Selective serotonin reuptake inhibitors and the risk of type 2 diabetes mellitus in youths

Abstract

Background: Selective serotonin reuptake inhibitors (SSRIs) have been associated with type 2 diabetes mellitus (T2DM) in youths, possibly via 5-HT_2C, H₁ receptors and serotonin transporter (SERT). SSRIs have similar affinity for SERT but variable affinity for 5-HT_2C and H₁. This study assessed whether SSRIs with strong affinity for 5-HT_2C and H₁ (relative to SERT) were associated with T2DM risk compared with weak-affinity SSRIs.

Methods: Using the UK Clinical Practice Research Datalink, we assembled a cohort of patients aged 5-24, newly prescribed a strong-affinity SSRI (citalopram, escitalopram, fluoxetine) or weak affinity (paroxetine, sertraline, fluvoxamine) between 1990 and 2019. We controlled for confounding using standardized mortality ratio weighting, estimated from calendar time-specific propensity scores. We used weighted Cox proportional hazards models to estimate hazard ratios (HRs) of incident T2DM with 95 % confidence intervals (CIs).

Results: The cohort included 347,368 new users of strong-affinity SSRIs and 131,359 of weak-affinity SSRIs. Strong-affinity SSRIs were not associated with an increased T2DM risk compared with weak-affinity SSRIs (incidence rate 2.8 vs 2.7 per 1000 person-years; HR 1.03, 95 % CI 0.85-1.25). T2DM risk did not vary with duration of use, age or sex. However, the HR was numerically higher in youths with normal or low weight (HR 1.30, 95 % CI 0.85-1.98) and with prior antipsychotic use (HR 1.62, 95 % CI 0.83-3.18).

Limitations: Median duration of SSRI use, in line with real-world SSRI prescribing, was relatively short.

Conclusion: T2DM risk did not differ between strong- and weak-affinity SSRIs, providing reassurance for clinicians when choosing between SSRIs in youths.

Keywords: Antidepressants; Children; Diabetes; SSRIs; UK.