The heterogeneity of antipsychotic response in the treatment of schizophrenia

Abstract

BackgroundSchizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response.MethodGrowth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine.ResultsFour distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified.ConclusionsThis study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.

Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis

“…However, not having a schizophrenia diagnosis , good pre-morbid and cognitive functioning ) and female gender have been associated with better response trajectories, whereas dropping out of the study has been associated with trajectories of worse response (Levine & Leucht, 2010;. Factors such as age at psychosis onset and initial symptom severity have shown contradictory results in previous studies (Levine & Leucht, 2010;Case et al 2011;Stauffer et al 2011). Discrepancies in results may also be explained by the use of chronic samples by previous studies.…”

Increased Resting-State Gamma-Band Connectivity in First-Episode Schizophrenia

“…49 Because participation in the original project included 3 to 5 neurophysiological testing sessions (EEG, MEG and EEG/fMRI), it was not always possible to conduct clinical assessments close to the EEG session. Therefore, based on reported trajectories of antipsychotic treatment response, 50,51 clinical severity ratings were used for analyses only if they were separated from EEG analyses by no more than a week for acutely ill patients, or 2 months for stable patients (ie, those with no change in medication for at least 2 months prior to study participation). Appropriate clinical ratings were available for 19 patients.…”

The use of clinical and biological characteristics to predict outcome following First Episode Psychosis

“…Using Growth Mixture Modeling (GMM) for Positive and Negative Symptom Scores (PANSS) in the first 12 weeks of treatment for FEP, Case et al (2011) were able to identify four distinct patterns of early treatment response to olanzapine or risperidone. Rapid response to treatment strongly correlated with the ultimate, longer-term treatment success.…”