Schedule H

Oral, Intramuscular

• Tablets: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg

• Orally Disintegrating Tablets (ODT): 5 mg, 10 mg, 15 mg

• Oral Solution: 1 mg/mL (limited availability)

• Injection (Short-acting IM): 7.5 mg/mL (9.75 mg/1.3 mL single-use vial)

Note: Long-acting injectable (LAI) formulation is NOT AVAILABLE in India.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Schizophrenia — Adults

Parameter Recommendation

Starting dose 10–15 mg orally once daily

Titration Adjust by 5 mg increments at intervals of ≥2 weeks based on response and tolerability

Usual maintenance dose 10–15 mg once daily

Maximum dose 30 mg/day

Clinical Notes:

• May be taken with or without food

• Onset of antipsychotic effect typically within 1–2 weeks; full response may take 4–6 weeks

• Lower starting dose (5–10 mg) if combined with CYP2D6 or CYP3A4 inhibitors

• Less sedating than other atypical antipsychotics; may be given in the morning

1. Bipolar I Disorder — Acute Manic or Mixed Episodes (Monotherapy or Adjunctive)

Parameter Recommendation

Starting dose 15 mg orally once daily

Titration May increase by 5–10 mg/day at intervals of ≥24 hours based on response

Usual maintenance dose 15–30 mg once daily

Maximum dose 30 mg/day

Clinical Notes:

• May be used as monotherapy or as adjunct to lithium or valproate

• More rapid titration acceptable in acute mania compared to schizophrenia

• Continue at effective dose for maintenance therapy

1. Bipolar I Disorder — Maintenance Therapy

Parameter Recommendation

Starting dose Continue dose effective during acute episode

Titration Not applicable for maintenance

Usual maintenance dose 15–30 mg once daily

Maximum dose 30 mg/day

Clinical Notes:

• Reassess periodically for continued need

• May be used as monotherapy or adjunct to mood stabilisers

1. Acute Agitation in Schizophrenia or Bipolar Mania — Intramuscular (Short-Term)

Parameter Recommendation

Starting dose 9.75 mg IM as single dose (deep intramuscular injection)

Repeat dosing 5.25–9.75 mg IM may be given at intervals of ≥2 hours if required

Maximum dose 30 mg/day (IM)

Clinical Notes:

• For short-term use only in acute agitation settings

• Transition to oral therapy as soon as clinically feasible

• Do not administer IV or subcutaneously

• Monitor for orthostatic hypotension post-injection

• Ensure adequate hydration

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Major Depressive Disorder (Adjunct to Antidepressants) Starting: 2–5 mg/day; Maintenance: 2–15 mg/day 6–12 weeks initially; long-term if effective OFF-LABEL; Specialist only; Evidence: Multiple international RCTs support adjunctive use; Limited Indian tertiary centre experience

Tourette Syndrome Starting: 2 mg/day; Maintenance: 2–20 mg/day Long-term OFF-LABEL; Specialist only; Evidence: International RCTs; Use in refractory cases

Treatment-Resistant OCD (Augmentation) 5–15 mg/day added to SSRI 8–12 weeks trial OFF-LABEL; Specialist only; Evidence: RCTs show modest benefit

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Schizophrenia — Adolescents (Age 13–17 Years)

Parameter Recommendation

Starting dose 2 mg orally once daily for 2 days

Titration Increase to 5 mg once daily for 2 days, then titrate by 5 mg increments at weekly intervals

Usual maintenance dose 10 mg once daily

Maximum dose 30 mg/day

Clinical Notes:

• Target dose 10 mg/day; doses above 10 mg did not show increased efficacy in adolescent trials

• Monitor for extrapyramidal symptoms, weight gain, metabolic changes

1. Bipolar I Disorder — Acute Manic or Mixed Episodes (Age 10–17 Years)

Parameter Recommendation

Starting dose 2 mg orally once daily for 2 days

Titration Increase to 5 mg once daily for 2 days, then titrate by 5 mg increments at weekly intervals

Usual maintenance dose 10 mg once daily

Maximum dose 30 mg/day

Clinical Notes:

• Target dose 10 mg/day in paediatric bipolar mania

• Continue at effective dose for maintenance

Secondary Indications – Paediatrics (Off-label, if any)

Indication Age Dose Notes

Irritability Associated with Autism Spectrum Disorder ≥6 years Starting: 2 mg/day; Target: 5–10 mg/day; Maximum: 15 mg/day OFF-LABEL in India; Specialist only (Child Psychiatry); Evidence: FDA-approved indication internationally; RCTs support efficacy; Very limited Indian experience

Tourette Syndrome ≥6 years Starting: 2 mg/day; Maintenance: 5–10 mg/day; Maximum: 20 mg/day OFF-LABEL; Specialist only; Evidence: International RCTs

Safety Monitoring in Paediatric Use:

• Weight, height, BMI at each visit

• Fasting glucose and lipid profile at baseline, 12 weeks, then annually

• Extrapyramidal symptoms assessment

• Suicidal ideation monitoring (especially during initial treatment)

• Prolactin levels if symptoms suggest hyperprolactinaemia

Not recommended below 6 years of age except under strict specialist supervision in tertiary centres for rare indications.

