New Insights Into Treatment Resistant Depression Show Gaps in Care: Daily Dose

_{©New Africa/AdobeStock}

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On March 25, 2025, we reported on a study published in the British Journal of Psychiatry that examined clinical and service-level associations of treatment-resistant depression (TRD), and the experiences of individuals with TRD and clinicians involved in their care.

The study

Researchers conducted a mixed-methods study that integrated quantitative analysis of electronic health records with thematic analysis of semi-structured interviews. The quantitative component of the study analyzed electronic health records from 5136 adults (mean age 49 years) diagnosed with major depressive disorder (MDD). Of these, 2461 (47.92%) were identified as having TRD, defined as depression that has failed to respond to at least 2 sequential antidepressant trials at adequate doses. The remaining 52.8% were classified as having MDD.

The findings

Investigators reported significantly higher recurrence of depressive episodes among those with TRD compared to those without (31.76% vs 26.62%; P <.001) as well as significantly greater rates of mental health comorbidities including anxiety disorders (30.80% vs 18.17%; P =.015), personality disorders (16.54% vs 11.18%; P <.001), self-harm (2.70% vs 0.90%, P <.001) and psychotic illness (15.03% vs 8.30%; P <.001). Physical comorbidities were also significantly higher among adults with TRD, including cardiovascular, respiratory, and gastrointestinal diseases as well as rates of both type 1 and type 2 diabetes.

Qualitative interviews conducted with participants experiencing TRD and their clinicians provided deeper insights into challenges of effective treatment. Through thematic, researchers discovered frustration in both groups with existing treatment pathways. For patients, this was often linked to organizational challenges and a perceived lack of support from health care providers. For their part, clinicians voiced frustration with current treatment guidelines, noting they often did not address the complex needs of their patients, leaving them feeling ill equipped to make treatment decisions.

Participants linked severe emotional distress to ineffective treatments and many expressed feelings of hopelessness following repeated treatment failure. Clinicians acknowledged their own feelings of helplessness faced with sequential treatment failures in their patients with TRD.

Authors' comments

"This study is important as the data demonstrates people with TRD are at a higher risk of a range of poorer outcomes, and that we need better defined care pathways for helping this population, and are in urgent need of developing and testing new treatments for this group."

Click here for more details.