Dosing Recommendations of Aripiprazole Depot with Strong Cytochrome P450 3A4 Inhibitors: A Relapse Risk

A 50-year-old male patient with comorbid human immunodeficiency virus developed a relapse of bipolar disorder after a switch from oral aripiprazole 10 mg/day to intramuscular aripiprazole depot 200 mg every 28 days plus oral aripiprazole 5 mg/day. The patient was concomitantly taking lopinavir, saquinavir, ritonavir, silybum marianum extract, and omeprazole. Only 1 week after the switch, the patient developed mood swings, irritability, depressive mood, and lack of drive. The oral aripiprazole was increased again to stabilize the patient. The measured trough drug concentration of aripiprazole was low and may be correlated to the relapse. When oral aripiprazole was increased back to 10 mg again, the depressive symptoms subsided. The dose of the next depot injection was increased to 300 mg and that of oral aripiprazole decreased back to 5 mg/day. Because trough drug concentrations were still low after 28 days, the depot dose was increased to 400 mg every 28 days, which is double that recommended in the prescriber's information. Two months after the initial switch from oral to intramuscular aripiprazole, the patient's mood stabilized on aripiprazole depot 400 mg every 28 days. More clinical data, especially regarding the pharmacokinetic drug interactions of aripiprazole depot are needed to improve dosing recommendations, and prevent relapses or adverse drug events. Genetic polymorphisms may play an important role in the clinical relevance of drug interactions concerning aripiprazole depot.