Schedule H

Oral

• Immediate-release (IR) tablets: 10 mg, 12.5 mg, 20 mg, 25 mg, 30 mg, 40 mg

• Controlled-release (CR) tablets: 12.5 mg, 25 mg, 37.5 mg

• Oral suspension: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD)

Using Immediate-Release (IR) Formulation:

Parameter Recommendation

Starting dose 20 mg once daily in the morning

Titration Increase by 10 mg/day at intervals of at least 1 week based on clinical response

Usual maintenance dose 20–40 mg once daily

Maximum dose 50 mg/day

Using Controlled-Release (CR) Formulation:

Parameter Recommendation

Starting dose 25 mg once daily in the morning

Titration Increase by 12.5 mg/day at intervals of at least 1 week

Usual maintenance dose 25–50 mg once daily

Maximum dose 62.5 mg/day

Clinical Notes:

• Administer in the morning with or without food

• CR tablets should be swallowed whole; do not crush or chew

• Therapeutic response typically observed within 2–4 weeks

• Taper gradually when discontinuing (high withdrawal risk)

1. Generalised Anxiety Disorder (GAD)

Parameter Recommendation

Starting dose 20 mg once daily (IR)

Titration Increase by 10 mg/day at weekly intervals if needed

Usual maintenance dose 20–40 mg once daily

Maximum dose 50 mg/day

1. Panic Disorder (with or without Agoraphobia)

Parameter Recommendation

Starting dose 10 mg once daily (lower start to minimise initial anxiety exacerbation)

Titration Increase by 10 mg/day every 1–2 weeks

Usual maintenance dose 30–40 mg once daily

Maximum dose 60 mg/day

Clinical Notes:

• Start at lower dose as paroxetine may transiently worsen panic symptoms initially

• Full therapeutic effect may take 8–12 weeks

1. Obsessive-Compulsive Disorder (OCD)

Parameter Recommendation

Starting dose 20 mg once daily

Titration Increase by 10 mg/day at weekly intervals

Usual maintenance dose 40–60 mg once daily

Maximum dose 60 mg/day

Clinical Notes:

• Higher doses generally required for OCD compared to depression

• Response may take 10–12 weeks; continue for at least 1–2 years if effective

1. Social Anxiety Disorder (Social Phobia)

Parameter Recommendation

Starting dose 20 mg once daily

Titration Increase by 10 mg/day at weekly intervals if needed

Usual maintenance dose 20–40 mg once daily

Maximum dose 60 mg/day

1. Post-Traumatic Stress Disorder (PTSD)

Parameter Recommendation

Starting dose 20 mg once daily

Titration Increase by 10 mg/day at weekly intervals based on response

Usual maintenance dose 20–40 mg once daily

Maximum dose 50 mg/day

Secondary Indications — Adults (Off-label)

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — Paroxetine is not approved for routine paediatric use in India due to concerns regarding efficacy and increased risk of suicidal ideation in children and adolescents.

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Obsessive-Compulsive Disorder (OCD) ≥7 years Starting: 10 mg once daily; Titration: increase by 10 mg/week; Usual maintenance: 20–40 mg/day; Maximum: 50 mg/day OFF-LABEL — Child psychiatrist supervision mandatory. Not first-line; fluvoxamine or sertraline preferred for paediatric OCD.

Major Depressive Disorder ≥12 years Starting: 10 mg once daily; Titration: increase by 10 mg/week; Maximum: 40 mg/day OFF-LABEL — Specialist only. Not recommended as first-line due to limited efficacy data and suicidality concerns in adolescents. Fluoxetine preferred.

Minimum Age Statement: Not recommended in children below 7 years of age. Use in patients 7–18 years only under child and adolescent psychiatrist supervision with documented rationale and enhanced monitoring.

Safety Monitoring:

• Weekly assessment for suicidal ideation, self-harm behaviour, and mood changes during first 4 weeks

• Monitor for behavioural activation, agitation, hostility

• Weight and growth monitoring

• Review of treatment need every 3 months

• Concurrent use with monoamine oxidase inhibitors (MAOIs) including phenelzine, tranylcypromine, selegiline, moclobemide; minimum 14-day washout required before or after MAOI

• Concurrent use with linezolid or intravenous methylene blue (MAOI activity)

• Concurrent use with thioridazine (risk of serious ventricular arrhythmias and sudden death due to QT prolongation)

• Concurrent use with pimozide (QT prolongation risk via CYP2D6 inhibition)

• Known hypersensitivity to paroxetine or any excipient

• History of seizure disorder — may lower seizure threshold

• Suicidal ideation — enhanced risk in first weeks of treatment, especially in patients under 25 years; close monitoring required

