Does antidepressant use increase the risk of incident type 2 diabetes among youths?
In a cohort study of youths insured by Medicaid that included 119 608 youths who initiated antidepressant treatment, the current use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors—the most commonly used antidepressant subclass—was associated with an increased risk of incident type 2 diabetes that intensified with increasing duration of use, cumulative dose, and average daily dose.
The study findings provide an impetus to improve monitoring for benefits vs risks of antidepressant use in pediatric care models and to shed light on the underlying biological mechanism of antidepressant treatment–emergent type 2 diabetes.
Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment–emergent risk of type 2 diabetes among youths.
To assess the association between antidepressant use and the risk of incident type 2 diabetes in youths by antidepressant subclass and according to duration of use, cumulative dose, and average daily dose.
Design, Setting, and Participants
A retrospective cohort study was conducted using Medicaid claims data from 4 geographically diverse, large states of youths 5 to 20 years of age who initiated antidepressant treatment from January 1, 2005, to December 31, 2009.
Antidepressant use (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic or other cyclic antidepressants, and other antidepressants) was assessed using the following 4 time-varying measures: current or former use, duration of use, cumulative dose, and average daily dose.
Main Outcomes and Measures
Incident type 2 diabetes was assessed using discrete-time failure models, adjusting for disease risk score estimated using more than 125 baseline and time-dependent covariates.
In this cohort of 119 608 youths aged 5 to 20 years who initiated antidepressant treatment (59 087 female youths and 60 521 male youths; 54.7% between 5 and 14 years of age) with a mean follow-up of 22.8 months, 79 285 [66.3%] had SSRI or SNRI exposure. The risk of type 2 diabetes was significantly greater during current use than former use of SSRIs or SNRIs (absolute risk, 1.29 per 10 000 person-months vs 0.64 per 10 000 person-months; adjusted relative risk [RR], 1.88; 95% CI, 1.34-2.64) and tricyclic or other cyclic antidepressants (absolute risk, 0.89 per 10 000 person-months vs 0.48 per 10 000 person-months; RR, 2.15; 95% CI, 1.06-4.36), but not of other antidepressants (absolute risk, 1.15 per 10 000 person-months vs 1.12 per 10 000 person-months; RR, 0.99; 95% CI, 0.66-1.50). Furthermore, for youths currently using SSRIs or SNRIs, the risk of type 2 diabetes increased with the duration of use (RR, 2.66; 95% CI, 1.45-4.88 for >210 days and RR, 2.56; 95% CI, 1.29-5.08 for 151-210 days compared with 1-90 days) and with the cumulative dose (RR, 2.44; 95% CI, 1.35-4.43 for >4500 mg and RR, 2.17; 95% CI, 1.07-4.40 for 3001-4500 mg compared with 1-1500 mg in fluoxetine hydrochloride dose equivalents). By contrast, neither the duration nor the cumulative dose of other antidepressants was associated with an increased risk of type 2 diabetes. The risk of type 2 diabetes increased significantly with the average daily dose among youths with more than 150 days of SSRI or SNRI use (RR, 2.39; 95% CI, 1.04-5.52 for >15.0 vs ≤15.0 mg/d) but not among youths with 1 to 150 days of SSRI or SNRI use.
Conclusions and Relevance
In a large cohort of youths insured by Medicaid, the use of SSRIs or SNRIs—the most commonly used antidepressant subclass—was associated with an increased risk of type 2 diabetes that intensified with increasing duration of use, cumulative dose, and average daily dose.
Mehmet Burcu, Julie M. Zito, Daniel J. Safer, Laurence S. Magder, Susan dosReis, Fadia T. Shaya, Geoffrey L. Rosenthal. Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths. JAMA Pediatr. Published online October 16, 2017. doi:10.1001/jamapediatrics.2017.2896