Comparative BMI-z Changes With Initiation and Adherence to Antidepressant Medications Among Youth - 20/12/25

Doi : 10.1016/j.jaac.2025.11.008

Sheryl L. Rifas-Shiman, MPH ^a,^⁎ , Jessica G. Young, PhD ^a,^b, Han Yu, PhD ^a, Matthew F. Daley, MD ^c, William J. Heerman, MD, MPH ^d, David M. Janicke, PhD ^e, W. Schuyler Jones, MD ^f, Kristina H. Lewis, MD, MPH ^g, Pi-I.D. Lin, ScD ^a, Carly Prentice, MSN, APRN, FNP-C ^h, L. Charles Bailey, MD, PhD ⁱ, Sengwee Toh, ScD ^a, Joshua Petimar, ScD ^a,^b,^{^{#
Joshua Petimar and Jason P. Block are co–senior authors of this work.}}, Jason P. Block, MD, MPH ^a,^{^{#
Joshua Petimar and Jason P. Block are co–senior authors of this work.}}

^a Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts

^b Harvard T.H. Chan School of Public Health, Boston, Massachusetts

^c Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado

^d Vanderbilt University Medical Center, Nashville, Tennessee

^e College of Public Health and Health Professions, University of Florida, Gainesville, Florida

^f Duke University Health System, Durham, North Carolina

^g Wake Forest University School of Medicine, Winston-Salem, North Carolina

^h Faith Family Medical Center, Nashville, Tennessee

ⁱ Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

^∗ Correspondence to Sheryl L. Rifas-Shiman, MPH, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Drive, Suite 401E, Boston, MA 02215 Department of Population Medicine Harvard Medical School and Harvard Pilgrim Health Care Institute 401 Park Drive Suite 401E Boston MA 02215

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 20 December 2025

Abstract

Objective

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.

Method

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.

Results

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.

Conclusion

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.

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Key words : body mass index, weight gain, antidepressant medications, pediatrics

Plan

Method

Measures of Initiation and Adherence

CRediT authorship contribution statement

	This work was supported by the National Institutes of Health (5R01DK120598 from NIDDK). The funders had no role in the design and conduct of the study.
	The data used in this article cannot be made public due to PCORnet regulations aimed at safeguarding the privacy of study participants. However, researchers can access PCORnet data for research purposes by following the formal policies and procedures set by PCORnet.
	Jessica Young and Joshua Petimar served as the statistical experts for this research.
	Sheryl L. Rifas-Shiman, Jessica Young, Han Yu, Matthew F. Daley, William J. Heerman, David M. Janicke, W. Schuyler Jones, Kristina H. Lewis, Pi-I D. Lin, Carly Prentice, L. Charles Bailey, Sengwee Toh, Joshua Petimar, and Jason P. Block have reported no biomedical financial interests or potential conflicts of interest.