Schizophrenia Research | 2019

The role of weight gain in explaining the effects of antipsychotic drugs on positive and negative symptoms: An analysis of the CATIE schizophrenia trial



Second-generation antipsychotics are associated with moderate benefits in terms of improved schizophrenia symptoms, but also with higher rates of side-effects such as excessive weight gain (WG); a consensus on their efficacy has not been reached. To date, no study has evaluated the interplay of treatments and side-effects in a single framework, which is a critical step to clarify the role of side-effects in explaining the efficacy of these antipsychotics. We used recent methods for mediation and interaction to clarify the role of WG in explaining the effects of second-generation drugs on schizophrenia symptoms. We used data from 1460 participants in the CATIE trial, assigned to either perphenazine (first-generation comparison drug), olanzapine, quetiapine, risperidone, or ziprasidone. The primary outcome was an individual s score on the Positive and Negative Syndrome Scale (PANSS) for symptoms of schizophrenia after 9\u202fmonths, separately evaluated as positive (PANSS+), negative (PANSS-), and total PANSS score. WG after 6\xa0months was investigated as a potential mediator and effect modifier. Results showed that, by limiting WG, patients would benefit of a considerably better improvement in terms of PANSS symptoms. In the scenario of weight change being controlled between -2% and 1% for all participants, patients assigned to olanzapine would experience the highest significant improvements in both PANSS+ (-2.66 points; 95% CI: -4.98, -0.35), PANSS- (-1.59; 95% CI: -4.31, 1.14), and total PANSS (-6.11; 95% CI: -13.13, 0.92). In conclusion, occurrence of excessive WG hampers the potentially beneficial effects of second-generation antipsychotics, thus suggesting future directions for treatment and interventions.

Volume 206
Pages 96-102
DOI 10.1016/j.schres.2018.12.006
Language English
Journal Schizophrenia Research

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