance dose 2–3 mg/kg/day OR 100–150 mg/day (whichever is lower)

Maximum dose 3 mg/kg/day OR 200 mg/day (whichever is lower); up to 250 mg/day in adolescents under close supervision

Clinical Notes:

• Divide total daily dose if exceeds 1 mg/kg or 50 mg (to reduce adverse effects)

• Response may take 8–12 weeks

• Continue for minimum 1 year after symptom control

• ECG recommended at baseline and after dose stabilisation

Minimum Age Statement: Not recommended in children below 10 years of age except under specialist child psychiatrist supervision in exceptional circumstances.

Safety Monitoring:

• ECG at baseline and periodically (QTc monitoring)

• Weekly assessment for suicidal ideation during first month, then monthly for 3 months

• Weight and height monitoring every 3 months

• Blood pressure and heart rate monitoring

• Liver function tests if prolonged use or symptomatic

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Nocturnal Enuresis ≥6 years 20–50 mg at bedtime (approximately 0.5–1 mg/kg); maximum 75 mg OFF-LABEL — Specialist only. Third-line after desmopressin and alarm therapy. Older Indian practice; limited current use. Risk of cardiotoxicity in accidental overdose. Short-term use only; taper to discontinue.

Depression in Adolescents ≥12 years Starting: 10–25 mg/day; Maintenance: 1–3 mg/kg/day; Maximum: 150–200 mg/day OFF-LABEL — Specialist only. Not first-line; SSRIs (fluoxetine) preferred. Enhanced suicidality monitoring mandatory.

• Recent myocardial infarction (within 3 months) or unstable angina

• Known cardiac arrhythmias, heart block (second/third degree), or prolonged QT interval

• Concurrent use with MAO inhibitors (including moclobemide, selegiline, linezolid) — minimum 14-day washout required before or after MAOI

• Acute recovery phase after myocardial infarction

• Known hypersensitivity to clomipramine, other tricyclic antidepressants, or any excipient

• Severe hepatic impairment

• Uncontrolled narrow-angle glaucoma

• Urinary retention due to prostatic hypertrophy or other causes

• Paralytic ileus

• History of seizure disorder or conditions lowering seizure threshold — clomipramine lowers seizure threshold in dose-dependent manner; risk increases significantly above 250 mg/day

• Suicidal ideation — enhanced risk during initial treatment period, especially in adolescents and young adults; close monitoring required

• Bipolar disorder — risk of precipitating manic/hypomanic episode; use with mood stabiliser

• Cardiovascular disease — may cause conduction abnormalities, orthostatic hypotension, tachycardia; ECG monitoring recommended

• Elderly patients — increased sensitivity to anticholinergic effects, orthostatic hypotension, falls risk

• Prostatic hypertrophy — risk of urinary retention (even without complete obstruction)

• Narrow-angle glaucoma (treated) — monitor intraocular pressure

• Hyperthyroidism or patients receiving thyroid medication — increased cardiovascular effects

• Concurrent ECT — may increase seizure duration

• Diabetes mellitus — may alter glycaemic control

• Concurrent serotonergic drugs — risk of serotonin syndrome

• Phaeochromocytoma — theoretical risk of hypertensive crisis

• Abrupt discontinuation — risk of withdrawal symptoms; always taper gradually

• Surgery — consider discontinuing several days before elective surgery (discuss with anaesthetist)

Parameter Recommendation

Safety Category Limited human data; animal studies show some evidence of teratogenicity; case reports of limb abnormalities (inconclusive); neonatal withdrawal syndrome and anticholinergic effects reported with third-trimester exposure

Preferred Alternatives SSRIs (sertraline, fluoxetine) are preferred first-line antidepressants during pregnancy in Indian obstetric psychiatry practice

When to Use May be considered in treatment-resistant OCD or depression when SSRIs have failed; requires careful risk-benefit assessment and joint obstetric-psychiatry decision

Monitoring Fetal anomaly screening; neonatal monitoring for withdrawal symptoms (irritability, feeding difficulties, respiratory distress, seizures) and anticholinergic effects (urinary retention, constipation) if third-trimester exposure

Parameter Recommendation

Breastfeeding Compatibility Generally not recommended; excreted in breast milk

Drug Levels in Milk Low to moderate; relative infant dose approximately 1–3%

Preferred Alternatives Sertraline and paroxetine have more safety data in breastfeeding; preferred if SSRI suitable for indication