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

• Bleeding disorders or concurrent anticoagulant/antiplatelet therapy — SSRI-induced platelet dysfunction increases bleeding risk

• Hyponatraemia risk — especially in elderly, patients on diuretics, or those with SIADH history

• Narrow-angle glaucoma — may increase intraocular pressure; mydriasis reported

• Hepatic or renal impairment — requires dose adjustment

• Cardiac disease — use with caution; limited data on QT effects at therapeutic doses

• Diabetes mellitus — may alter glycaemic control

• Concurrent use with drugs affecting serotonin — risk of serotonin syndrome

• History of mania — may precipitate switch

• Abrupt discontinuation — high risk of discontinuation syndrome; always taper

Parameter Recommendation

Safety Category Increased risk of congenital cardiac malformations (particularly ventricular and atrial septal defects) with first-trimester exposure; also associated with persistent pulmonary hypertension of newborn (PPHN) and neonatal adaptation syndrome

Preferred Alternatives Sertraline is preferred first-line SSRI during pregnancy in Indian obstetric psychiatry practice; fluoxetine is alternative

When to Use Only if clearly necessary when other SSRIs have failed or are not tolerated; requires joint obstetric-psychiatry decision

Monitoring Fetal echocardiography if first-trimester exposure; fetal growth surveillance; neonatal monitoring for withdrawal symptoms, respiratory distress, feeding difficulties

Parameter Recommendation

Breastfeeding Compatibility Compatible with caution; one of the SSRIs with lower infant exposure

Drug Levels in Milk Low (relative infant dose typically <3%)

Preferred Alternatives Sertraline generally preferred for breastfeeding mothers; paroxetine is acceptable alternative

Infant Monitoring Monitor for drowsiness, irritability, poor feeding, weight gain; observe for withdrawal symptoms if maternal dose changed abruptly

Parameter Recommendation

Starting dose 10 mg once daily (IR) or 12.5 mg once daily (CR)

Titration Slower titration at 1–2 week intervals; increase by 10 mg increments

Maximum dose 40 mg/day

Additional Risks Increased susceptibility to hyponatraemia (SIADH); sedation; cognitive impairment; falls risk; drug interactions due to polypharmacy; bleeding risk if on anticoagulants/antiplatelets

Monitoring Serum sodium (baseline and periodic); renal function; mental status; fall risk assessment

Interacting Drug Mechanism/Effect Management

MAOIs (phenelzine, tranylcypromine, selegiline, moclobemide) Risk of life-threatening serotonin syndrome Contraindicated; 14-day washout required

Linezolid, IV methylene blue MAOI activity; serotonin syndrome risk Avoid concurrent use; if linezolid essential, discontinue paroxetine and monitor

Thioridazine Paroxetine inhibits CYP2D6; increased thioridazine levels; risk of QT prolongation, torsades de pointes Contraindicated

Pimozide CYP2D6 inhibition; increased pimozide levels; QT prolongation Contraindicated

Tamoxifen Paroxetine potently inhibits CYP2D6; reduces conversion to active metabolite (endoxifen); reduced tamoxifen efficacy Avoid concurrent use; use alternative SSRI (sertraline, escitalopram, venlafaxine)

Tramadol Serotonin syndrome risk; reduced analgesic effect (blocked conversion to active metabolite) Avoid if possible; use alternative analgesic

Triptans (sumatriptan, etc.) Additive serotonergic effects; serotonin syndrome risk Use with caution; monitor for serotonin syndrome symptoms

Warfarin Increased bleeding risk via platelet serotonin depletion and possible pharmacokinetic interaction Monitor INR closely; dose adjustment may be needed

Interacting Drug Effect Management

NSAIDs (ibuprofen, diclofenac, aspirin) Additive GI bleeding risk via platelet dysfunction Use with caution; consider gastroprotection; avoid long-term combination if possible

Carbamazepine, phenytoin, phenobarbital CYP inducers; may reduce paroxetine plasma levels Monitor clinical response; may need paroxetine dose increase

Rifampicin Strong CYP inducer; significantly reduces paroxetine levels Monitor antidepressant efficacy; consider alternative antidepressant or higher paroxetine dose

CYP2D6 substrates (metoprolol, propranolol, codeine, dextromethorphan, atomoxetine, tricyclic antidepressants) Paroxetine inhibits CYP2D6; increased levels of substrate drugs Reduce dose of CYP2D6 substrate; monitor for toxicity (e.g., bradycardia with beta-blockers)

Digoxin May decrease digoxin plasma levels (mechanism unclear) Monitor digoxin levels

