One Plus One Sometimes Equals More Than Two: Long-acting Injectable Aripiprazole Adjunction in Clozapine-Resistant Schizophrenia

In this report, we present a patient whose positive symptoms did not improve despite being treated with clozapine monotherapy at a therapeutic dose for 4 months, and whose symptoms began to resolve after aripiprazole long-acting injection adjunction to clozapine. A 22-year-old man was diagnosed as having schizophrenia last year in his first admission, with symptoms of auditory hallucinations, persecutory delusions, and associated social withdrawal. His positive symptoms did not improve despite being treated with risperidone, olanzapine, and paliperidone. Oral clozapine monotherapy was planned, and the daily dose was increased to provide a therapeutic plasma clozapine concentration and measured as effective (545 mg/dL). Aripiprazole long-acting injection 400 mg monthly was combined with the ongoing clozapine treatment for augmentation. One week after the third injection, a psychiatric examination revealed a significant improvement in the positive symptoms, and his caregivers confirmed an increase in the social interaction of the patient. Although we cannot postulate on a single exact mechanism for the increased efficacy of clozapine and aripiprazole combination, we may suggest that, at least for a subgroup of patients with schizophrenia who respond clinically to clozapine at a suboptimal level, combination with aripiprazole may be an effective therapeutic strategy.