Dissertation
Clinical effects of compliance with antidepressants on glycemic control in adults treated for comorbid type 2 diabetes mellitus and major depressive disorder
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2026
DOI:
https://doi.org/10.17918/00011413
Abstract
Background: Adults with type 2 diabetes mellitus (T2DM) experience disproportionately high rates of comorbid major depressive disorder (MDD), a combination associated with poorer self-management, reduced medication adherence and worse clinical outcomes. Despite the clinical importance of treating both conditions, evidence regarding how antidepressant use and adherence behaviors influence glycemic control remains limited and methodologically inconsistent. Objectives: This dissertation examined the real-world relationship between antidepressant use and glycemic control among adults with treated T2DM and comorbid MDD across three aims: (1) characterizing baseline differences between antidepressant initiators and non-initiators, (2) estimating the association between antidepressant initiation and glycemic control with explicit attention to compliance and persistence, and (3) formally evaluating whether compliance and persistence mediate the antidepressant-glycemic control relationship. Methods: A retrospective cohort study was conducted using the Optum® Clinformatics® Data Mart (2007-2025), a longitudinal administrative claims database linked with laboratory data. Adults with treated T2DM, a diagnosis of MDD and longitudinal HbA1c measurements were included. Propensity score inverse probability weighting targeting the average treatment effect on the treated (ATT) was applied to address confounding by indication. Population-averaged generalized estimating equation (GEE) logistic models estimated associations between antidepressant initiation and glycemic control (HbA1c <7%). Causal mediation analysis within a counterfactual framework decomposed total effects into direct and indirect components operating through compliance (MPR [greater than or equal to] 80%) and persistence (PDC [greater than or equal to] 80%). Results: The analytic cohort included 19,542 adults with treated T2DM and MDD. After ATT weighting, antidepressant initiation was associated with an 18% reduction in the odds of achieving glycemic control (OR = 0.82; 95% CI: 0.75, 0.90), corresponding to an absolute risk difference of 4.1 percentage points. Baseline diabetes severity --particularly insulin use and baseline HbA1c -- was the strongest predictor of glycemic outcomes. Neither antidepressant compliance nor persistence was independently associated with glycemic control among treated patients. Causal mediation analyses demonstrated that indirect effects operating through compliance and persistence were negligibly small and not statistically distinguishable from zero across all analytic specifications. Conclusions: In this real-world cohort, antidepressant initiation was associated with lower likelihood of glycemic control, and antidepressant medication-taking behaviors did not meaningfully mediate this relationship. These findings highlight the dominant influence of diabetes severity on glycemic outcomes, suggest that antidepressant initiation functions primarily as a marker of broader clinical complexity, and underscore the need for integrated, multifactorial care strategies for adults managing comorbid T2DM and MDD.
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Details
- Title
- Clinical effects of compliance with antidepressants on glycemic control in adults treated for comorbid type 2 diabetes mellitus and major depressive disorder
- Creators
- Chioma Ada Uzoigwe
- Contributors
- Longjian Liu (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University
- Number of pages
- ix, 116 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Dana and David Dornsife School of Public Health; Epidemiology and Biostatistics; Drexel University
- Other Identifier
- 991022189169504721