Is the risk of T2D with SSRIs as substantial as was initially reported?
Selective Serotonin Reuptake Inhibitors (SSRIs) are common antidepressants used to treat children and adolescents. A previous study found a substantially increased risk of type 2 diabetes in Medicaid-insured children prescribed SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs). An association between SSRIs and T2D has also been reported in adult studies, with the potential mechanism being attributed to weight gain while using SSRIs. A new study found the magnitude and risk of this association in children to be much smaller than other known risk factors for T2D. Sun et al. reported the risk of T2D in publicly insured youths ages 10-19 to be much lower than initially reported, and concluded that it is less of a concern when it comes to safety in this patient population.
This cohort study aimed to assess the association between SSRIs and T2D risk and evaluate SSRIs’ safety in children and adolescents. Two US databases, IBM Marketscan (privately insured) and the Medicaid Analytic eXtract (publicly insured) were used to identify the target population of patients ages 10-19 years old with a diagnosed indication for SSRI use. The exposed group consisted of new users of SSRIs. In contrast, the untreated group consisted of patients with a diagnosed indication for SSRI therapy but no current antidepressant use or history of antidepressant use. Each SSRI user was matched with two age-matched untreated patients with a medical encounter within 14 days (before or after) of the SSRI users index date or the first observed SSRI dispensing date. The baseline characteristics were measured within the 365 days before the patient index date, and included demographics, use of health care, medical diagnosis (mainly psychiatric), and concomitant medications. The baseline characteristics were consistent across all treatment groups.
This study intended to treat analysis restricted to patients with ≥1 additional prescription within six months of the index date and as–treated research to assess the association of continuous SSRI use against untreated patients, bupropion treatment, and psychotherapy. (Sun et al.) The designated follow-up period began 180 days after the index date with the mean follow-up times in the ITT cohort being 2.3 and 2.2 years in the publicly and privately insured groups. This study’s primary outcome was the first diagnosis of T2D, based on inpatient/outpatient diagnosis of T2D and the use of anti–diabetic medication. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals. (Sun et al.)
The primary ITT analysis included 1,582,914 patients, 316,178 publicly insured patients, and 211,460 privately insured patients in the exposed group, and 632,356 and 422,920 age-matched patients in public and private insured untreated groups, respectively. Unadjusted incidence rates of T2DM were 2.32 cases per 1000 person-years in the exposed group vs. 1.65 cases per 1000 person-years in the untreated group in the publicly insured patient population. Once adjusted, an association was seen between SSRI use and risk of T2D (aHR, 1.13; 95% CI, 1.04-1.22). In the privately insured patients, no increased risk was seen in the exposed group (aHR, 1.10; 95% CI, 0.88-1.36).
The as-treated analysis also showed an increased risk of T2D in the exposed population with an additional 6.6 (95% CI, 4.2-10.4) T2DM cases per 10,000 continuously treated patients for ≥ 2 years and 28.4 (95%, 16- 46.3) T2DM cases per 10,000 continuously treated patients for ≥ 5 years. The number needed to harm the exposed population was 1515, and 352 patients were treated for ≥ 2 and ≥ 5 years, respectively. The association between SSRIs and T2D risk did not manifest until > 1 year of therapy with SSRIs in both the ITT and as-treated analysis. Within the SSRI class, HR did not vary between agents when compared to fluoxetine.
As the incidence of type 2 diabetes in children continues to rise, proper management of risk factors associated with T2D can prevent or delay this condition’s onset. Sun et al. found that this risk was lower, posing less of a concern for youth safety than other established risks for type 2 diabetes, although a previous study found a substantially greater risk (RR, 1.88; 95% CI, 1.34-2.64). The risk of T2D should be weighed against other associated risks with SSRI use when managing use in children and adolescents.
- The association between SSRIs and risk for T2DM did not manifest until > 1 year of therapy with SSRIs.
- The risk for T2DM did not vary between SSRIs.
- Although significantly smaller than initially reported, the risk of T2DM should be weighed against other known risks for SSRI use when making therapeutic decisions for children and adolescents.
Sun, Jenny W. et al. “Association Of Selective Serotonin Reuptake Inhibitors With The Risk Of Type 2 Diabetes In Children And Adolescents”. JAMA Psychiatry, 2020. https://doi.org/10.1001/jamapsychiatry.2020.2762. Accessed 15 Sept 2020.
Burcu, Mehmet et al. “Association Of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths”. JAMA Pediatrics, vol 171, no. 12, 2017, p.1200. https://doi.org/10.1001/jamapediatrics.2017.2896. Accessed 17 Sept 2020.
Destiny Reed, PharmD. Candidate, Florida A&M College of Pharmacy and Pharmaceutical Sciences