Comparative BMI-z Changes With Initiation and Adherence to Antidepressant Medications Among Youth

To estimate effects of initiating and subsequently adhering to different antidepressant medications on average BMI-z (a standardized measure of BMI relative to peers of the same age and sex) changes among youth by emulating a target trial.

We analyzed electronic health records (2010-2019) from 11 US health care systems, including 67,039 patients aged 5 to <19.5 years. Using prescription data, we assessed initiation and adherence to sertraline, fluoxetine, escitalopram, citalopram, or bupropion. The primary outcome was mean 12-month BMI-z change; the secondary outcome was 6-month change. We applied inverse probability weighting of marginal structural models to estimate population-level effects, adjusting for baseline and time-varying covariates. We estimated both absolute and sertraline-relative BMI-z changes. Secondary analyses evaluated effects of medication initiation alone, regardless of adherence.

At 12 months, we estimated a mean BMI-z gain of 0.10 units (95% CI = 0.02, 0.16) for sertraline, 0.18 (95% CI = 0.01, 0.32) for citalopram, 0.18 (95% CI = 0.07, 0.27) for escitalopram, 0.18 (95% CI = 0.11, 0.23) for fluoxetine, and -0.06 (95% CI = -0.23, 0.09) for bupropion, had all patients initiated and adhered to these medications. When compared to sertraline, initiation and adherence to bupropion resulted in a lower mean BMI-z of -0.15 (95% CI = -0.32, 0.02). No other medications were associated with statistically significantly different BMI-z changes compared to sertraline. The results were similar for 6-month outcomes. Results of initiation-only analyses were consistent with these results, although the effect estimates were attenuated.

Among youth, initiation and adherence to bupropion was not associated with 12-month BMI-z change, although 4 other most common antidepressants were associated with small increases in BMI-z over this time. Clinicians should consider these differences when prescribing antidepressants to youth, alongside US Food and Drug Administration approvals, clinical guidelines, and evidence of safety and efficacy.