Background: Previous studies have reported that health literacy limitations are associated with poorer disease control for chronic conditions, but have not evaluated potential associations with medication adherence.

Objective: To determine whether health literacy limitations are associated with poorer antidepressant medication adherence.

Design: Observational new prescription cohort follow-up study.

Participants: Adults with type 2 diabetes who completed a survey in 2006 and received a new antidepressant prescription during 2006-2010 (N = 1,366) at Kaiser Permanente Northern California.

Main measures: Validated three-item self-report scale measured health literacy. Discrete indices of adherence based on pharmacy dispensing data according to validated methods: primary non-adherence (medication never dispensed); early non-persistence (dispensed once, never refilled); non-persistence at 180 and 365 days; and new prescription medication gap (NPMG; proportion of time that the person is without medication during 12 months after the prescription date).

Key results: Seventy-two percent of patients were classified as having health literacy limitations. After adjusting for sociodemographic and clinical covariates, patients with health literacy limitations had significantly poorer adherence compared to patients with no limitations, whether measured as early non-persistence (46 % versus 38 %, p < 0.05), non-persistence at 180 days (55 % versus 46 %, p < 0.05), or NPMG (41 % versus 36%, p < 0.01). There were no significant associations with primary adherence or non-persistence at 365 days.

Conclusions: Poorer antidepressant adherence among adults with diabetes and health literacy limitations may jeopardize the continuation and maintenance phases of depression pharmacotherapy. Findings underscore the importance of national efforts to address health literacy, simplify health communications regarding treatment options, improve public understanding of depression treatment, and monitor antidepressant adherence.