What are the recommended doses of aripiprazole and fluvoxamine (selective serotonin reuptake inhibitor) when used concomitantly?

Aripiprazole and Fluvoxamine Concomitant Dosing

When using aripiprazole and fluvoxamine together, reduce the aripiprazole dose to half of the usual dose due to significant drug-drug interaction via CYP2D6 inhibition. 1

Dose Adjustment Algorithm

Aripiprazole Dose Reduction Required

• Standard aripiprazole dose: 10-15 mg/day for schizophrenia or other indications 1
• Adjusted dose with fluvoxamine: Reduce aripiprazole to 50% of usual dose (5-7.5 mg/day) 1
• Mechanism: Fluvoxamine is a strong CYP2D6 inhibitor that significantly increases aripiprazole exposure 2

Fluvoxamine Dosing

• Initial dose: 50 mg twice daily 2
• Maximum dose: 150 mg twice daily 2
• Titration: Increase gradually as tolerated for the underlying condition being treated 2

Critical Drug Interaction Considerations

Why This Combination Requires Dose Adjustment

Fluvoxamine inhibits multiple CYP450 enzymes (CYP1A2, CYP2C19, CYP2C9, CYP3A4, and CYP2D6), creating significant potential for drug-drug interactions. 2 When combined with aripiprazole:

• Aripiprazole is metabolized by both CYP3A4 and CYP2D6 1
• Strong CYP2D6 inhibitors (including fluvoxamine) increase aripiprazole exposure substantially 1
• The FDA label explicitly recommends dose reduction when aripiprazole is combined with strong CYP2D6 inhibitors 1

Monitoring Requirements

• Start low and titrate slowly: When initiating the second serotonergic drug, monitor closely in the first 24-48 hours after dosage changes 2
• Watch for serotonin syndrome: Symptoms include mental status changes, neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 2
• Monitor for increased aripiprazole effects: Sedation, extrapyramidal symptoms, or other adverse effects may be amplified 1

Practical Implementation

When Starting Combination Therapy

1. If patient is already on aripiprazole: Reduce dose by 50% when adding fluvoxamine 1
2. If patient is already on fluvoxamine: Start aripiprazole at 50% of usual starting dose (5 mg/day instead of 10 mg/day) 1
3. Allow 2 weeks for steady state: Aripiprazole requires approximately 14 days to reach steady-state concentrations 1, 3

When Discontinuing Fluvoxamine

• Restore original aripiprazole dose when fluvoxamine is withdrawn from combination therapy 1
• Titrate back gradually over 1-2 weeks to avoid abrupt changes in aripiprazole levels 1

Common Pitfalls to Avoid

• Do not use standard aripiprazole doses with fluvoxamine without adjustment—this will result in excessive aripiprazole exposure 1
• Fluvoxamine has greater drug interaction potential compared to other SSRIs due to its broad CYP450 inhibition profile 2
• Discontinuation syndrome risk: Fluvoxamine is associated with discontinuation syndrome; taper over 10-14 days when stopping 2