New Research on Predicting Medication Nonadherence in Older Adults with Difficult-to-Treat Depression in the Incomplete Response in Late-Life Depression Getting to Remission Randomized Controlled Trial

Over 50% of depressed older adults do not achieve remission with first-line antidepressant treatment, and only half of older adults improve with augmentation or switch to another medication. Multiple factors contribute to poor treatment response including incorrect diagnosis, comorbid physical or psychiatric conditions, and somatic symptoms that overlap with other illnesses. Older adults also experience psychosocial challenges such as isolation and limited social support, which may interfere with treatment. Inadequately treated late-life major depression can have substantial negative health consequences.

A modifiable risk factor for poor treatment response is medication nonadherence. Failure to take medicine as prescribed increases with age, and nonadherence specifically to antidepressant medications in older adults is common.

A group of investigators, including Pitt Psychiatry scientists Helene Altmann, MD (PGY1 resident), Joseph Kazan, MD (postdoctoral scholar), Marie Anne Gebara, MD (Assistant Professor of Psychiatry), and Sarah Stahl, PhD (Assistant Professor of Psychiatry and Clinical and Translational Science), examined clinical and treatment factors predicting medication nonadherence in treatment-resistant late-life depression. They published the results in The American Journal of Geriatric Psychiatry

The investigators completed secondary analysis of data from a clinical trial of antidepressant pharmacotherapy for major depressive disorder in 468 adults over 60 years of age. In the trial, participants received venlafaxine XR for 12 weeks. Nonremitters were randomized to augmentation with either aripiprazole or placebo for 12 additional weeks. Medication adherence was self-reported by participants 14 times over 24 weeks. The analyses examined sociodemographic, clinical, and treatment factors that could predict antidepressant nonadherence during early, late, and augmentation treatment. “Numerous factors contribute to nonadherence, which makes it challenging to study. For example, an older adult who lacks transportation, has difficulty ambulating, and has mild cognitive decline may not be physically able to pick up their medications or may struggle to reach out to others for assistance. They may also have difficulty understanding and remembering why the medication is prescribed and how to correctly take medication. Thus, we looked at multiple possible factors which may contribute to nonadherence across the course of treatment,” said Dr. Altmann, the study’s first author.

Findings from the study showed that poor cognitive function and early response could predict early failure to take medication as prescribed. Poor cognitive function and prior nonadherence were predictive of late nonadherence. Living alone was associated with nonadherence both late and during augmentation treatment.

“These findings highlight the importance of patient education and the need for clinicians to explain to older adults that depression is like other chronic medical conditions that requires long-term symptom monitoring. Medication adherence was especially difficult for patients who live alone. Given the increased attention to the health effects of social isolation on health and wellbeing, our findings underscore the importance of including family members in treatment plans because they may be able to exert a positive influence on older adults’ health behaviors and promote adherence,” said Dr. Stahl, the study’s senior author.

Predicting medication nonadherence in older adults with difficult-to-treat depression in the IRL-GRey randomized controlled trial
Altmann HM, Kazan J, Gebara MA, Blumberger DM, Karp JF, Lenze EJ, Mulsant BH, Reynolds CF, Stahl ST

American Journal of Geriatric Psychiatry, March 2022,