Is it safe to increase Abilify (aripiprazole) to 10 mg in a patient taking duloxetine and Augmentin (amoxicillin/clavulanate)?

Increasing Abilify to 10 mg While Taking Duloxetine and Augmentin

Yes, it is safe to increase aripiprazole (Abilify) to 10 mg in a patient taking duloxetine and Augmentin, but you must reduce the aripiprazole dose by 50% due to the significant drug interaction between aripiprazole and duloxetine. 1

Critical Drug Interaction: Aripiprazole and Duloxetine

The FDA label for aripiprazole explicitly requires dosage adjustments when coadministered with CYP2D6 inhibitors like duloxetine. 1 Duloxetine is a moderate-to-strong CYP2D6 inhibitor, and since aripiprazole is metabolized primarily through CYP3A4 and CYP2D6 pathways, this interaction can significantly increase aripiprazole plasma concentrations. 1, 2

Recommended Dosing Adjustment

• If your intended dose is 10 mg aripiprazole daily, start with 5 mg daily instead (50% dose reduction) when coadministered with duloxetine 1
• The FDA label states: "Patients taking concomitant CYP2D6 inhibitors should have their aripiprazole dose reduced to one-half of the usual dose" 1
• When duloxetine is eventually discontinued, gradually increase aripiprazole back to the original intended dose over 1-2 weeks 1

Clinical Evidence of This Interaction

A documented case report demonstrated dangerously elevated aripiprazole concentrations (1100 ng/mL versus therapeutic range of 100-200 ng/mL) in a patient taking aripiprazole 50 mg daily with duloxetine 60 mg daily and ritonavir-boosted antiretrovirals. 3 The patient developed confusion, loss of coordination, and required hospitalization. 3 While this case involved multiple CYP inhibitors and a supratherapeutic aripiprazole dose, it illustrates the potential severity of this interaction.

Augmentin (Amoxicillin/Clavulanate) Considerations

Augmentin does not interact with aripiprazole or duloxetine through cytochrome P450 pathways and requires no dose adjustment. 4 Amoxicillin/clavulanate is renally eliminated and does not significantly affect CYP enzymes. The antibiotic can be safely continued without concern for psychiatric medication interactions.

Monitoring Parameters

Monitor for the following during the first 2-4 weeks after initiating or increasing aripiprazole:

• Extrapyramidal symptoms (EPS): akathisia, tremor, rigidity, though aripiprazole has a lower EPS risk than typical antipsychotics 2, 5
• Sedation and somnolence: common early side effects that may be exacerbated by the duloxetine combination 2, 6
• Akathisia: the most common movement-related side effect with aripiprazole 2
• Weight gain: aripiprazole has a relatively low propensity for weight gain compared to other atypicals 2

Therapeutic Efficacy Timeline

• Aripiprazole is effective as early as the first or second week of treatment for schizophrenia and mood symptoms 2
• The standard therapeutic dose is 10-15 mg daily, with no additional benefit demonstrated at higher doses 1, 2
• For augmentation therapy in depression (which may be relevant given duloxetine use), aripiprazole shows effectiveness within weeks, with remission rates improving from 34.5% at 6 months to 43.3% at 12 months 6

Common Pitfalls to Avoid

• Do not use the full 10 mg dose without accounting for the duloxetine interaction—this is the most critical error to avoid 1
• Do not abruptly increase aripiprazole to the full dose when duloxetine is discontinued—taper up over 1-2 weeks 1
• Do not assume Augmentin requires any psychiatric medication adjustment—it does not interact 4
• Be aware that if the patient is a CYP2D6 poor metabolizer (genetic polymorphism), the interaction effect will be even more pronounced 1, 3