TRD Can Increase Mortality and Comorbidity Rate, Study Finds

Patients with treatment-resistant depression (TRD) were found to have a 23% higher all-cause mortality rate and a higher likelihood of comorbidities than patients with major depressive disorder (MDD), according to study findings published in JAMA Psychiatry.

Clinicians should more frequently replace treatments that aren’t working for patients, lead author Johan Lundberg, MD, PhD, professor of psychiatry at the Karolinska Institute, recommends.

“We’re talking about a patient group with a substantial health care consumption that might be identified earlier than today by increasing the use of symptom severity rating scales,” Dr Lundberg said in a news release. “Going by the results of the study, their care and treatment could be improved if their physician replaced ineffective treatments more rapidly and more often used treatments recommended for treatment resistant depression, such as lithium, than was the case in the study material.”   

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This cohort study analyzed population information from residents in Stockholm, Sweden, who had episodes of MDD from 2010 to 2018. Patients that fit the criteria for TRD—3 or more consecutive antidepressant treatments—were identified. All patients had access to universal health care at the time of treatment.

A total of 158,169 MDD episodes in 145,577 patients were identified with 12,793 episodes—or 11%—meeting the criteria for TRD. When compared with matched non-TRD episodes, TRD episodes had, on average, 3.9 more inpatient bed-days, 132 more lost workdays, and 4 times the risk of self-harm. The mortality rate for patients with TRD was 10.7/1000 person-years at risk versus 8.7/1000 person-years at risk for patients without TRD. MDD severity was found to be the most important prognostic factor for TRD (C index = 0.69), measured by the self-rating Montgomery-Åsberg Depression Rating Scale (MADRS-S).

Researchers also found a median time of 552 days from the beginning of the MDD episode to the diagnosis of TRD.

“The long duration from MDD diagnosis until TRD suggests that clinicians could improve their alignment to recommendations of timely follow-up of patient symptoms,” noted Dr Lundberg. “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 J, Cars T, Lööv S, et al. Association of treatment-resistant depression with patient outcomes and health care resource utilization in a population-wide study. JAMA Psych. 2022. doi:10.1001/jamapsychiatry.2022.3860

Patients with treatment resistant depression at higher risk of death. News release. EurekAlert! December 14, 2022. Accessed January 4, 2023.