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

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with type 2 diabetes mellitus (T2DM) in youths, possibly via 5-HT2C, H1 receptors and serotonin transporter (SERT). SSRIs have similar affinity for SERT but variable affinity for 5-HT2C and H1. This study assessed whether SSRIs with strong affinity for 5-HT2C 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.

Prescribing Trends of Antidepressants and Psychotropic Coprescription for Youths in UK Primary Care, 2000-2018.

BACKGROUND: There is lack of recent information on the prescribing trends of antidepressants and coprescription with other psychotropic medications in the United Kingdom (UK) pediatric population. METHODS: Using the Clinical Practice Research Datalink, we estimated the annual rates of patients newly prescribed an antidepressant (selective serotonin reuptake inhibitors (SSRIs), other newer generation antidepressants, and tricyclic antidepressants (TCAs)) and the percentage of new users of antidepressants with a same-day coprescription for other psychotropic medications. We also estimated the prevalence of patients with antidepressant prescriptions and percentage of coprescription for other psychotropic medications. RESULTS: After a 42% decline from 2000 to 2005, the rate of patients newly prescribed an antidepressant increased from 2006 onwards. From 2008 to 2018, the rate increased from 254.3 to 471.2 per 100,000 person-years (rate ratio 1.97, 95% confidence interval 1.96-1.99). The rate was higher in females and adolescents aged 15 to 17. SSRIs were most commonly prescribed (70% of all antidepressant prescriptions). Overall, 4.7% of patients newly prescribed an antidepressant had at least one same-day coprescription for another psychotropic medication. During the study period, coprescription rose from 2.6% to 6.4% and was more frequent in males. In 2018, most coprescriptions were anxiolytics and hypnotics (63%) and antipsychotics (26%). Trends in prevalent prescriptions corresponded to trends in new prescriptions. LIMITATIONS: By using a primary care database, we did not have information on prescriptions from specialists or during hospitalizations. CONCLUSIONS: During the last decade, antidepressant prescriptions and psychotropic coprescription in primary care increased in UK children and adolescents.