Exploring Outcomes of Antidepressant Treatment and Polypharmacy in People with Comorbid Depression and Type 2 Diabetes

AIM: In adults with comorbid depression and type 2 diabetes (T2DM), to determine: Objective 1: The association between polypharmacy and antidepressant treatment trajectories; Objective 2: The association between antidepressants and long-term physical health outcomes. METHODS AND FINDINGS: In adults with comorbid depression and T2DM: I conducted two systematic reviews examining: i) Prevalence of antidepressant treatment and associated polypharmacy. The prevalence of antidepressant treatment varied from 18-87%. There was no evidence of an association between diabetes medication and antidepressant prescribing. I identified no studies investigating other polypharmacy. ii) Long-term outcomes of antidepressant treatment (no studies identified). I carried out four observational studies using electronic health record data from the UK Clinical Practice Research Datalink, to understand: Objective 1: i) Association between polypharmacy and stopping antidepressants before the recommended treatment duration: The median number of 7 concurrent medications was associated with a 65% decrease in the rate of stopping antidepressants (HR 0.45, 95% CI 0.37-0.55) compared to no concurrent medications. ii) Association between polypharmacy and restarting antidepressants: The median number of 9 concurrent medications was associated with a 64% increase in the rate of restarting antidepressant treatment (HR 1.64, 95% CI 1.44-1.86) compared to no concurrent medications. Objective 2: iii) The association between antidepressant prescribing and starting insulin: Antidepressants were associated with a 278% increase in the rate of starting insulin (IRR 3.78, 95% CIs 3.53-4.04). iv) The association between antidepressant prescribing and mortality: Antidepressants were associated with a 176% increase in the rate of all-cause mortality (RR 2.76, 95% CIs 2.53-3.01). CONCLUSIONS: Polypharmacy is associated with continuing and restarting antidepressants. Antidepressant prescribing is associated with worse long-term physical health outcomes. However, rather than a causal relationship, these are likely to be markers of worse depression severity which is in turn associated with worse long-term physical health outcomes