Effects of risperidone and olanzapine dose reduction on cognitive function in stable patients with schizophrenia: an open-label, randomized, controlled, pilot study

Schizophr Bull. 2013 Sep;39(5):993-8. doi: 10.1093/schbul/sbt090. Epub 2013 Jul 1.


Impact of dose reduction of atypical antipsychotics on cognitive function has not been investigated in stable patients with schizophrenia. In this open-label, 28-week, randomized controlled trial, stable patients with schizophrenia treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50% in 4 weeks and then maintained) or maintenance group (dose kept constant). Assessments at baseline and week 28 included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Sixty-one patients were enrolled; 2 of 31 (6.5%) and 5 of 30 (16.7%) patients prematurely withdrew from the study in the reduction and maintenance groups, respectively. While no significant differences in change in the PANSS total score were observed between the 2 groups, the reduction group showed significantly greater improvements in the RBANS and DIEPSS total scores compared with the maintenance group (mean ± SD, +7.0±7.1 vs -0.1±8.0, P < .001; -0.9±1.7 vs +0.1±1.2, P = .010, respectively). This 6-month pilot study suggests that risperidone or olanzapine dose reduction of 50% can improve cognitive function for stable patients with schizophrenia. Due to the open-label design, small sample size, and short study duration, however, there is a need to confirm the finding through double-blind, larger scale trials with longer follow-up periods. Moreover, potential risks of relapse following antipsychotic dose reduction should be thoroughly investigated in longer term studies.

Keywords: antipsychotics; cognitive function; dose reduction; olanzapine; risperidone; schizophrenia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents* / administration & dosage
  • Antipsychotic Agents* / pharmacology
  • Benzodiazepines* / administration & dosage
  • Benzodiazepines* / pharmacology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Drug Administration Schedule
  • Female
  • Humans
  • Maintenance Chemotherapy / methods
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Olanzapine
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Risperidone* / administration & dosage
  • Risperidone* / pharmacology
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Treatment Outcome


  • Antipsychotic Agents
  • Benzodiazepines
  • Risperidone
  • Olanzapine