IDENTIFICATION OF PREDICTORS FOR ANTIPSYCHOTIC-INDUCED WEIGHT GAIN: A NATIONWIDE COHORT STUDY
Authors: Ishikawa *Shuhei , Hashimoto Naoki , Okubo Ryo , Kusumi Ichiro 
Published: February 2025

Abstract

Background
Weight gain is a side effect of antipsychotic medications, and improved management remains an unmet need in the field (James Lind Alliance, 2011). Prevention and early intervention of antipsychotic-induced weight gain (AIWG) require an accurate prediction of its incidence. To predict AIWG incidence in clinical settings, assessing the effect of factors such as type, daily dose, and the number of antipsychotics is crucial, as well as concomitant medication type and background factors in naturalistic studies that consider facility characteristics. However, no studies have been conducted to predict its occurrence based on these assessments.

Aims And Objectives
This study aimed to identify the predictors of AIWG incidence by examining the effects of background- and medication-related factors on weight gain in patients with schizophrenia and bipolar disorder newly initiated on antipsychotic medication.

Methods
This was a nationwide, multicenter (24 general hospitals, 17 psychiatric hospitals, and 3 psychiatric clinics) prospective cohort study conducted in Japan. We recruited patients with schizophrenia, schizoaffective disorder, and bipolar disorder who were newly initiated on antipsychotic treatment. The primary endpoint was AIWG incidence (weight gain of 7% or greater) within the first 12 months after the initiation of antipsychotic treatment. We sought to identify the predictors of AIWG incidence in a multivariate analysis adjusting for background (including coexisting diagnoses, diet and exercise therapies, smoking and drinking habits, and duration of illness) and medication-related factors (type, daily dose, number of antipsychotic medication, and type of concomitant medication). We employed the Cox proportional hazards regression model, stratified by facility characteristics (university hospital, general hospitals, psychiatric hospitals, and psychiatric clinics).

Results
Among the 865 patients, 262 patients (30.3%) developed AIWG. Concerning medication-related factors, compared with the initiation of treatment with aripiprazole, the initiation of treatment with clozapine and olanzapine has a significantly higher AIWG incidence (hazard ratio [HR] = 2.17, 95% CI = 1.05–4.51; HR = 2.01, 95% CI = 1.36–2.96, respectively). Conversely, the initiation of treatment with blonanserin significantly decreased AIWG incidence (HR = 0.49, 95% CI = 0.24–0.98). In terms of antidepressants, the combination of trazodone (HR = 2.53, 95% CI = 1.17–5.50), selective serotonin reuptake inhibitor (HR = 2.30, 95% CI = 1.46–3.64), and mirtazapine (HR = 1.86, 95% CI = 1.04–3.34) significantly increased AIWG incidence. Regarding mood stabilizers, the combination of lithium carbonate and valproic acid (HR = 1.60, 95% CI = 1.01–2.53; HR = 1.53, 95% CI = 1.04–2.23, respectively) significantly increased AIWG incidence. Concerning background factors, outpatients and those receiving their first treatment had a higher AIWG incidence (HR = 1.75, 95% CI = 1.27–2.41; HR = 2.04, 95% CI = 1.38–3.02, respectively).

Discussion And Conclusion
The results of this study suggest that predicting AIWG incidence requires consideration not only of the type of newly initiated antipsychotic medication but also the type of concomitant medications (antidepressants and mood stabilizers) and patient treatment status.

References
1.James Lind Alliance (2011) Schizophrenia priority setting partnership. Available at: www.jla.nihr.ac.uk/priority-setting-partnerships/schizophrenia/top-10-priorities/ (accessed 13 September 2023).