Clozapine administered once versus twice daily: does it make a difference?

Med Hypotheses. 2014 Feb;82(2):225-8. doi: 10.1016/j.mehy.2013.11.043. Epub 2013 Dec 9.

Abstract

Clozapine, generally considered to be the most effective antipsychotic, is the gold standard for treatment-resistant schizophrenia. With a relatively short half-life of 12h and a very quick dissociation rate from the dopamine D2 receptor, pharmacokinetic and pharmacodynamics principles would dictate that clozapine be administered twice daily. However, due to clozapine's side effects (e.g., sedation), it is often prescribe once daily at bedtime. Even if the patient develops tolerance to the side effects, it is still often prescribed once daily to simplify medication regimens in hopes of increasing adherence. Unfortunately, good intentions and convenience do not always make for optimal pharmacotherapy. Based upon clozapine's pharmacokinetic and pharmacodynamic profiles, we hypothesize that optimal treatment with clozapine requires it be given twice daily rather than once daily. We present here some pharmacokinetic simulations and published data to support our hypothesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / pharmacokinetics
  • Clozapine / administration & dosage*
  • Clozapine / pharmacokinetics
  • Drug Administration Schedule*
  • Drug Monitoring / methods
  • Humans
  • Models, Theoretical
  • Patient Compliance
  • Receptors, Dopamine D2 / metabolism
  • Schizophrenia / drug therapy*
  • Time Factors

Substances

  • Antipsychotic Agents
  • Receptors, Dopamine D2
  • Clozapine