Antipsychotic Treatment and Longitudinal Body Mass Index Trajectories in Youth with and Without Autism Spectrum Disorder

<b>Background:</b> Children and adolescents with autism spectrum disorder (ASD) frequently receive antipsychotics and are considered at increased risk for weight gain. Few studies have compared longitudinal weight trajectories between youth with ASD and those with other psychiatric disorders. <b>Methods:</b> This naturalistic, registry-based study used data from the SENTIA cohort, which prospectively monitors antipsychotic safety in individuals under 18 years at a university hospital in Spain. Clinical characteristics were compared between participants with and without ASD. Longitudinal body mass index (BMI) z-score trajectories were analysed using linear mixed-effects models. <b>Results:</b> The sample included 266 participants, of whom 113 (42.5%) had ASD. Individuals with ASD were more often male and initiated antipsychotic treatment at a younger age. Of the 26 participants prescribed an antipsychotic before age 6, 88.5% had ASD. Comorbidity profiles were similar across groups. Risperidone and aripiprazole were the most frequently prescribed antipsychotics. BMI z-scores increased over time (β = 0.130, <i>p</i> = 0.017), and baseline BMI z-score was the strongest predictor. ASD diagnosis did not modify the average linear rate of BMI z-score change (time × ASD: <i>p</i> = 0.251); however, a significant quadratic time × ASD interaction (β = -0.016, <i>p</i> = 0.041) was consistent with a more pronounced early increase followed by earlier attenuation of BMI z-scores in the ASD group. <b>Conclusions:</b> Although antipsychotic treatment was initiated earlier in youth with ASD, no clear difference was observed in the rate of BMI z-score change. Differences in weight trajectories underscore the need for metabolic monitoring in antipsychotic-treated youth.