(Y) The Impact of Polypharmacy on Antidepressant Discontinuation in Comorbid Depression and Type 2 Diabetes: A UK Primary Care Record Cohort Study

Publication Number: 648

Background: Polypharmacy may increase the risk of drug interactions, side-effects and poor adherence. There is a bidirectional association between depression and T2DM, with polypharmacy common in comorbid individuals; however, the impact of polypharmacy on antidepressant use in individuals with T2DM is unknown.

Objectives: In adults with T2DM, we aimed to investigate the association between the number of prescribed medications and early antidepressant discontinuation (duration < 32 weeks), specifically: (i) discontinuation of antidepressants altogether; and (ii) switching antidepressant agents. We hypothesised that polypharmacy would be associated with higher risk of antidepressant discontinuation.

Methods: We performed a cohort study using UK primary care data from the Clinical Practice Research Datalink (CPRD) in the years 2000-2018. Our cohort included participants with comorbid depression and T2DM, who started antidepressant treatment during their electronic health record (EHR) follow-up. Our outcome was early (duration < 32 weeks) antidepressant discontinuation, defined by at least 60 days without any antidepressant prescription. We used cox regression models with penalised B-splines to describe the association between the number of concurrent medications prescribed at the time starting antidepressant treatment, and early antidepressant discontinuation.

Results: We identified 73,808 individuals with comorbid depression and T2DM starting antidepressant treatment. The median number of concurrent medications prescribed at start of antidepressant treatment was 7. Within 32 weeks, 44.26% of participants discontinued antidepressant treatment altogether, and 11.75% of participants switched antidepressant agents. For each additional concurrent medication, the rate of discontinuing antidepressant treatment altogether decreased, until a maximum association was reached at 18 concurrent medications. The median number of 7 concurrent medications was associated with a 65.06% decrease in the rate of a discontinuing antidepressant treatment altogether (HR 0.45, 95% CIs 0.37-0.55). We found no evidence of an association between the number of concurrent medications and switching antidepressant agents.

Conclusions: Early discontinuation of antidepressants is common in adults with T2DM. However, individuals who received more concurrent prescriptions at the start of antidepressant treatment may be more adherent to antidepressant treatment. Individuals with fewer concurrent medications may represent individuals with less complex T2DM, who have less contact with services, or who are less compliant to treatment – these individuals are potentially at risk for early antidepressant discontinuation, and may benefit from adherence support.