Review of: Zhou Y et al, Journal of Psychopharmacology 2018. doi:10.1177/0269881118756062

Once patients with schizophrenia are stabilized on an antipsychotic in the acute phase of their treatment, guidelines are unclear on how to continue dosing. Some guidelines recommend lowering the dose, others recommend maintaining the dose, and others give no firm recommendations whatsoever.

For fear of relapse, many clinicians never lower the dose, so many patients are simply kept on the higher acute-phase doses. These doses can be associated with more side effects, including extrapyramidal symptoms, metabolic syndrome, and impaired cognitive function.

This 52-week, single-blinded (rater-blinded), randomized controlled study sought data on maintenance and reduction using 2 frequently prescribed antipsychotics. Relapse was defined as a score of ≥ 4 on the Positive and Negative Syndrome Scale (PANSS) on at least one of the following: delusion, conceptual disorganization, hallucinatory behavior, or suspiciousness.

Researchers studied 75 stabilized schizophrenic patients, who were prescribed either risperidone (≥ 4 mg/day) or olanzapine (≥ 10 mg/day). They were randomly divided into a maintenance group (n = 38) and a dose-reduction group (n = 37).

In the maintenance group, the dose of medication remained unchanged. In the dose-reduction group, the dose of antipsychotic was reduced by 25% for the first 4 weeks, then reduced by 50% of the original dose for the remaining 48 weeks. Doses were never lowered below minimum recommendations—ie, below 2 mg/day for risperidone or below 5 mg/day for olanzapine.

Over 52 weeks, relapse rates were not significantly different between the groups, with relapse of only 4 patients in the dose-reduction group and 6 patients in the maintenance group.

A 50% dose reduction of antipsychotics did not lead to any worsening of psychotic symptoms. In fact, patients on the lower doses had fewer extrapyramidal symptoms (p = 0.012), lower body mass index (p = 0.005), improved cognitive function (p = 0.001), and improved negative symptoms overall (p < 0.001).

TCPR’s Take
Despite a small sample size, using single rather than double blinding, and being limited to only 2 antipsychotics, this study offers much-needed evidence to guide some important clinical decisions. During the maintenance phase with our stabilized schizophrenic patients, careful antipsychotic dose reduction (by 25% over the first 4 weeks, and then by 50% thereafter) is worth trying.