Abstract
BackgroundGiven the complex nature of symptom presentation and medication regimens, psychiatric clinics may benefit from additional tools to personalize treatments. Utilizing pharmacogenetic information may be helpful in assessing unique responses to therapy. We report herein a case of wearing-off phenomena during treatment with aripiprazole long-acting injectable (LAI) and a proof of concept strategy of how pharmacogenetic information may be used to assess possible genetic factors and also hypothesize potential mechanisms for further study.Case presentationA 51-year-old African American male with schizoaffective disorder was referred to a psychiatric clinic for medication management. After unsuccessful trials of multiple antipsychotics, oral aripiprazole was initiated (up to 30 mg/day) and transitioned to aripiprazole LAI with symptom improvement. At a high dose of aripiprazole LAI (400 mg Q3wks), the patient experienced breakthrough symptoms approximately 3 days prior to his next injection. Various considerations were examined to explain his atypical dose requirements, including but not limited to pharmacogenetic influences. Pharmacogenetic testing ruled out genetic influences on drug metabolism but noted a -141C Del variant in the dopamine-D2 receptor (DRD2) gene associated in prior studies of poor-response to antipsychotics. At this time, a new formulation, aripiprazole lauroxil, was explored due to its availability in higher dose options. Transition to the new formulation (882 mg Q4wks) greatly improved and stabilized the patient’s symptoms with no breakthrough psychosis. Comparable daily dose equivalents were achieved with two different formulations due to the Q3wks vs Q4wks dosing strategies, although the two agents have some differences in pharmacokinetic profiles.ConclusionsWe report a case of a patient experiencing wearing-off symptoms with aripiprazole LAI who benefited from switching to aripiprazole lauroxil. Pharmacogenetic testing revealed normal activity for relevant metabolism pathways but a DRD2 -141C variant that may influence brain D2 expression and antipsychotic responsiveness. The clinical utility of DRD2 information and what to do with genotyping results has not been previously addressed, despite availability on clinical test panels. Our case report suggests further investigations of altered dosing strategies and receptor genotype sensitivities to pharmacokinetic factors may be helpful in understanding symptom re-emergence observed in some patients taking LAI antipsychotics.
Highlights
Given the complex nature of symptom presentation and medication regimens, psychiatric clinics may benefit from additional tools to personalize treatments
We report a case of a patient experiencing wearing-off symptoms with aripiprazole long-acting injectable (LAI) who benefited from switching to aripiprazole lauroxil
Our case report suggests further investigations of altered dosing strategies and receptor genotype sensitivities to pharmacokinetic factors may be helpful in understanding symptom re-emergence observed in some patients taking LAI antipsychotics
Summary
We report an African American patient who exhibited wearing-off symptoms with aripiprazole LAI and benefited from changing to the aripiprazole lauroxil formulation. The first is that some patients with partial response or symptom recurrence towards the end of the usual dosing interval for aripiprazole LAI may benefit from switching to an alternative formulation. The reasons for this are unclear and warrant further investigation. Our case suggests that some individuals may be sensitive to the pharmacokinetic differences between the aripiprazole LAI and lauroxil formulations at similar overall exposures, but the biological reasons for this are unknown. One hypothesis for further exploration is that genetic variation resulting in altered D2 expression or function may result in altered sensitivity to antipsychotic medications, requiring different dosing or drug selection strategies
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