More than one-third of patients underwent four or more antidepressant trials during a single depressive episode, according to a recent study.
The study's researchers examined the clinical characteristics, service use, and lived experiences of patients with treatment-resistant depression (TRD) compared with those with major depressive disorder (MDD). Using data from a large U.K. secondary care population, the researchers, led by Kiranpreet Gill of the Institute for Mental Health, School of Psychology at the University of Birmingham in Birmingham, U.K., aimed to assess prevalence, treatment pathways, and the burden associated with TRD in both quantitative and qualitative analyses.
According to the study published in The British Journal of Psychiatry, the quantitative component involved a retrospective analysis of deidentified electronic health records from 5,136 adults diagnosed with MDD between 1996 and 2021. Patients with comorbid bipolar disorder, psychosis-related, dementia-related, or neurological conditions were excluded. TRD was defined according to the British Association for Psychopharmacology and Maudsley Prescribing Guidelines criteria as nonresponse to at least two adequate trials of antidepressants followed by a third pharmacologic strategy or augmentation. Among those who met eligibility criteria, 2,461 patients (47.9%) met TRD criteria. Notably, 36.9% of patients with TRD had trialed four or more antidepressants within a single episode.
Patients with TRD exhibited higher rates of recurrent depression (31.8% vs 26.6%; P < .001), comorbid anxiety disorders (30.8% vs 24.5%; P < .001), personality disorders (16.5% vs 11.2%; P < .001), psychotic illness (15% vs 8.3%; P < .001), and self-harm (2.7% vs 0.9%; P < .001) compared with those with nonresistant MDD. Cardiovascular comorbidities were more common in the TRD group (5.5% vs 3.3%; P < .001), as were smoking-related diagnoses (6.9% vs 4.6%; P < .001) and type 2 diabetes (5.9% vs 3.9%; P < .001). TRD patients also had significantly greater rates of economic inactivity (41.2% vs 32.6%; P < .001).
Binary logistic regression revealed that TRD status was independently associated with psychotic illness (odds ratio [OR] = 1.59; 95% confidence interval [CI] = 1.27–2), anxiety disorders (OR = 1.21; 95% CI = 1.03–1.41), personality disorders (OR = 1.35; 95% CI = 1.1–1.65), cardiovascular disease (OR = 1.46; 95% CI = 1.02–2.07), and self-harm (OR = 1.76; 95% CI = 1.06–2.93).
The qualitative component involved semistructured interviews with 15 patients (eight clinicians and seven patients with TRD who were 28 to 63 years old). Thematic analysis identified barriers to effective care, including inconsistent terminology, limited psychological service access, and perceived treatment failure. Patients expressed frustration with trial-and-error pharmacologic strategies and called for a more individualized, holistic approach.
These findings highlight the complexity and burden of TRD in secondary care. The researchers recommended clearer classification standards, early identification of treatment resistance, and improved access to tailored psychological and biological interventions.
No conflicts of interest were reported.
