Patients with schizophrenia have a wide range of clinical responses to antipsychotic treatment, a typical experience among practicing psychiatrists. However, it was unclear whether this variance represents the variability of medication-specific effects (also known as “treatment effect heterogeneity”) or variability of non-specific effects such as spontaneous symptom fluctuation or placebo response.
Previous meta-analyses revealed little indication of treatment effect heterogeneity, indicating that a “one size fits all” strategy is suitable and that efforts to establish tailored treatment strategies for schizophrenia were unlikely to be successful. However, recent improvements suggest that prior methodologies may have been unable to assess treatment effect heterogeneity adequately due to a critical omission parameter: the association between placebo response and medication-specific effects. For a study, researchers addressed the problem by estimating that correlation and quantitatively characterizing antipsychotic treatment effect heterogeneity in schizophrenia using individual patient data and study-level data.
Individual patient data (on 384 people who got antipsychotic medication and 88 people who received a placebo) were gathered from the Yale University Open Data Access (YODA) database. In addition, a meta-analysis of 66 clinical trials including 17,202 people yielded study-level data. Individual patient and study-level analyses revealed a negative connection between placebo response and treatment impact on the Positive and Negative Syndrome Scale (PANSS) total score (ρ=–0.32, P=0.002 and ρ=–0.39, P<0.001, respectively). A meta-analysis of treatment effect heterogeneity using the most conservative of these estimates revealed marked variability in antipsychotic-specific effects among individuals with schizophrenia, with the top quartile of patients experiencing beneficial treatment effects of 17.7 points or more on the PANSS total score, while the bottom quartile experienced a detrimental effect of treatment relative to placebo. The evidence of clinically significant treatment effect heterogeneity implied that efforts to tailor antipsychotic therapy of schizophrenia may be successful.