Intervention key for major depressive disorder to prevent treatment-resistant depression

For those with major depressive disorder, early intervention is crucial to address treatment-resistant depression, which may lead to higher disease burden on the patient and health care system, per a study published in JAMA Psychiatry.

“Major depressive disorder [MDD] is the leading cause of disability worldwide,” Johan Lundberg, MD, PhD, of the Centre for Psychiatry Research at Karolinska Institute’s department of clinical neuroscience, and colleagues wrote. “Spontaneous remission of depressive episodes typically occurs within months or years, but a substantial number of patients do not experience a reduction in symptoms after several months and numerous treatment attempts.”

Researchers aimed to estimate the burden of treatment-resistant depression (TRD) in a large population-wide cohort in an area with universal health care by including data from both health care types (psychiatric and nonpsychiatric) and, further, to develop a prognostic model for clinical use.

Their population-based observational cohort study included information from the Stockholm MDD Cohort for MDD episodes between 2010 and 2017, that fulfilled predefined criteria for TRD (three or more consecutive antidepressant treatments).

Researchers identified a total of 158,169 unipolar MDD episodes among 145,577 individuals between January 2012 and December 2017 (64.7% women; median age, 42 years). From this initial cohort, 12,793 episodes (11%) qualified for consideration as TRD. Main outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality and intentional self-harm, and TRD in the prognostic model. Data analysis was performed from August 2020 to May 2022.

Results showed the median time from the start of an MDD episode to TRD was 552 days. Selective serotonin reuptake inhibitors served as the most common class of antidepressant treatment in all treatment steps, and 5,907 patients (46.2%) received psychotherapy at some point before the third antidepressant treatment. Data additionally revealed that, compared with matched non-TRD episodes, TRD episodes had more inpatient bed-days (mean, 3.9 days; 95% CI, 3.6-4.1 vs. 1.3 days; 95% CI, 1.2-1.4) and more lost workdays (mean, 132.3 days; 95% CI, 129.5-135.1 vs. 58.7 days; 95% CI, 56.8-60.6) 12 months after the index date.

Anxiety, stress, sleep disorder and substance use disorder all occurred more commonly in TRD episodes. Intentional self-harm was more than four times more common in TRD episodes.

The researchers found the severity of MDD, defined using the self-rating Montgomery-Åsberg Depression Rating Scale at time of MDD diagnosis, to be the most important prognostic factor for TRD (C index= 0.69).

“Our finding that the risk of subsequent TRD can be assessed by severity could help clinicians identify at first MDD diagnosis the patients in need of closer follow-up,” Lundberg and colleagues wrote.