Infant Monitoring If used: monitor for sedation, poor feeding, constipation, irritability, and developmental milestones; consider monitoring infant plasma levels if symptomatic

Parameter Recommendation

Starting dose 10 mg once daily at bedtime

Titration Slower titration at 7–14 day intervals; increase by 10–25 mg increments

Maximum dose 75–100 mg/day (lower than younger adults)

Additional Risks Orthostatic hypotension (falls risk); cognitive impairment and confusion; urinary retention; constipation and ileus; cardiac conduction abnormalities; SIADH/hyponatraemia; drug interactions due to polypharmacy

Monitoring Baseline ECG mandatory; lying and standing blood pressure; cognitive assessment; regular review of anticholinergic burden; serum sodium periodically

Note: SSRIs (sertraline, fluvoxamine) preferred over TCAs for OCD in elderly due to better safety profile.

Interacting Drug Mechanism/Effect Management

MAOIs (phenelzine, tranylcypromine, moclobemide, selegiline) Risk of severe serotonin syndrome, hypertensive crisis, hyperthermia, death Contraindicated; 14-day washout before or after MAOI

Linezolid, IV methylene blue MAOI activity; serotonin syndrome risk Avoid concurrent use

SSRIs (fluoxetine, paroxetine, fluvoxamine) CYP2D6/1A2 inhibition increasing clomipramine levels; additive serotonergic effect Avoid combination or reduce clomipramine dose by 50%; monitor closely for serotonin syndrome and TCA toxicity

QT-prolonging drugs (haloperidol, sotalol, amiodarone, clarithromycin, ondansetron) Additive QT prolongation; risk of torsades de pointes Avoid combination; if essential, ECG monitoring; correct electrolytes

Class IC antiarrhythmics (flecainide, propafenone) Additive cardiac conduction effects; CYP2D6 interaction Avoid combination

Sympathomimetics (adrenaline, noradrenaline, phenylephrine) Enhanced pressor response; hypertensive crisis risk Avoid or use with extreme caution; reduce sympathomimetic dose

Tramadol Serotonin syndrome risk; lowered seizure threshold Avoid combination

Cimetidine CYP inhibition; increased clomipramine levels Avoid cimetidine; use alternative H2 blocker or PPI

Interacting Drug Effect Management

Anticholinergic drugs (oxybutynin, trihexyphenidyl, antihistamines) Enhanced anticholinergic toxicity (urinary retention, constipation, confusion, hyperthermia) Minimise anticholinergic load; monitor for toxicity

Benzodiazepines, sedatives Additive CNS depression Caution; may need dose adjustment of either drug

Antihypertensives (especially alpha-blockers) Clomipramine may blunt antihypertensive effect; additive orthostatic hypotension Monitor blood pressure

Carbamazepine, phenytoin, phenobarbital CYP3A4 induction; reduced clomipramine levels Monitor clinical response; may need higher clomipramine dose

Rifampicin CYP induction; significantly reduced clomipramine levels Monitor antidepressant efficacy; consider alternative if possible

Warfarin Possible potentiation of anticoagulant effect Monitor INR closely; adjust warfarin dose as needed

Valproate May increase clomipramine levels Monitor for TCA toxicity

Alcohol Additive CNS depression; may lower seizure threshold Advise avoidance or strict moderation

Thyroid hormones Enhanced cardiovascular effects of clomipramine Monitor cardiovascular status

Antipsychotics Additive QT prolongation; increased plasma levels of both drugs ECG monitoring; dose adjustments may be needed

Triptans Theoretical serotonin syndrome risk Use with caution; monitor

• Dry mouth (very common)

• Constipation

• Sedation, drowsiness

• Weight gain

• Blurred vision

• Urinary hesitancy or retention

• Orthostatic hypotension

• Dizziness

• Tremor

• Tachycardia, palpitations

• Sexual dysfunction (decreased libido, erectile dysfunction, anorgasmia, delayed ejaculation)

• Sweating

• Headache

• Nausea (early, usually transient)

• Fatigue

Adverse Effect Clinical Significance

Seizures Dose-related; risk increases significantly above 250 mg/day; discontinue if seizure occurs; hospitalisation for evaluation

Cardiac arrhythmias QT prolongation, ventricular arrhythmias, heart block; ECG monitoring essential; discontinue if significant prolongation

