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

Medical Hypotheses
Ric M ProcyshynAlasdair M Barr

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.

References

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Citations

Dec 3, 2015·Psychopharmacology·Christoffer Polcwiartek, Jimmi Nielsen
Feb 5, 2015·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Hiroyoshi TakeuchiGary Remington
May 18, 2016·Acta Psychiatrica Scandinavica·H TakeuchiG Remington
Mar 13, 2014·The Annals of Pharmacotherapy·Jonathan G LeungJessica L Gören
Oct 28, 2019·Therapeutic Drug Monitoring·Ebenezer OloyedeDavid Taylor
Apr 20, 2018·Frontiers in Neuroscience·Jessica W Y YuenAlasdair M Barr
Feb 16, 2021·Journal of Clinical Psychopharmacology·Georgios SchoretsanitisJose de Leon
Mar 23, 2021·Schizophrenia Bulletin·Hiroyoshi TakeuchiGary Remington
Apr 15, 2020·Psychotherapy and Psychosomatics·Jose de LeonCarlos De Las Cuevas

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