Pharmacokinetics of the Long‐Acting, First‐Generation Antipsychotic Fluphenazine

Abstract

Despite the advantages of second‐generation antipsychotics, effectiveness trials and cost‐effective analyses have caused first‐generation antipsychotics to be reexamined with regard to place in therapy. Developing an understanding of all aspects of first‐generation antipsychotics, including the pharmacokinetic complexity of long‐acting decanoate formulations, are essential for practitioners in order to optimally manage both symptoms and adverse events. We describe a 55‐year‐old schizophrenic man with a severe movement disorder whose symptoms were mistaken for lithium toxicity. Further examination revealed that his fluphenazine plasma level was still detected 4 months after his last dose of fluphenazine decanoate had been administered. The incorrect diagnosis of lithium toxicity resulted in delayed treatment of his severe extrapyramidal symptoms. Administration of a routine dosage of benztropine titrated to 4 mg/day resolved his drug‐induced movement disorder within 72 hours. This case report demonstrates the persistent need for practitioners' awareness of the complex pharmacokinetic properties of long‐term fluphenazine decanoate treatment, resulting in prolonged absorption, and the continued importance of both recognizing adverse events resulting from dopamine D2‐receptor antagonism and developing the ability to distinguish between various types of movement disorders. The potential for increasing use of first‐generation antipsychotics highlights the need to revisit the nuances of long‐acting, injectable pharmacokinetics to improve patient outcomes.