Low Dose vs Standard Dose of Antipsychotics for Relapse Prevention in Schizophrenia


Hiroyuki Uchida; Takefumi Suzuki; Hiroyoshi Takeuchi; Tamara Arenovich; David C. Mamo


Schizophr Bull. 2011;37(4):788-799. 

In This Article

Abstract and Introduction


Background: It remains unknown as to whether the antipsychotic dose needed for the acute-phase treatment of schizophrenia is also necessary for relapse prevention.
Aim: To compare the efficacy between standard dose [(World Health Organization daily defined dose (DDD)] vs low dose (≥50% to <1 DDD) or very low dose (<50% DDD) for relapse prevention in schizophrenia.
Data source: Double-blind, randomized, controlled trials with a follow-up duration of ≥24 weeks, including ≥2 dosage groups of the same antipsychotic drug for relapse prevention in schizophrenia, were searched using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE (last search: August 2009).
Data extraction: Data on overall treatment failure, hospitalization, relapse, and dropouts due to side effects were extracted and combined in a meta-analysis.
Data synthesis: Thirteen studies with 1395 subjects were included in this meta-analysis. Compared with the standard-dose treatment, the low-dose therapy did not show any statistically significant difference in overall treatment failure or hospitalization, while the standard dose showed a trend-level (P = .05) superiority in risk of relapse. The very low–dose group was inferior to the standard-dose group in all efficacy parameters. No significant difference was found in the rate of dropouts due to side effects between either standard dose vs low dose or very low dose.
Conclusions: Although antipsychotic treatment with ≥50% to <1 DDD may be as effective as standard-dose therapy, there are insufficient clinical trial data to draw firm conclusions on standard- vs low-dose maintenance antipsychotic therapy for schizophrenia.


Antipsychotic drugs have played a central role in the treatment of schizophrenia for more than 50 years.[1] Antipsychotic treatment significantly reduces the risk of relapse; however, this also causes various side effects, including motor, metabolic, and cardiovascular side effects,[2–5] which contributes to poor adherence and undesirable outcome.[6] Given that the risk for these adverse effects from antipsychotic drugs is often dose-related,[2,4,5] the use of the lowest possible effective antipsychotic dose for relapse prevention is critically important to enhance the overall treatment outcome. While dosing issues of antipsychotic treatment to relieve acute psychotic symptoms of schizophrenia have been widely investigated,[7,8] data are still limited on the therapeutic dose for relapse prevention. One clinically important question remains unanswered: "Is the dose needed for the acute phase also necessary for relapse prevention?" In fact, major treatment guidelines suggest opposite treatment strategies.[9–11] For example, the practice guidelines by the American Psychiatric Association (APA) recommend the use of the lowest possible effective dose for the maintenance treatment,[9] while the Expert Consensus Guidelines generally advocate the continuous use of antipsychotic dose that was effective in the acute phase also for relapse prevention.[10] To address this gap in knowledge, we conducted a meta-analysis to compare the efficacy and safety of standard dose (ie, equal to or more than the defined daily dose [DDD] by the World Health Organization) vs low dose (ie, less than the defined dose, but equal to or greater than half the dose) or very low dose (ie, less than half the defined dose) for relapse prevention in the treatment of schizophrenia or schizoaffective disorder.


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