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

Abstract

ImportanceThe 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.ObjectiveTo 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 ParticipantsThis 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 MeasuresOutcomes 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.ResultsA 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 RelevanceIn 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.

Sleep Quality After Quetiapine Augmentation in Patients With Treatment-Resistant Depression and Personality Disorders

“…47 Although PD is among the most common comorbid psychiatric conditions in TRD, none of these studies reported on participants with both TRD and PD. [48][49][50] Our study supports previous studies showing that a pharmacotherapy including quetiapine can improve subjective sleep in TRD independently of the presence of PD or not. However, we found a greater improvement of sleep quality in TRD/PD+ compared with TRD/PD− treated with a pharmacotherapy, which included quetiapine.…”

“…In a 20-week open trial with quetiapine (315 ± 109 mg, flexible dose), 14 patients with TRD showed a decrease of more than 4 points on the TSS at their first time of measurement (eg, after only 2 weeks of treatment) 47 . Although PD is among the most common comorbid psychiatric conditions in TRD, none of these studies reported on participants with both TRD and PD 48–50 . Our study supports previous studies showing that a pharmacotherapy including quetiapine can improve subjective sleep in TRD independently of the presence of PD or not.…”

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

“…Moreover, results of a recent analysis in the WHO World Mental Health Surveys underscores that persistence with next-step treat ments is uncommon in persons with MDD 82 . Also, in those who do switch to nextstep treat ments, a considerable treatment delay (i.e., 6-9 months) elapses before switching occurs 82,83 .…”

A 6-week, phase IIb, randomized, double-blind, placebo-controlled trial of Anyu Peibo capsules for the treatment of major depressive disorder in adults

“…The exclusion criteria mainly included the following: (1) subjects who had a suicide attempt within the last year, a currently significant risk of suicide, or a score ⩾3 points on Item 3 (suicide assessment) of the HAMD-17; (2) subjects with a current psychiatric diagnosis other than depression; (3) subjects with unstable cardiovascular, hepatic, renal, blood, endocrine, or other medical diseases; (4) subjects with any neurological disease (such as Parkinson's disease, cerebrovascular accident and epilepsy) or cerebral injury (traumatic or diseaserelated injury); (5) subjects with clinically significant abnormal laboratory values; (6) subjects who used at least two different antidepressants with the recommended dose and an adequate duration of treatment (maximum dosage for at least 4 weeks journals.sagepub.com/home/tpp TherapeuTic advances in psychopharmacology according to the label) and still had no response; (7) subjects who had received regular antidepressant treatment in the 2 weeks prior to screening; (8) subjects who received electroconvulsive therapy (ECT), transcranial magnetic stimulation, or other physical therapy within 3 months; (9) subjects who had a history of substance abuse (including alcohol, drug or other psychoactive substance abuse) within 1 year before screening; and (10) women who were pregnant, breastfeeding, or serum human chorionic gonadotropin (HCG) (+) on screening or were planning to become pregnant. A more detailed list of the inclusion/ exclusion criteria can be found at http://clinicaltrials.gov (NCT03183505).…”

“…However, despite the availability of antidepressants in multiple classes, almost one-third of MDD patients do not respond to conventional antidepressant medications. 4,5 Thus, there is an urgent need to develop novel treatments for MDD.…”