Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths

Abstract

Importance: 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.

Objective: 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.

Exposures: 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.

Results: 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.

Figure 1.. Flowchart for the Study Cohort of Youths Insured by Medicaid (5-20 Years of Age) Who Were New Users of Antidepressant Medications, 2005-2009

^aLife-threatening or serious somatic conditions included sickle cell disease, cystic fibrosis, cerebral palsy, cancer, HIV infection, organ transplant, dialysis or end-stage renal disease, respiratory failure, aplastic anemia, congenital immune deficiencies, Down syndrome, other lethal chromosomal anomalies, fatal metabolic diseases, and serious neuromuscular disease.

Figure 2.. Risk of Incident Type 2 Diabetes By Average Daily Dose According to Duration of Use Among Youths Insured by Medicaid (5-20 Years of Age) Who Were Current Users of SSRIs or SNRIs, 2005-2009

The risk of type 2 diabetes increased significantly with the average daily dose (in fluoxetine hydrochloride dose equivalents), with a relative risk [RR] of 1.96 (95% CI, 1.05-3.64) for more than 30.0 mg/d and an RR of 1.83 (95% CI, 1.04-3.24) for 15.1 to 30.0 mg/d compared with 15.0 mg/d or less. For youths with 1 to 150 days of selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) use, the average daily dose was not significantly associated with an increased risk of type 2 diabetes (RR, 1.22; 95% CI, 0.57-2.63). For youths with more than 150 days of SSRI or SNRI use, more than 15.0 mg/d was associated with a 2.39-fold (95% CI, 1.04- to 5.52-fold) increased risk of type 2 diabetes compared with 15.0 mg/d or less. Relative risk is adjusted for disease risk score (expressed as percentile ranks), time from cohort entry (ie, follow-up month), and exposures to tricyclic and other related cyclic antidepressants and other antidepressants. Error bars indicate 95% CIs.