Early Response to Antipsychotic Drug Therapy as a Clinical Marker of Subsequent Response in the Treatment of Schizophrenia

Abstract

Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether 'switching' early non-responders to another antipsychotic is a better strategy than 'staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as X20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2-6 mg/day or switch to olanzapine 10-20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; po001). Early response/nonresponse was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p ¼ 0.020) and in depressive symptoms (end point; p ¼ 0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatmentemergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a 'switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.

The Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) Trial: Rationale for Its Methodology and a Review of the Effectiveness of Switching Antipsychotics

“…The outcome of the switchers was slightly, but statistically significantly (P = .02) better than that of the stayers, and the difference was more pronounced in patients who were at least moderately ill at week 2. 30 In any case the early improvers at 2 weeks had a clearly better outcome than the early nonimprovers, irrespectively of the subsequently assigned treatment of the latter.…”

“…Strongest support that switching nonresponders to a different drug is effective, stems from a recent large trial in which 628 mainly chronic patients with schizophrenia or schizoaffective disorder were treated for 2 weeks with flexibly dosed risperidone (2-6 mg/d, Kinon et al 30 ). Those who had not shown at least a 20% reduction of the PANSS were randomized to double-blind treatment with either continuation of risperidone or a switch to olanzapine (10-20 mg/d) for an additional 10 weeks.…”

Early Antipsychotic Response Predictors in Schizophrenia: A Naturalistic Study

“…On the other hand, in the last years it was repeatedly demonstrated that early antipsychotic response is a strong predictor of subsequent response [14][15][16][17][18][19][20][21]. We therefore hypothesized that ER patients could represent a distinct subgroup of patients, identified by specific clinical and demographic characteristics.…”

“…According to the "early onset hypothesis" of antipsychotic action, an increasing number of studies showed that the early response to antipsychotics is a very robust predictor of longterm outcome [14][15][16][17][18][19][20][21]. Early response is defined in different manners by different Authors.…”

Pharmacogenetics of Schizophrenia: Bringing ‘Order to Chaos' in the Psychopharmacology of Schizophrenia?

“…Antipsychotic efficacy appears to be tied -at least to some extent -to dopamine (D 2 ) blockade. Recent enthusiasm that glutamate alone might be a distinct target has been dampened by the results of a recent trial of a glutamatergic drug that had shown initial promise [10] . Additionally, these drugs have highly variable pharmacologic profiles at several other neuroreceptors.…”