Does Concomitant Psychostimulants Mitigate Second-Generation Antipsychotics-Associated Weight Gain? An Observational Study Based on Electronic Medical Records Data

<b><i>Objective:</i></b> Weight loss is a well-documented adverse effect of psychostimulants. Given their frequent coprescription with second-generation antipsychotics (SGA) in pediatric patients, this study aims to examine whether concomitant use of psychostimulants mitigates SGA-associated weight gain in children and adolescents. <b><i>Method:</i></b> This study utilized the IQVIA Ambulatory electronic medical record-U.S. database (2016-2021) to identify patients aged 6-17 years who initiated an SGA. Those who started psychostimulants within 7 days of SGA initiation and maintained ≥90 days of use were classified as concomitant users, while those who initiated psychostimulants later with ≥90 days of overlap were add-on users. Patients never prescribed psychostimulants were SGA-only users. After adjusting for the baseline covariates using propensity scores, 6- and 12-month body mass index (BMI) <i>z</i>-score trends following psychostimulant initiation were compared between (1) concomitant and SGA-only users and (2) add-on and SGA-only users, using a linear mixed-effects regression model. <b><i>Results:</i></b> The results of linear mixed effect regression models indicate that concomitant users experienced a 0.0143 less monthly BMI <i>z</i>-score increase (<i>p</i> = 0.0063) compared with the SGA-only users over the 6 months following psychostimulant initiation. Similarly, add-on users had a significantly lower rate of weight gain compared with SGA-only users (<i>β</i> = -0.0463, <i>p</i> < 0.0001). When the follow-up period was extended to 12 months, the sensitivity analyses for both concomitant and add-on users were consistent with their primary analyses. <b><i>Conclusions:</i></b> Concomitant and add-on psychostimulants appear to mitigate SGA-associated weight gain in children and adolescents. Further investigation is needed to understand their effectiveness and safety relative to other interventions for antipsychotic-associated weight gain.