Disclosures: Sun reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
September 14, 2020
2 min read

SSRI use linked to small increased risk for type 2 diabetes among youth

Disclosures: Sun reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Children and adolescents who initiate selective serotonin reuptake inhibitors appeared at a small increased risk for type 2 diabetes, according to results of a cohort study published in JAMA Psychiatry.

However, the magnitude of the association was smaller than previously reported.

“Children and adolescents are often excluded from randomized clinical trials, resulting in a lack of evidence on medication safety and widespread off-label prescribing,” Jenny W. Sun, PhD, of the department of epidemiology at Harvard T.H. Chan School of Public Health, and colleagues wrote. “Rapid changes in growth during childhood and adolescence can alter drugs’ pharmacokinetics and pharmacodynamics, so high-quality age-specific drug safety data are needed to inform prescribing decisions. Because it is unlikely that a sufficiently large [randomized clinical trial] will be conducted to study SSRIs and [type 2 diabetes] in young patients, evidence must be generated using real-world data.”

Several studies found evidence of an association between SSRIs and type 2 diabetes among adults; however, overall data are scarce but needed, given the widespread prescription of SSRIs and potential health threats related to type 2 diabetes during youth, according to the researchers.

In the current study, Sun and colleagues this potential association among children aged 10 to 19 years who had a diagnosis for an SSRI treatment indication according to the nationwide Medicaid Analytic eXtract (MAX) and the IBM MarketScan databases. The analysis included 1,582,914 patients, of whom 316,178 in the MAX database and 211,460 in the MarketScan database were SSRI-treated. Exposures included new SRRI medication users and comparator groups with no known metabolic adverse effects. The researchers compared within-class individual SSRI medications with fluoxetine hydrochloride. Incident type 2 diabetes during follow-up served as the main outcome.

Results showed SSRI treatment initiation was linked to a 13% increased risk for type 2 diabetes (intention-to-treat adjusted hazard ratio [aHR] = 1.13; 95% CI, 1.04-1.22) vs. untreated patients. Sun and colleagues observed a strengthened association for continuous SSRI treatment (as-treated aHR = 1.33; 95% CI, 1.21-1.47), which corresponded to 6.6 additional cases of type 2 diabetes per 10,000 patients treated for 2 or more years. Among privately insured patients, adjusted hazard ratios appeared lower, with an intention-to-treat adjusted hazard ratio of 1.01 (95% CI, 0.84-1.23) and an as-treated adjusted hazard ratio of 1.1 (95% CI, 0.88-1.36). The researchers reported similar findings when comparing SSRI treatment with psychotherapy; however, they observed no increased risk compared with bupropion treatment.

No medication was associated with an increased risk for type 2 diabetes compared with fluoxetine for the within-class analysis.

“The magnitude of association was more modest than previously reported, and the absolute risk was small, providing evidence that this safety concern is not as substantial as initially reported,” Sun and colleagues wrote. “This potential risk, which is much lower in magnitude than the other known risk factors for [type 2 diabetes], should be weighed against the known benefits and risks of SSRI treatment to help inform treatment decision making in the pediatric population.”