Selective Serotonin Reuptake Inhibitors and the Risk of Type 2 Diabetes Mellitus in Children and Youths

Date of ISAC Approval: 
29/06/2020
Lay Summary: 
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs called antidepressants, often prescribed in children and youths to treat depression. Concerns have emerged that SSRIs may increase the risk of high blood sugar levels and cause type 2 diabetes. However, whether the risk of diabetes varies between individual SSRIs is unclear. Indeed, individual SSRI drugs have different mechanisms of action that may affect weight gain and blood sugar levels. Thus, SSRIs with a stronger effect on weight and blood sugar levels may be associated with a higher risk of diabetes. This study will use the United Kingdom Clinical Practice Research Datalink to assess whether the use of SSRIs with stronger effects on weight gain and blood sugar levels increase the risk of diabetes compared with SSRIs with a weak effect. Given the serious, long-lasting consequences of diabetes in children and youths, this study will provide information on the differences between SSRIs to inform treatment choice when prescribing an SSRI.
Technical Summary: 
SSRIs are the most commonly prescribed antidepressants in children and youths in the United Kingdom. A steady increase in the rate of SSRIs prescriptions has been observed in the last two decades in this population. However, several studies in adults and one study in children and youths suggest that SSRIs may increase the risk of type 2 diabetes mellitus (T2DM). While these studies evaluated the risk of T2DM associated with SSRIs as a class, whether differences exist between individual SSRIs is unclear. Indeed, individual SSRIs have different pharmacodynamic mechanisms, which may in turn induce different glycaemic and metabolic effects. The main mechanism of action of SSRIs involves the serotonin transporter, but affinity to other receptors with metabolic effects varies amongst SSRIs. Thus, SSRIs with higher binding affinity to these receptors may be associated with a higher risk for T2DM. We will conduct a cohort study to assess whether the use of SSRIs with strong binding affinity is associated with an increased risk for T2DM compared with use of SSRIs with weak binding affinity. The cohort will comprise all patients aged 5 to 24 years with a first prescription for an SSRI between 1990 and 2019. We will use Cox proportional hazards models to estimate the hazard ratios of T2DM associated with the use of SSRIs with strong binding affinity compared with SSRIs with weak binding affinity. Secondary analysis will explore whether the risk varies with duration of use. We will also conduct sensitivity analyses to assess the robustness of our results.
Health Outcomes to be Measured: 
Type 2 diabetes mellitus (T2DM).
Collaborators: 

Dr Samy Suissa - Chief Investigator - McGill University
Christel Renoux - Corresponding Applicant - McGill University
Christopher Filliter - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Mrs Dai Cao - Collaborator - McGill University
Dr Emma Fergusson - Collaborator - Oxford University Hospitals
Dr Francois Montastruc - Collaborator - University Of Toulouse
Dr Laurent Azoulay - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Dr Soham Rej - Collaborator - McGill University