Alcohol Enhanced CNS depression; may worsen depression Advise avoidance or moderation

Lithium Possible enhanced serotonergic effects; case reports of serotonin syndrome Monitor for serotonin syndrome; lithium levels not typically affected

Antipsychotics (risperidone, haloperidol) CYP2D6 inhibition; increased antipsychotic levels Monitor for extrapyramidal symptoms and other adverse effects

• Nausea (most common, usually transient)

• Drowsiness, sedation, fatigue

• Insomnia

• Dry mouth

• Constipation

• Dizziness

• Headache

• Excessive sweating

• Sexual dysfunction (decreased libido, anorgasmia, delayed ejaculation — very common)

• Appetite changes (decreased or increased)

• Weight gain (with long-term use)

• Tremor

• Asthenia

Adverse Effect Clinical Significance

Serotonin syndrome Life-threatening; characterised by hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes; discontinue immediately; supportive care and cyproheptadine

Suicidal ideation/behaviour Increased risk in adolescents and young adults; enhanced monitoring required in first weeks

Hyponatraemia (SIADH) Particularly in elderly; presents with confusion, seizures; check sodium; discontinue if severe

Seizures Dose-related risk; discontinue if seizure occurs

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

Bleeding (GI, intracranial, ecchymoses) Due to platelet serotonin depletion; increased risk with concurrent anticoagulants/NSAIDs

QT prolongation Primarily in overdose or with interacting drugs; ECG monitoring if concerned

Stevens-Johnson Syndrome Rare; discontinue immediately if mucocutaneous reaction occurs

Discontinuation syndrome Very common with paroxetine due to short half-life; symptoms include dizziness, sensory disturbances, anxiety, nausea, tremor; always taper gradually

Akathisia Restlessness; may be mistaken for worsening anxiety

Baseline:

• Mental status assessment including suicide risk evaluation

• Serum sodium (especially in elderly or those on diuretics)

• Renal and hepatic function

• Weight

• Blood pressure

• Review of concomitant medications for interactions

After Initiation/Dose Change:

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

• Assess for emergent anxiety, agitation, or insomnia (especially in panic disorder)

• Monitor for adverse effects (nausea, sedation, sexual dysfunction)

• Serum sodium at 2–4 weeks in high-risk patients

Long-term:

• Weight and metabolic parameters every 3–6 months

• Sexual function assessment periodically

• Serum sodium periodically in elderly

• Annual review of continued treatment need

• Gradual taper plan when discontinuing

• Paxidep® (Cipla)

• Parotin® (Sun Pharma)

• Xet® (Sun Pharma)

• Pari® (Intas)

• Pexep® (Intas)

• Paroxet® (Cadila)

• Paro CR® (Controlled-release formulations)

• Seroxat® (GSK — limited availability)

Note: Fixed-dose combinations with paroxetine are not commonly marketed in India.

• Not included in NLEM

• Not under NPPA price control

• Available in government hospital formularies in some states

• Widely available through private retail pharmacies

• Discontinuation syndrome: Paroxetine has the highest risk of SSRI discontinuation syndrome due to its short half-life and potent serotonin reuptake inhibition — always taper over 4+ weeks; reduce by 10 mg every 1–2 weeks

• Sexual dysfunction: Very common (up to 70%); more pronounced than some other SSRIs; consider bupropion augmentation or switch if problematic

• Sedation profile: More sedating than fluoxetine or sertraline — may be beneficial for anxious/insomnia-predominant presentations; dose at bedtime if sedation problematic

• Anticholinergic effects: Has mild anticholinergic activity (dry mouth, constipation) — more pronounced than other SSRIs; caution in elderly and those with urinary retention

• Pregnancy avoidance: Not preferred SSRI in pregnancy due to cardiac malformation risk; switch to sertraline if planning pregnancy

• CYP2D6 inhibition: Potent inhibitor — causes multiple drug interactions; particularly important with tamoxifen (avoid), codeine (ineffective), and cardiovascular drugs

• Start low in panic: Begin at 10 mg to avoid paradoxical anxiety worsening; gradual titration essential

paroxetine; SSRI; depression; anxiety; OCD; panic disorder; PTSD; social anxiety; pregnancy-risk; discontinuation-syndrome; CYP2D6-inhibitor; suicidality-monitoring; elderly-caution

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Psychopharmacology Protocols

• Indian Psychiatric Society — Clinical Practice Guidelines for Depression and Anxiety Disorders

• ICMR Guidelines on Mental Health (2022)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• International RCTs (for PMDD, vasomotor symptoms — off-label indications only)