CNP Paul Janssen Awards(PJ)

  1. CNP Paul Janssen Awards(PJ)
  2. Prize for Encouragement of the society(EN)

PJ-1

Increasing Versus Maintaining the Dose of Olanzapine or Risperidone for Schizophrenia Patients Who Did Not Respond to Modest Dosage:A Double-Blind Randomized Controlled Trial

Hitoshi Sakurai1,2, Takefumi Suzuki1,2, Robert R. Bies3,4, Bruce G. Pollock4,5, Masaru Mimura1, Shitij Kapur6, Hiroyuki Uchida1,4

  1. Department of Neuropsychiatry, Keio University School of Medicine
  2. Inokashira Hospital
  3. Division of Clinical Pharmacology, Indiana University School of Medicine
  4. Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto
  5. Department of Psychiatry, University of Toronto
  6. Department of Psychosis Studies, Institute of Psychiatry, King’s College, London

Objective: While doctors often increase the dose of an antipsychotic when there is insufficient response; there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. Method: In this four-week double-blind randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia ( ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to the dose increment or continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks whereas in the continuation group doses were not changed. Completion rate, changes in psychopathology, function, and extrapyramidal symptoms, and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined. Results: The completion rate was significantly lower in the increment group than the continuation group ( 69.2% [36/52] vs. 86.3% [44/51], p=0.038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group. Those with lower plasma concentrations of olanzapine on their initial treatment, showed a greater improvement in the Positive and Negative Syndrome Scale ( PANSS) positive subscale when their dose was increased ( p=0.042). Conclusions: As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from increasing the dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out.

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  1. CNP Paul Janssen Awards(PJ)
  2. Prize for Encouragement of the society(EN)