Serotonin syndrome Life-threatening; occurs with serotonergic drug combinations; discontinue immediately; supportive care

Suicidal ideation/behaviour Enhanced risk in adolescents and young adults; close monitoring required in first weeks

Mania/hypomania May precipitate in bipolar patients; discontinue clomipramine and initiate mood stabiliser

Agranulocytosis Rare; presents with fever, sore throat, infection; check FBC; discontinue if confirmed

Hepatotoxicity Rare elevation of liver enzymes; very rare hepatic failure; discontinue if jaundice or significant LFT elevation

Paralytic ileus Rare; presents with severe constipation, abdominal distension; discontinue; supportive care

Acute urinary retention In predisposed patients; may require catheterisation

Hyperthermia Part of anticholinergic toxicity or serotonin syndrome; requires urgent management

Withdrawal syndrome Cholinergic rebound (nausea, vomiting, diarrhoea), sleep disturbance, anxiety on abrupt discontinuation; always taper gradually

Baseline:

• ECG (mandatory in patients >40 years, cardiac disease, or if QT-prolonging drugs co-prescribed; recommended in all patients)

• Blood pressure (lying and standing)

• Liver function tests

• Full blood count

• Serum sodium (especially elderly)

• Weight

• Psychiatric evaluation including suicide risk assessment

• Intraocular pressure assessment if glaucoma risk

After Initiation/Dose Change:

• Mental status, mood, and suicidal ideation assessment at 1, 2, and 4 weeks

• Blood pressure and heart rate

• Adverse effect review (anticholinergic effects, sedation)

• ECG if dose increased significantly or symptoms suggest cardiac effects

• Efficacy assessment

Long-term:

• ECG periodically (every 6–12 months in elderly or high-risk patients)

• Liver function tests annually or if symptomatic

• Weight monitoring every 3–6 months

• Blood pressure periodically

• Serum sodium in elderly (if on diuretics or symptomatic)

• Sexual function assessment

• Review of continued treatment need annually

• Dental review (dry mouth can cause dental caries)

• Clonil® (Intas) — 10 mg, 25 mg, 50 mg tablets; 75 mg SR

• Clofranil® (Torrent/Sun) — 10 mg, 25 mg, 50 mg, 75 mg tablets; SR formulation

• Clomac® (Sun Pharma) — 25 mg, 50 mg tablets

• Clomidep® (Cipla) — 25 mg, 50 mg tablets

• Anafranil® (Novartis — limited availability) — 25 mg tablets; 25 mg/2 mL injection

• Ocifril® (Intas) — 25 mg, 50 mg tablets

• Generic clomipramine (various manufacturers)

Note: Injectable formulation has limited availability; primarily stocked in tertiary care psychiatric facilities.

• Not included in NLEM

• Not under NPPA price control

• Available in government psychiatric hospitals

• Significant price variation between brands

• OCD gold standard: Clomipramine remains the most effective single medication for OCD; consider when SSRIs (fluvoxamine, fluoxetine, sertraline) at adequate doses for adequate duration have failed; may be combined with SSRIs under specialist supervision for refractory OCD

• Start low, go slow: Gradual titration minimises adverse effects and improves tolerability; patients often abandon treatment due to early anticholinergic burden if started too aggressively

• Anticholinergic management: Warn about dry mouth (sugar-free gum, frequent sips of water), constipation (dietary fibre, adequate hydration), and urinary hesitancy; reduce anticholinergic co-medications where possible

• Cardiac monitoring: ECG before starting (especially >40 years or cardiac risk) and periodically; QTc prolongation >500 ms or increase >60 ms from baseline warrants discontinuation or cardiology review

• Discontinuation: Never stop abruptly; taper over 4+ weeks (reduce by 25 mg every 1–2 weeks) to avoid cholinergic rebound and withdrawal symptoms

• Overdose danger: TCAs have narrow therapeutic index; intentional overdose can be fatal (cardiac arrhythmias, seizures); prescribe limited quantities in suicidal patients; consider safer alternatives

clomipramine; tricyclic antidepressant; TCA; OCD; depression; panic disorder; serotonergic TCA; anticholinergic; cardiac monitoring; seizure risk; psychiatry; suicidality-monitoring

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Psychiatry Standard Treatment Protocols

• Indian Psychiatric Society — Clinical Practice Guidelines for OCD

• ICMR Guidelines on Depression

• IAP Drug Formulary (paediatric dosing reference)

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics