"Extended" Antipsychotic Dosing in the Maintenance Treatment of Schizophrenia: A Double-Blind, Placebo-Controlled Trial

Objective: In the treatment of schizophrenia, all currently available oral antipsychotics are administered at least once daily, with strict adherence strongly encouraged to minimize risk of relapse. Based on a better understanding of the brain kinetics of antipsychotics, we have proposed a variation of this approach, "extended" dosing, which allows for intermittent but regular dosing.

Method: We carried out a randomized, double-blind, placebo-controlled trial evaluating 35 individuals with DSM-IV-defined schizophrenia who had been stabilized on antipsychotic therapy. Over a 6-month interval, 18 subjects received their medication as usual (daily), while 17 received their antipsychotic therapy every second day (extended). Outcome measures included clinical scales to assess symptoms (Brief Psychiatric Rating Scale [the primary outcome measure], Calgary Depression Scale), illness severity (Clinical Global Impressions-Severity of Illness scale), and relapse (ie, rehospitalization) rates. Side effects were also assessed, including movement disorders (Barnes Akathisia Scale, Simpson-Angus Scale, Abnormal Involuntary Movement Scale) and weight. The study was conducted from February 2003 to July 2007.

Results: Individuals in the extended dosing group were not at greater risk of symptom exacerbation, relapse, or rehospitalization; indeed, more rehospitalizations occurred in those receiving regular dosing. At the same time, though, there was no indication that side effects were significantly reduced in the extended dosing group.

Conclusions: These results challenge the long-standing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia. Further studies with larger samples are needed to replicate these findings, as well as to elucidate whether postulated clinical advantages can be established and determined to outweigh potential risks.

Trial Registration: clinicaltrials.gov Identifier: NCT00431574

J Clin Psychiatry 2011;72(8):1042-1048

Submitted: November 29, 2009; accepted March 10, 2010.

Online ahead of print: September 7, 2010 (doi:10.4088/JCP.09m05866yel).

Corresponding author: Gary Remington, MD, Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada (gary_remington@camh.net).