"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.


METHODS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00431574.
Remington
Gary
G
Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada gary_remington@camh.net
Seeman
Philip
P
Feingold
Alan
A
Mann
Steve
S
Shammi
Chekkera
C
Kapur
Shitij
S
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects; D010054:Brief Psychiatric Rating Scale; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008152:Loxapine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D009864:Ontario; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D055502:Secondary Prevention
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D008152:Loxapine; D000077152:Olanzapine