VARIATION IN SIDE EFFECTS TO ANTIPSYCHOTIC TREATMENT ACROSS SCHIZOPHRENIA SPECTRUM DISORDERS

Abstract Background Adverse effects of antipsychotic drugs play a key role in non-compliance and discontinuation of treatment in Schizophrenia Spectrum Disorders (SSD). Precision medicine aims to minimize such adverse effects by selecting the right treatment for the right patients. To determine the need for precision medicine we need to estimate the amount of variation in adverse effects between patients. While clinical experience suggests that such variation is considerable, analyzing how variation differs between treated and untreated patients can answer this question. Here, we hypothesized to find larger variation in treatment compared to control groups of patients treated with second generation antipsychotics. Methods We included double-blind, placebo-controlled, randomized trials of adults with a diagnosis of schizophrenia spectrum disorders and prescription for licensed antipsychotic drugs. Means and variances of the pretreatment and posttreatment outcome differences of weight gain, prolactine levels, and corrected QTC times were extracted. Data quality and validity were ensured by following the PRISMA guidelines. The outcome measure was the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. Results We included N = 13 282 patients for weight gain, N = 11 767 for prolactine levels, and N = 7 203 for QTC time. For all the measured adverse effects, variances were greater in treatment compared to control. Specifically, variance ratios were increased for weight gain (VR = 1.13, 95% CI: 1.06, 1.20), prolactine levels (VR = 1.38, 95% CI: 1.13, 1.68) and QTc time (VR = 1.06, 95% CI: 1.01, 1.12). Discussion We found increased variability in the major side effects that patients with SSD had under treatment with second generation antipsychotics. Indeed, some patients were more susceptible than others to weight gain, prolactine level increase, and QTC time increase, suggesting that precision medicine in antipsychotic treatment should be informed by individual differences in side effects rather than treatment effects. Future studies should aim at finding biological predictors of such individual differences in side effects.