• Aripiprazole and its active metabolite are minimally renally excreted (<1%)

• Use with caution in patients who are volume-depleted or on concurrent antihypertensives (increased hypotension risk)

• Known hypersensitivity to aripiprazole or any excipient

• IM formulation: Do not administer intravenously or subcutaneously

• Comatose state or severe CNS depression (acute alcohol intoxication, sedative overdose)

• Cardiovascular disease — risk of orthostatic hypotension, particularly during initial titration

• History of seizure disorder or conditions that lower seizure threshold

• Cerebrovascular disease — increased stroke risk in elderly with dementia

• Diabetes mellitus or risk factors for hyperglycaemia — monitor glucose

• Risk of tardive dyskinesia with prolonged use

• Neuroleptic Malignant Syndrome (NMS) — monitor for early signs (hyperthermia, rigidity, altered mental status)

• Dysphagia risk — aspiration pneumonia possible

• Impulse control disorders — pathological gambling, hypersexuality, compulsive eating reported; monitor and counsel

• Suicidal ideation — particularly in young adults and during initial treatment phase

• Body temperature dysregulation — avoid strenuous exercise, dehydration, extreme heat

• Leukopenia/Neutropenia — patients with history of low WBC or drug-induced leukopenia require monitoring

Parameter Details

Risk Category Limited human data; animal studies show developmental toxicity at high doses

Recommendation Avoid if possible, especially in first trimester; use only if benefit clearly outweighs risk

Known Risks Third trimester exposure may cause extrapyramidal symptoms and withdrawal symptoms in neonates

Preferred Alternatives Haloperidol (acute psychosis) or quetiapine (more pregnancy data) — specialist psychiatric and obstetric input essential

Monitoring If used in third trimester, monitor neonate for extrapyramidal symptoms, sedation, feeding difficulties, respiratory distress

Parameter Details

Compatibility Not recommended; aripiprazole and active metabolite detected in breast milk

Drug Levels in Milk Low to moderate levels reported

Preferred Alternatives Olanzapine or quetiapine have slightly more lactation safety data; specialist input recommended

Infant Monitoring If breastfeeding continues, monitor infant for sedation, irritability, poor feeding, and adequate weight gain

Parameter Recommendation

Starting dose 5 mg orally once daily (lower than adults)

Titration Slower titration — every 2 weeks; smaller increments

Special Risks Increased risk of orthostatic hypotension, falls, confusion, akathisia, sedation; age-related decline in hepatic function may increase drug levels

Dementia-Related Psychosis NOT approved and NOT recommended — increased risk of cerebrovascular adverse events and death in elderly patients with dementia-related psychosis

Monitoring Blood pressure (orthostatic), fall risk assessment, cognitive function

Interacting Drug Mechanism / Effect Recommendation

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) Increased aripiprazole plasma levels Reduce aripiprazole dose to half; monitor for adverse effects

Strong CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) Increased aripiprazole plasma levels Reduce aripiprazole dose to half; monitor for adverse effects

Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampicin) Decreased aripiprazole plasma levels by ~70% Double the aripiprazole dose; consider alternative mood stabiliser

Combined CYP2D6 + CYP3A4 inhibitors Marked increase in aripiprazole levels Reduce aripiprazole dose to one-quarter of usual dose

Other CNS depressants (benzodiazepines, opioids, alcohol) Additive CNS depression Use with caution; avoid alcohol; monitor for excessive sedation

QT-prolonging drugs (although aripiprazole has minimal QT effect) Potential additive effect Monitor ECG if multiple QT-prolonging drugs used

Interacting Drug Mechanism / Effect Recommendation

Antihypertensives Additive hypotensive effect; increased orthostatic hypotension Monitor blood pressure; dose adjustment of antihypertensive may be needed

Lithium No significant pharmacokinetic interaction; commonly combined Monitor for additive CNS effects; standard lithium monitoring

Valproate No significant pharmacokinetic interaction; commonly combined in bipolar disorder Monitor for sedation

