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

Andrea Bellavia, Franca Centorrino, John W. Jackson, Garrett Fitzmaurice, Linda Valeri

Research output: Contribution to journalArticlepeer-review

Abstract

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 months, separately evaluated as positive (PANSS+), negative (PANSS−), and total PANSS score. WG after 6 months 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.

Original languageEnglish (US)
Pages (from-to)96-102
Number of pages7
JournalSchizophrenia Research
Volume206
DOIs
StatePublished - Apr 2019

Keywords

  • Antipsychotics
  • Interaction
  • Mediation
  • PANSS score
  • Weight gain

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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