Risks of antidepressants on cardiovascular mortality and morbidity, suicidality, falls and fractures in people with obesity and depression in primary care

Date of ISAC Approval: 
08/02/2019
Lay Summary: 
In large studies of patients from primary care records, selective serotonin reuptake inhibitor (SSRI), tricyclic and other antidepressant drugs show differences in serious outcomes. People with obesity are more likely to have depression and to be prescribed antidepressants than other people. Antidepressants lead to weight gain to a variable degree. In people with obesity, antidepressants might have different risks for serious outcomes such as death due to heart disease and stroke, other non-fatal diabetes and cardiovascular events, suicide and self-harm, fractures and falls. We will find out if different classes of antidepressant drugs and commonly prescribed antidepressant drugs are linked with serious outcomes in people who are overweight or obese. We will do this in people with a first episode of depression that is treated with no antidepressant, a selective serotonin reuptake inhibitor, tricyclic or other antidepressant. We will also look at different types of antidepressants. We will compare each serious outcome in each class of antidepressant or no antidepressant. We will do this by looking at anonymised patient records from the Clinical Practice Research Datalink (CPRD) linked to hospital records and deaths. We will consider in our analysis other risks for these outcomes such as smoking, other prescribed drugs and other physical and mental health conditions. We will work with our patient and public representatives on how best to present this information to help patients and prescribers make the best decisions when considering the use of antidepressant drugs for depression in people who are overweight or obese.
Technical Summary: 
In population cohort studies using primary care records linked to hospital episode statistics and records of deaths, selective serotonin reuptake inhibitor, tricyclic and other antidepressants show differences in serious outcomes such as suicide, fractures and mortality. People with obesity are more likely to have depression and to be prescribed antidepressants than other people. Cohort studies show that antidepressants vary in relation to weight gain so it is possible that they might have different risks for cardiovascular mortality and diabetes outcomes as well. Using CPRD linked to hospital episode statistics and mortality records, we will determine the relative risk of the most commonly prescribed antidepressants and antidepressant classes on serious outcomes related to cardiovascular health, mortality, diabetes and suicidality in people with first episode depression who were previously found to be overweight or obese. We will use Cox proportional hazards modelling to assess the effect of individual antidepressants and classes of antidepressants on the serious outcomes. We will control for confounding variables such as smoking, alcohol intake, other prescribed medication, other physical and mental health diagnostic comorbidities known to be associated with cardiovascular outcomes, mortality and depression outcomes. We will co-produce the presentation of our results with patients and public representatives to be informative to patients and prescribers alike.
Health Outcomes to be Measured: 
- cardiovascular disease and mortality - all-cause mortality - Suicidality/Self-harm - diabetes mellitus - Fractures/Falls
Collaborators: 

Professor Richard Morriss - Chief Investigator - University Of Nottingham
Dr Francesco Zaccardi - Collaborator - University Of Leicester
Ms Freya Tyrer - Collaborator - University Of Leicester
Professor Kamlesh Khunti - Collaborator - University Of Leicester
Professor Richard Morriss - Corresponding Applicant - University Of Nottingham

Linkages: 
HES Admitted;ONS;Patient IMD