Summary

Fluoxetine significantly inhibits the metabolism of aripiprazole through CYP2D6 enzyme inhibition, leading to increased aripiprazole plasma concentrations. This interaction requires careful monitoring and potential dose adjustments to prevent adverse effects while maintaining therapeutic efficacy.

Introduction

Aripiprazole is an atypical antipsychotic medication primarily used to treat schizophrenia, bipolar disorder, and major depressive disorder as adjunctive therapy. It belongs to the quinolinone class and works as a partial dopamine D2 receptor agonist. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression, anxiety disorders, obsessive-compulsive disorder, and bulimia nervosa. Both medications are frequently prescribed together in clinical practice for patients with comorbid psychiatric conditions.

Mechanism of Interaction

The interaction between aripiprazole and fluoxetine occurs through cytochrome P450 enzyme inhibition. Fluoxetine is a potent inhibitor of CYP2D6, the primary enzyme responsible for aripiprazole metabolism. When fluoxetine inhibits CYP2D6, it significantly reduces the clearance of aripiprazole, leading to increased plasma concentrations of the antipsychotic. This pharmacokinetic interaction can result in aripiprazole levels that are 2-3 times higher than expected, potentially increasing the risk of dose-related adverse effects.

Risks and Symptoms

The primary clinical risk of this interaction is the potential for increased aripiprazole-related adverse effects due to elevated plasma concentrations. These may include extrapyramidal symptoms (tremor, rigidity, akathisia), sedation, weight gain, metabolic changes, and cardiovascular effects such as QT prolongation. Patients may also experience increased risk of tardive dyskinesia with prolonged exposure to higher aripiprazole levels. The interaction is considered clinically significant and requires proactive management to ensure patient safety while maintaining therapeutic benefits.

Management and Precautions

When co-prescribing aripiprazole and fluoxetine, consider reducing the aripiprazole dose by 50% to account for the decreased clearance. Monitor patients closely for signs of aripiprazole toxicity, including movement disorders, excessive sedation, and metabolic changes. Regular assessment of therapeutic response and adverse effects is essential. Consider therapeutic drug monitoring if available. Alternative antidepressants with minimal CYP2D6 inhibition (such as sertraline or citalopram) may be considered if the interaction poses significant clinical concerns. Always consult current prescribing information and consider individual patient factors when making dosing decisions.

Aripiprazole interactions with food and lifestyle

Alcohol: Aripiprazole may enhance the sedative effects of alcohol. Patients should avoid or limit alcohol consumption while taking aripiprazole as it can increase drowsiness, dizziness, and impair cognitive function. Grapefruit juice: May increase aripiprazole blood levels by inhibiting CYP3A4 metabolism, though this interaction is generally considered minor and not routinely contraindicated in clinical practice.

Fluoxetine interactions with food and lifestyle

Alcohol: Fluoxetine may increase the sedative effects of alcohol and impair cognitive and motor performance. Patients should avoid or limit alcohol consumption while taking fluoxetine. Grapefruit juice: May increase fluoxetine blood levels, though this interaction is generally considered minor. St. John's Wort: Should be avoided as it may increase the risk of serotonin syndrome when combined with fluoxetine.