The Overlooked Burden of Treatment-Resistant Depression

Guest authored by Kiranpreet Gill (University of Birmingham, UK)

Treatment-resistant depression (TRD) is a major public health concern that affects a substantial number of people, yet remains under-recognised in clinical care, policy, and research. It is associated with significant personal, social, and economic costs, as people with TRD often experience more severe symptoms, longer illness duration, and greater functional impairment compared to those with treatment-responsive depression. It also places considerable strain on healthcare systems due to frequent service use, hospital admissions, and complex care needs. Despite its prevalence and profound impact, TRD has not received the same level of attention as other mental health conditions. To help address this gap and further advance understanding in this area, we recently published a study examining the experiences, needs, and current treatment pathways of individuals with TRD.

Our study drew on data from 2,461 people diagnosed with major depressive disorder (MDD) in secondary care in the UK, combining both quantitative analysis and qualitative interviews with patients and clinicians. The quantitative data provided insights into patterns of diagnosis, treatment use, and comorbidities. The interviews offered a more personal and grounded account of how TRD is experienced in real life.

Characteristics of TRD

TRD is typically defined as depression that has not responded to at least two different antidepressant treatments. In our sample, nearly half (47 percent) of individuals with MDD met this criterion. In addition to experiencing persistent symptoms of depression, many people with TRD were also managing other difficulties, such as comorbid anxiety, personality disorders, physical health problems like diabetes and cardiovascular diseases, and socioeconomic disadvantage. Approximately 37 percent of people with TRD had also tried four or more different antidepressants within their current depressive episode. This pattern suggests that repeated pharmacological interventions, in the absence of broader therapeutic changes, may be insufficient in addressing the complexity of TRD.

Challenges Faced by Patients and Clinicians

Hearing directly from people living with TRD helped deepen our understanding of these numbers. Many described the emotional toll of moving from one treatment to another without noticeable benefit. Over time, this repeated disappointment led some to disengage from care altogether. For one individual, their experience was summed up as “years lost to inactivity,” a reflection of how long-term depression can limit daily activity and connection.

Clinicians voiced their own frustrations. Several described feeling that they had exhausted the available treatment options and lacked the resources or structured pathways to offer something different. Clinicians also noted that, compared to conditions like psychosis, services for TRD felt much less structured or supported. This left both clinicians and patients feeling unsupported and, at times, directionless. These observations point to broader systemic gaps in service planning and delivery, suggesting that current models may not be adequately equipped to respond to the complexity or persistence of TRD.

These accounts speak to a wider problem. People with TRD were often less likely to be referred to community mental health teams and more likely to receive care in specialist or inpatient settings, typically at a point of crisis. This suggests a pattern of reactive care, where people receive more intensive support only after their condition has worsened, rather than earlier in the course of illness. Several people living with TRD described their care as a process of “trial and error” that lacked coordination and clarity. For some, this unpredictability made it harder to continue seeking help.

Improving TRD Treatment Approaches

These experiences suggest that we need to change how we approach and manage TRD in services. Both patients and clinicians identified key areas for improvement. Treatment plans need to be more tailored and holistic, combining medication with psychological therapies such as cognitive behavioural therapy and compassion-focused therapy, depending on individual needs. TRD should be identified earlier so that people are not left cycling through medications without other forms of support. Care pathways also need to be clearer and more consistent, offering step-by-step guidance and continuity across time and services. Perhaps most importantly, people with TRD need to be supported in ways that go beyond symptom reduction, e.g., by focusing on improving everyday functioning, relationships, and overall well-being.

If adopted, these changes have the potential to reshape care for a group that has too often been overlooked. Improving care for people with TRD calls for a more coordinated and considered approach.

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