title: Clozapine administered once versus twice daily: does it make a difference?
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.
authors.affiliation: British Columbia Mental Health and Addictions Research Institute, 938 W 28th Avenue, Vancouver, B.C. V5Z 4H4, Canada; Department of Psychiatry, University of British Columbia, Vancouver V6T 1Z3, Canada. Electronic address: rprocyshyn@bcmhs.bc.ca.
authors.forename: Ric M
authors.initials: RM
authors.lastname: Procyshyn
authors.affiliation: British Columbia Mental Health and Addictions Research Institute, 938 W 28th Avenue, Vancouver, B.C. V5Z 4H4, Canada; Department of Psychiatry, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: Fidel
authors.initials: F
authors.lastname: Vila-Rodriguez
authors.affiliation: British Columbia Mental Health and Addictions Research Institute, 938 W 28th Avenue, Vancouver, B.C. V5Z 4H4, Canada; Department of Psychiatry, University of British Columbia, Vancouver V6T 1Z3, Canada.
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.affiliation: British Columbia Mental Health and Addictions Research Institute, 938 W 28th Avenue, Vancouver, B.C. V5Z 4H4, Canada; Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Barr
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003024:Clozapine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008962:Models, Theoretical; D010349:Patient Compliance; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D003024:Clozapine