Depression and antecedent medication adherence in a cohort of new metformin users

The association between depression and poor medication adherence is based on cross-sectional studies and cohort studies that measure adherence rates after depression status is determined. However, depressive symptoms occur well before diagnosis. This study examined adherence patterns in the year before a depressive episode.

This retrospective cohort study followed new metformin users identified in Alberta Health's administrative data between 2008 and 2018. Depressive episodes starting ≥1 year after metformin initiation were identified using a validated case definition. Controls were randomly assigned a pseudo depression date. Adherence to oral antihyperglycemic medications was estimated using proportion of days covered (PDC) and group-based trajectory models to explore the association between depression and poor adherence (PDC<0.8).

A depressive episode occurred in 17,418 (10.6%) of 165,056 new metformin users. Individuals with depression were more likely to have poor adherence compared to controls (adjusted odds ratio 1.21; 95% CI 1.17, 1.26). Five trajectories were identified: nearly perfect adherence (PDC >0.95 [34.8% of cohort]), discontinued (PDC=0 [18.3% of cohort], poor initial adherence (PDC 0.75) that declined either rapidly (9.2% of cohort) or gradually (30.1% of cohort), and poor initial adherence (PDC 0.26) that increased gradually (7.6% of cohort). Individuals with depression were more likely to be in one of the four trajectories of poor adherence compared to controls (adjusted odds ratio 1.24; 95% CI 1.19-1.29).

Poor medication adherence occurs in the year before a depressive episode; therefore, poor medication use patterns could be used as an early warning sign for depression.