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

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. © 2011 Pharmacotherapy Publications Inc.