SSRIs/SNRIs (non-CYP2D6 inhibitors) Pharmacodynamic interaction; possible serotonin syndrome risk Monitor for serotonin syndrome symptoms

Levodopa / Dopamine agonists Aripiprazole may antagonise dopaminergic effects Avoid in Parkinson's disease; monitor if unavoidable

Metoclopramide Both have dopamine receptor activity; additive EPS risk Avoid combination

Anticholinergics May counteract extrapyramidal effects but add cognitive impairment Use judiciously; assess anticholinergic burden

• Akathisia (restlessness) — most common; dose-dependent

• Insomnia

• Headache

• Nausea and vomiting

• Dizziness

• Anxiety / Agitation (especially early in treatment)

• Constipation

• Fatigue

• Blurred vision

• Tremor

• Weight gain (generally less than olanzapine, clozapine, quetiapine)

• Dyspepsia

Adverse Effect Clinical Action

Neuroleptic Malignant Syndrome (NMS) Discontinue immediately; supportive care; ICU admission may be required; do not rechallenge

Tardive Dyskinesia Consider dose reduction or discontinuation; may be irreversible; regular AIMS assessment

Severe Extrapyramidal Symptoms (acute dystonia, severe parkinsonism) Dose reduction; anticholinergic agents may help; consider switching antipsychotic

Seizures Discontinue or reduce dose; neurological evaluation

Hyperglycaemia / Diabetic Ketoacidosis Monitor glucose; endocrinology referral; may require discontinuation

Orthostatic Hypotension with Syncope Reduce dose; ensure adequate hydration; falls precautions

Leukopenia / Neutropenia Monitor CBC; discontinue if ANC <1000/mm³

Impulse Control Disorders (pathological gambling, hypersexuality) Dose reduction or discontinuation; counsel patient and family

Suicidal Ideation (especially in young adults) Close monitoring; psychiatric evaluation; may require discontinuation

Cerebrovascular Events (in elderly with dementia) Discontinue; neurological evaluation

First month Weekly assessment for EPS, akathisia, suicidality (especially in youth); blood pressure

At 12 weeks Weight, BMI, fasting glucose, lipid profile

Every 3 months Weight, BMI, blood pressure

Every 6–12 months Fasting glucose/HbA1c, lipid profile, movement disorder assessment (AIMS for tardive dyskinesia)

Ongoing Clinical assessment for akathisia, EPS, metabolic changes, impulse control issues, suicidality

Monotherapy:

• Arpizol (Torrent)

• Arip MT (Intas) — Mouth dissolving tablets

• Aripra (Sun Pharma)

• Ariza (Zydus)

• Abilify (Otsuka — limited availability)

• Asprito (Mankind)

• Aripiprax (Cipla)

• Pipra (Alkem)

Fixed-Dose Combinations:

• With Trihexyphenidyl: Various brands (for EPS prophylaxis — use judiciously)

Note: FDCs with anticholinergics are generally not recommended as routine first-line; assess EPS before adding anticholinergic.

• Not included in NLEM; pricing not NPPA-controlled

• Significant price variation across brands

• Government supply available in some tertiary psychiatric centres

• Unique dopamine partial agonist mechanism — provides antipsychotic effect while causing less hyperprolactinaemia and potentially less negative symptom worsening than full D2 antagonists

• Lower metabolic liability is a major advantage — causes less weight gain, dyslipidaemia, and glucose dysregulation compared to olanzapine, clozapine, and quetiapine; preferred choice in patients with metabolic concerns

• Akathisia is the most common dose-limiting adverse effect — occurs in up to 25% of patients; often mistaken for anxiety or worsening agitation; slow titration and low starting doses reduce risk; may respond to dose reduction, propranolol, or benzodiazepines

• Less sedating than most other atypical antipsychotics — useful in patients with prominent negative symptoms or those who cannot tolerate sedation; can be given in the morning

• CYP450 interactions are clinically significant — always check for CYP3A4 and CYP2D6 inhibitors/inducers; dose adjustment mandatory with strong inhibitors

• Monitor for impulse control disorders — pathological gambling, compulsive shopping, and hypersexuality are increasingly recognised; counsel patients and families at initiation

Aripiprazole; schizophrenia; bipolar disorder; atypical antipsychotic; dopamine partial agonist; akathisia; low metabolic risk; weight-neutral; impulse control; youth-monitoring; Schedule H

RxIndia v1.0 — 03 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine — Psychiatry chapter

• AIIMS Psychiatry Department Treatment Protocols

• Indian Psychiatric Society Clinical Practice Guidelines

• ICMR Guidelines for Mental Health

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• International RCTs (for off-label indications — marked accordingly)