Time to treatment response in first-episode schizophrenia: should acute treatment trials last several months?

Response patterns may differ between patients with first-episode and multiepisode schizophrenia. This analysis explored trial duration with first-episode patients and asked whether early limited improvement predicts ultimate lack of treatment response with first-episode patients as it does with multiepisode patients.

One hundred twelve subjects (mean age = 23.3 years, SD = 5.1 years) who presented between November 1998 and October 2004 with a first episode of psychosis and had a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were randomly assigned to treatment with olanzapine or risperidone for 16 weeks. Treatment response, the primary outcome measure, was defined as a rating of mild or better on all of the positive symptom items on the Schedule for Affective Disorders and Schizophrenia Change Version With Psychosis and Disorganization Items. Response rates were calculated for each study week. A logistic regression analysis examined the association between percentage reduction in symptom severity scores from baseline values at weeks 2, 4, or 8 and response by week 16. The study was conducted at The Zucker Hillside Hospital, Glen Oaks, New York and the Bronx-Lebanon Hospital Center, Bronx, New York.

The estimated cumulative response rate was 39.59% (95% CI, 29.77%-49.41%) by week 8 and 65.19% (95% CI, 55.11%-75.27%) by week 16. The confidence intervals for estimated response at weeks 10, 12, 14, and 16 were not distinct. Response rates increased approximately 5 to 6 percentage points each 2-week interval between week 10 and 16. Percentage reduction in symptom severity score at week 4 (but not 2 or 8) was associated (χ²₁ = 3.96; P < .05) with responder status at week 16 (odds ratio = 1.03; 95% CI, 1.00-1.05). However, receiver operating characteristic curves did not suggest any level of percentage symptom reduction that would be clinically useful as a predictor of response by week 16.

Many first-episode patients respond between weeks 8 and 16 of treatment with a single antipsychotic medication. Limited early symptom improvement does not identify those first-episode patients who will not improve with a full 16-week trial with enough accuracy to be clinically useful.

clinicaltrials.gov Identifier: NCT00000374.