Compared With MDD, TRD Associates With Higher Mortality, Intentional Self-Harm

Among patients with MDD, treatment-resistant depression was somewhat frequent and linked with increased rates of self-harm and mortality risk.

A population-based, observational study found that treatment-resistant depression (TRD) was relatively common among patients with major depressive disorder (MDD) and associated with increased rates of self-harm and risk for mortality. These findings were published in JAMA Psychiatry.

Investigators from Karolinska Institutet and Stockholm Health Care Services sourced data for this study from the Stockholm MDD Cohort. Between 2010 and 2017, all patients (N=145,577) in the Stockholm region who met the criteria for MDD were enrolled in the cohort. Incidence of TRD, trends in treatments, and outcomes were evaluated through May 2022. For this study, TRD was defined as 3 or more consecutive antidepressant treatments. To balance for cohort differences, a matching approach between TRD and non-TRD episodes was used.

Among the entire cohort, 110,155 patients had MDD episodes and 12,765 had TRD episodes. The patients with TRD had 12,793 TRD episodes and were matched with 30,380 patients with 62,817 non-TRD episodes. The TRD and non-TRD cohorts comprised patients with median ages of 43.5 (interquartile range [IQR], 32.2-56.2) and 43.4 (IQR, 32.1-55.9) years, 63.4% and 63.9% were women, 64.1% and 64.9% of events were first episodes, and 66.2% and 73.5% were managed by nonpsychiatric health care, respectively.

The median time from an MDD episode to TRD was 552 (IQR, 294-932) days.

The findings show that TRD was associated with higher disease burden with respect to health care resource utilization, lost workdays, intentional self-harm, and mortality and that these findings are not explained by MDD duration.

The group with TRD reported higher rates of other psychiatric comorbidities, including anxiety (59.8% vs 44.4%), stress (35.8% vs 28.0%), and intentional self-harm (4.9% vs 1.8%) compared with the non-TRD group, respectively. To manage depression and other psychiatric conditions, the TRD cohort received more psychotherapy (46.2% vs 34.7%), add-on medications (14.4% vs 4.4%), and electroconvulsive therapy (3.4% vs 0.3%) compared with the non-TRD group, respectively.

In the 12-months prior to and after index date, TRD associated with more outpatient visits (mean, 9.8-11.5 vs 5.6-7.3), inpatient bed-days (mean, 3.9-5.7 vs 1.3-1.7 days), and lost workdays (mean, 132.3-123.9 vs 58.7-70.1 days) compared with the non-TRD group, respectively.

Overall, the patients who proceeded to TRD had 587 different antidepressant treatment sequences. The median time from the start of an MDD episode to first antidepressant treatment was 8 days, from first to second treatment was 165 days, and from second to third treatment was 197 days.

Episodes of TRD were associated with increased risk for all-cause mortality (hazard ratio [HR], 1.23; 95% CI, 1.07-1.41).

On the basis of these trends the investigators formulated a risk score for predicting TRD. The variables self-rated Montgomery-Åsberg Depression Rating Scale, health care type at MDD initiation, outpatient visits in the preceding 12 months, sleep disorder or filling a sedative prescription in previous 3 years, gender, and anxiety or filling anxiolytic prescription in previous 3 years predicted TRD with a C-index of 0.67.

These findings may not be generalizable for populations without access to universal health care.

Study authors concluded, “The findings show that TRD was associated with higher disease burden with respect to health care resource utilization, lost workdays, intentional self-harm, and mortality and that these findings are not explained by MDD duration.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

References:

Lundberg J, Cars T, Lööv SÅ, et al. Association of treatment-resistant depression with patient outcomes and health care resource utilization in a population-wide study. JAMA Psychiatry. Published online December 14, 2022. doi:10.1001/jamapsychiatry.2022.3860