Early non-response is a predictor of later non-response to antipsychotics in schizophrenia

1. For patients with schizophrenia, symptomatic response to antipsychotic medication at 2 and 4 weeks after initiation can appropriately predict non-response at 8 weeks, varying by baseline severity and specific antipsychotic trialed.

Evidence Rating Level: 1 (Excellent)

For patients with schizophrenia trialed on antipsychotic medication, it is unclear when to switch medication for failed responses, with guidelines ranging from 2-8 weeks. Though a meta-analysis suggested that non-improvement after 2 weeks of an antipsychotic trial was predictive of future non-improvement, baseline severity of schizophrenia was not accounted for. This is important as higher baseline severity tends to be associated with increased symptom reduction if responsive to antipsychotics. The specific medication can also influence when a response can typically be expected. Therefore, this multicentre clinical trial aimed to evaluate whether non-response to antipsychotics after week 2 or 4 could accurately predict non-response at week 8, for patients randomized to the antipsychotics olanzapine, risperidone, amisulpride, and aripiprazole. The study population included adult patients diagnosed with schizophrenia with symptoms for less than 5 years, stratified by baseline severity. Patients were evaluated with the positive and negative syndrome scale (PANSS), at baseline and weeks 2, 4, and 8. A reduction in PANSS of less than 20% between baseline and week 8 was considered to be a non-response. In total, there were 964 patients included, with a mean (SD) baseline PANSS of 84.52 (19.20). The study found for the severe and mild schizophrenia patients, a PANSS reduction less than 5% at 2 weeks was most accurate for predicting non-response at 8 weeks (total accuracy 75.0%, for severe, 80.8% for mild). For moderate schizophrenia at 2 weeks, a reduction of less than 10% showed the highest accuracy of 84.0%. For olanzapine and aripiprazole, a reduction of less than 10% at week 2 was most accurate (79.2% and 77.4% respectively), whereas for risperidone and amisulpride, a reduction of less than 5% was most accurate (82.4% and 78.2% respectively). At week 4, a PANSS reduction of less than 20% best-predicted non-response for all severities of illness (accuracy 91.0%, 89.8%, and 92.1% for severe, moderate, and mild respectively) and for all antipsychotics (accuracy 90.9%, 90.7%, 90.4%, and 90.8% for olanzapine, risperidone, amisulpride, and aripiprazole respectively). Overall, this study demonstrated that symptom reduction at 2 and 4 weeks after starting an antipsychotic can reasonably predict non-response at 8 weeks, depending on baseline severity and medication.

Click to read the study in BMC Medicine

Image: PD

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