1. In this study, both individual patient and study-level analyses revealed a negative correlation between placebo response and treatment effect, as measured with the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity in schizophrenia patients.

2. Furthermore, treatment effect heterogeneity showed variation in antipsychotic-specific effects among individuals with schizophrenia.

 Evidence Rating Level: 1 (Excellent)

Individuals with schizophrenia have a broad range of symptomatic responses to antipsychotic treatment, as commonly observed by practicing psychiatrists. Given the possible benefits of tailoring treatment optimized to the patients, quantifying treatment effect heterogeneity (defined as variations in medication-specific effects) in schizophrenia is critical. Specifically, it is important to further elucidate the relationship between treatment effect and placebo response. In the absence of this characteristic, an increasing corpus of literature cannot be accurately interpreted.

The present study estimated this correlation using individual patient data and study-level treatment effects from clinical trials, which were applied to a variability meta-analysis to formally estimate the heterogeneity of antipsychotic effects amongst schizophrenia patients.  Individual patient data from adult patients aged 18-65 years old receiving antipsychotic therapy (n=384) or placebo (n=88) were included from The Yale University Open Data Access database. Study-level data of schizophrenia patients aged 18-65 years old were included in a meta-analysis of 66 clinical trials (n=17,202). Study outcomes analyzed symptom severity in schizophrenia patients using the PANSS.

Study results demonstrated that in both individual patient and study-level analysis, there was a negative correlation between placebo response and treatment effect. Furthermore, a meta-analysis of treatment effect heterogeneity using the most conservative of these estimates revealed variation in antipsychotic-specific effects among individuals with schizophrenia. Notably, the top quartile of individuals experienced healthy treatment effects of 17.7 points or better on the PANSS total score, whereas the bottom quartile had a treatment effect worse than placebo. However, this study was limited by a correlation detected across research at the study level that may not reflect correlation at the person level, which is known as aggregation bias. Nonetheless, this study was significant in supporting the notion that in schizophrenia, there is significant interindividual variation in terms of symptomatic response to antipsychotic treatment.

Click to read study in: World Psychiatry

Image: PD

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