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An episode level evaluation of the treatment journey of patients with major depressive disorder and treatment-resistant depression.

ABSTRACT: BACKGROUND:Many patients with major depressive disorder (MDD) fail to respond to antidepressant (AD) pharmacotherapy. The objectives of this study were to characterize MDD and treatment-resistant depression (TRD) at the level of pharmacologically treated episodes and to describe the sequential treatment patterns by lines of therapy (LOT) in the first two episodes. METHODS:Adults (?18 years of age) with continuous enrollment ?12 months before and after the first MDD diagnosis and treated with an AD, with or without an MDD-indicated antipsychotic (AP), were identified (1/1/2010-12/31/2015). The MDD episode started on the date of MDD diagnosis that was preceded by a clean period without any MDD diagnosis. The MDD episode ended on the last MDD diagnosis or the end of the days' supply of AD/AP medication, whichever came last. TRD was defined as an MDD episode with ?3 AD/AP regimens. Measured outcomes included episode duration, number of LOT, relapse hospitalization, and sequential treatment patterns of MDD episode stratified by TRD and non-TRD episodes. RESULTS:Of 48,440 patients who received AD/AP in the 1st MDD episode, 3,317 (6.8%) of episodes were considered TRD. Mean duration of 1st TRD episodes was 571 days, mean number of AD/AP LOTs was 3.47, and 13.7% involved relapse hospitalization. Mean duration of 1st non-TRD episodes was 200 days, mean number of AD/AP LOTs was 1.21, and 9.6% involved relapse hospitalization. Among 1st MDD episodes, 25.5% had a second LOT; 7.3% had a third LOT. Most patients received selective serotonin reuptake inhibitors (SSRIs) as the first LOT (63.0%), and the plurality of regimens were SSRIs in second (44.9%) and third LOT (41.1%). CONCLUSIONS:Compared to non-TRD episodes, TRD episodes were longer and more often involved relapse hospitalizations. SSRIs were the most common treatment; treatment changes and potential treatment unresponsiveness were frequent among MDD patients.

SUBMITTER: Wu B

PROVIDER: S-EPMC6687173 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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An episode level evaluation of the treatment journey of patients with major depressive disorder and treatment-resistant depression.

Wu Bingcao B Cai Qian Q Sheehan John J JJ Benson Carmela C Connolly Nancy N Alphs Larry L

PloS one 20190808 8

<h4>Background</h4>Many patients with major depressive disorder (MDD) fail to respond to antidepressant (AD) pharmacotherapy. The objectives of this study were to characterize MDD and treatment-resistant depression (TRD) at the level of pharmacologically treated episodes and to describe the sequential treatment patterns by lines of therapy (LOT) in the first two episodes.<h4>Methods</h4>Adults (≥18 years of age) with continuous enrollment ≥12 months before and after the first MDD diagnosis and t ...[more]

PMID: 31393922

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Project description:BackgroundTreatment-resistant depression (TRD) refers to patients with major depressive disorder who do not remit after 2 or more antidepressant trials. TRD is common and highly debilitating, but its neurobiological basis remains poorly understood. Recent neuroimaging studies have revealed cortical connectivity gradients that dissociate primary sensorimotor areas from higher-order associative cortices. This fundamental topography determines cortical information flow and is affected by psychiatric disorders. We examined how TRD impacts gradient-based hierarchical cortical organization.MethodsIn this secondary study, we analyzed resting-state functional magnetic resonance imaging data from a mindfulness-based intervention enrolling 56 patients with TRD and 28 healthy control subjects. Using gradient extraction tools, baseline measures of cortical gradient dispersion within and between functional brain networks were derived, compared across groups, and associated with graph theoretical measures of network topology. In patients, correlation analyses were used to associate measures of cortical gradient dispersion with clinical measures of anxiety, depression, and mindfulness at baseline and following the intervention.ResultsCortical gradient dispersion was reduced within major intrinsic brain networks in patients with TRD. Reduced cortical gradient dispersion correlated with increased network degree assessed through graph theory-based measures of network topology. Lower dispersion among default mode, control, and limbic network nodes related to baseline levels of trait anxiety, depression, and mindfulness. Patients' baseline limbic network dispersion predicted trait anxiety scores 24 weeks after the intervention.ConclusionsOur findings provide preliminary support for widespread alterations in cortical gradient architecture in TRD, implicating a significant role for transmodal and limbic networks in mediating depression, anxiety, and lower mindfulness in patients with TRD.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:AimA substantial proportion of major depressive disorder patients are treatment-resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment-resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment-resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment-resistant major depressive disorder.MethodGiven that immune-inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine-related molecules could serve as clinically useful biomarkers of treatment-resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor-α, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy.ResultsThe serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor-α, was significantly higher in treatment-resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment-resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin-6 receptor level measurement was useful for identification of treatment-resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology-Self Report score (QIDS-SR16 ) as a target variable showed that only serum soluble interleukin-6 receptor level could explain the severity of major depressive disorder.ConclusionBased on these results, we recommend measurement of serum soluble interleukin-6 receptor level to discriminate treatment-resistant major depressive disorder patients. High serum soluble interleukin-6 receptor level is associated with the pathogenesis of treatment-resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans-signaling system in onset of treatment-resistant major depressive disorder.

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An episode level evaluation of the treatment journey of patients with major depressive disorder and treatment-resistant depression.

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An episode level evaluation of the treatment journey of patients with major depressive disorder and treatment-resistant depression.

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