Reduced Schizophrenia Maintenance Dose Improves Cognitive Function, Negative Symptoms

White pills and a bottle
White pills and a bottle
Investigators assessed the effect of a decrease in risperidone or olanzapine dosage on change in cognitive function and symptoms in stable patients with schizophrenia.

Reducing the dose of the antipsychotic medications olanzapine and risperidone during the maintenance treatment of stable patients with schizophrenia improves cognitive function and decreases negative symptoms without increasing the rate of relapse, according to a study published in the Journal of Psychopharmacology.

The question of whether the dose of antipsychotic treatment should be lowered during the maintenance stage of treatment vs the acute stage is controversial. Determining the appropriate medication levels to avoid relapse without leading to the movement disorders, metabolic syndrome, impaired cognitive function, and higher mortality rates associated with continued exposure to high doses of antipsychotic medications is crucial.

Using a 52-week, parallel group, single-blind, randomized controlled trial, the study investigators sought to examine symptomatology and cognitive function in stable patients with schizophrenia after a 50% reduction in dose of olanzapine and risperidone in the maintenance stage of treatment. Medication doses were not allowed to dip below the minimum recommended maintenance dosages (olanzapine 5 mg/d and risperidone 2 mg/d). In the first 4 weeks of the study, participants in the dose-reduction group had their doses of olanzapine and risperidone decreased by 25%. Doses were further decreased over the next 12 weeks to 50% of the original prescription. These participants were kept on the 50% reduced doses for the next 36 weeks (until the end of the study). Doses in the dose-maintenance group remained consistent throughout the 52 weeks of the study.

Results of the study determined that a 50% reduction in olanzapine and risperidone led to improved working memory, processing speed, and general cognitive functioning without increasing the rate of relapse. Dose reduction also led to an improvement in negative symptoms, as measured by the Positive and Negative Syndrome Scale and the 16-item version of the Negative Symptom Assessment. Cognitive function was measured using the current USDA standard: MATRICS Consensus Cognitive Battery.

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The limitations of the study include a sample size of only 75 subjects, the single-blind design, and the fact that the study involved treatment with olanzapine and risperidone only, so that the results do not necessarily apply to treatment with other antipsychotics.

The investigators feel that the study’s findings are sufficient to indicate the need for prescribers to “re-evaluate the treatment outcome when planning to use high doses of atypical antipsychotic drugs to prevent relapse during maintenance treatment. The present results suggested that such high-dose treatment strategies do not provide any superiority for managing psychotic symptoms, but can lead to more serious damage to the cognitive function of schizophrenic patients. Rather, careful dose reduction may help to improve negative symptoms and cognitive rehabilitation.”


Zhou Y, Li G, Li D, Cui H, Ning Y. Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: a single-blinded, 52-week, randomized controlled study [published online February 1, 2018]. J Psychopharmacol. doi: 10.1177/0269881118756062