Determinants and Outcomes of Suicidal Behavior Among Patients With Major Depressive Disorder.

Importance: Major depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples. Objective: To describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines. Design, Setting, and Participants: This population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022. Exposures: Patients with MDD with and without records of suicidal behavior. Main Outcomes and Measures: The main outcome was all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated. Results: A total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed. Conclusions and Relevance: This cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.

Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study.

Importance: The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of many observational studies on TRD is limited. Objective: To estimate the burden of 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. Design, Setting, and Participants: This cohort study, a population-based observational study, assessed data from the Stockholm MDD Cohort for episodes of major depressive disorder (MDD) between 2010 and 2017 that fulfilled predefined criteria for TRD (≥3 consecutive antidepressant treatments). Data analysis was performed from August 2020 to May 2022. Main Outcomes and Measures: Outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality, and intentional self-harm and, in the prognostic model, TRD. Results: A total of 158 169 unipolar MDD episodes (in 145 577 patients) were identified between January 1, 2012, and December 31, 2017 (64.7% women; median [IQR] age, 42 years [30-56]). Of these, 12 793 episodes (11%) fulfilled criteria for TRD. The median (IQR) time from the start of MDD episode to TRD was 552 days (294-932). Selective serotonin reuptake inhibitor was the most common class of antidepressant treatment in all treatment steps, and 5907 patients (46.2%) received psychotherapy at some point before initiation of the third pharmacological antidepressant treatment. 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 were all more common comorbid conditions in TRD episodes. Intentional self-harm was more than 4 times more common in TRD episodes. The all-cause mortality rate for patients with MDD with TRD episodes was 10.7/1000 person-years at risk, compared with 8.7/1000 person-years at risk for patients with MDD without TRD episodes (hazard ratio, 1.23; 95% CI, 1.07-1.41). Median time from start of the first antidepressant treatment to start of the second, and from start of the second antidepressant treatment to start of the third, was 165 and 197 days, respectively. The severity of MDD, defined using the self-rating Montgomery-Åsberg Depression Rating Scale (MADRS-S) at time of MDD diagnosis, was found to be the most important prognostic factor for TRD (C index = 0.69). Conclusions and Relevance: In this cohort study, TRD was a common variant of MDD when including patients from both health care types, which is associated with a high disease burden for both patients and society. The median time between initiation of new antidepressant treatments was longer than recommended in current treatment guidelines, suggesting room for more structured and timely depression care.

Clinical and societal burden of incident major depressive disorder: A population-wide cohort study in Stockholm.

OBJECTIVE: Major depressive disorder (MDD) is a highly prevalent condition and a significant contributor to global disability. The vast majority of MDD is handled by primary care, but most real-life studies on MDD only include data from secondary care. The aim of this study was therefore to estimate the total clinical and societal burden of incident MDD including data from all healthcare levels in a large well-defined western European healthcare region. METHODS: Population-wide observational study included healthcare data from Region Stockholm, Sweden's largest region with approximately 2.4 million inhabitants. All patients in Region Stockholm having their first unipolar MDD episode between January 1, 2012, and December 31, 2018, were included. The sample also included matched study population controls. Outcomes were psychiatric and non-psychiatric comorbid conditions, antidepressant therapy use, healthcare resource utilization, work loss, and all-cause mortality. RESULTS: In the study period, 137,822 patients in Region Stockholm were diagnosed with their first unipolar MDD episode. Compared with matched controls, MDD patients had a higher burden of non-psychiatric and psychiatric comorbid conditions, 3.2 times higher outpatient healthcare resource utilization and 8.6 times more work loss. MDD was also associated with a doubled all-cause mortality compared with matched controls (HR: 2.2 [95% CI: 2.0-2.4]). CONCLUSIONS: The high mortality, morbidity, healthcare resource utilization, and work loss found in this study confirms that MDD is associated with individual suffering and low functioning leading to substantial costs for patients and society. These findings should motivate additional efforts in improving outcomes for MDD patients.