T45. THE EFFICACY AND HETEROGENEITY OF ANTIPSYCHOTIC RESPONSE IN SCHIZOPHRENIA: A META-ANALYSIS

Abstract

BackgroundAntipsychotics are more effective than placebo in reducing symptoms in schizophrenia. However, response to treatment appears to vary, and as such it has been proposed that different subtypes of schizophrenia exist, defined by treatment-response. This has not been formally examined using meta-analysis.MethodsRandomised controlled trials comparing placebo and antipsychotics for the acute treatment of schizophrenia published between January 1 1950 and November 30, 2018 were examined. Mean change and variance of change in symptoms were extracted from each study, alongside publication year, participant age and gender, baseline symptom severity, antipsychotic dose, and use of placebo lead-in. Relative variability of symptomatic improvement in antipsychotic-treated individuals compared to placebo-treated individuals was quantified using coefficient of variation ratio (CVR). Mean difference in symptom change was quantified using Hedges’ g. The significance of potential moderating factors was assessed using meta-regression and sensitivity analyses. In addition, individual patient data from two clinical trials (N=522) was examined in terms of both the distribution of total symptom change, and the variability of individual symptoms and symptom factors.Results11,006 articles were identified. 66 met inclusion criteria, reporting on 17,202 participants. Compared with placebo, antipsychotic-treated patients demonstrated both greater symptomatic improvement (g=0.47, p<0.001) and reduced variability in symptomatic improvement (CVR=0.86, p<0.001). Lower variability in antipsychotic-response was associated with studies including younger patients (z=3.07, p=0.002), those published earlier (z=3.98, p<0.001), with higher dose treatments (z=-2.62, p=0.009), and greater mean-difference in symptom-change (z=-5.70, p<0.001). In the individual patient data antipsychotic treated patients did not show significantly increased variability for any individual symptom, and there was no evidence of a bimodal distribution of response.DiscussionCompared to placebo, in addition to a greater mean change, antipsychotic treatment shows lower variability of change in total, positive, and negative symptoms. This is contrary to the hypothesis that there exists a subtype of antipsychotic non-responsive schizophrenia, instead providing evidence for a relatively homogeneous effect of antipsychotic treatment in improving symptoms of schizophrenia.