Experimental Therapies for Treatment-Resistant Depression: "How do you decide when to go to an unproven or experimental therapy with patients that are treatment-resistant depression?"
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ABSTRACT:
SUBMITTER: Jha MK
PROVIDER: S-EPMC6103647 | biostudies-literature |
REPOSITORIES: biostudies-literature
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2013-03-29 | E-GEOD-45603 | biostudies-arrayexpress
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Project description:This study aimed to elucidate the transcriptional differences in peripheral blood mononuclear cells (PBMC) between individuals with treatment-resistant depression (TRD) and a control group without a psychiatric illness; and between patients with TRD, treated with either standard antidepressant drugs alone, or in combination with electroconvulsive therapy (ECT) or ketamine. Additionally, PBMC transcriptomics were compared between treatment responders, following completion of their treatment protocols. PBMC transcriptomics were compared between treatment responders, following completion of their treatment protocols.
2024-06-30 | GSE234669 | GEO
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2013-04-01 | GSE45468 | GEO
Project description:Importance:There is an unmet need for effective treatments for suicidality in mental disorders. Magnetic seizure therapy (MST) has been investigated as an alternative to electroconvulsive therapy, a known effective treatment for suicidality, in the management of treatment-resistant major depressive disorder, with promising findings. Yet, there are very limited data on the association of MST with suicidality directly. It is important to explore the potential of MST as a viable treatment alternative to electroconvulsive therapy for suicidality. Objective:To determine the association of MST with suicidality in patients with treatment-resistant major depressive disorder. Design, Setting, and Participants:This nonrandomized controlled trial took place at a single tertiary care psychiatric facility in Canada. It followed an open-label study design with consecutive treatment cohorts. Consecutive groupings of 67 patients with treatment-resistant major depressive disorder and with baseline suicidality present were treated for up to 24 treatments. The study was run from February 2012 through June 2019. Patients were followed up for 6 months at the end of the treatment period. This post hoc secondary analysis of the trial was performed from January to November 2019. Interventions:MST was delivered at 100% stimulator output over the prefrontal cortex with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency, for a maximum of 24 sessions. Main Outcomes and Measures:Remission from suicidality was measured as an end point score of 0 on the Beck Scale for Suicidal Ideation. A linear mixed model was used to assess the trajectory of Beck Scale for Suicidal Ideation scores. Results:A total of 67 patients (mean [SD] age, 46.3 [13.6] years; 40 women [60.0%]) received a mean (SD) of 19.5 (5.1) MST treatments. The overall number of patients achieving remission was 32 (47.8%). Sixteen patients (55.2%) receiving low-frequency MST achieved remission, as well as 12 patients (54.5%) in the moderate-frequency group, and 4 patients (25.0%) in the high-frequency group. The linear mixed model revealed an association of time with Beck Scale for Suicidal Ideation scores (F8,293.95?=?5.73; P?<?.001). Conclusions and Relevance:These findings suggest that MST may be an effective treatment for suicidality, and sensitivity analysis shows this may be particularly so at low and moderate frequencies. Future studies should directly compare MST with electroconvulsive therapy for treating suicidality and should evaluate MST as a treatment for suicidality across mental disorders. Trial Registration:ClinicalTrials.gov Identifier: NCT01596608.
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Project description: Not available
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Project description:To further explore predictors and targets of response to infliximab, differential gene expression was examined at baseline and after 6 and 24 hours and 2 weeks after the first infusion of infliximab in TRD patients who were infliximab responders versus nonresponders, and compared to placebo-treated patients. In a recent clinical trial, the TNF antagonist infliximab was found to reduce depressive symptoms compared to placebo but only in patients with increased inflammation as reflected by a CRP >5 mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined at baseline and after 6 and 24 hours and 2 weeks after the first infusion of infliximab in TRD patients who were infliximab responders versus nonresponders, and compared to placebo-treated patients.
2013-04-01 | E-GEOD-45468 | biostudies-arrayexpress
Project description:BackgroundChronic and treatment-resistant depressions pose serious problems in mental health care. Mindfulness-based cognitive therapy (MBCT) is an effective treatment for remitted and currently depressed patients. It is, however, unknown whether MBCT is effective for chronic, treatment-resistant depressed patients.MethodA pragmatic, multicenter, randomized-controlled trial was conducted comparing treatment-as-usual (TAU) with MBCT + TAU in 106 chronically depressed outpatients who previously received pharmacotherapy (≥4 weeks) and psychological treatment (≥10 sessions).ResultsBased on the intention-to-treat (ITT) analysis, participants in the MBCT + TAU condition did not have significantly fewer depressive symptoms than those in the TAU condition (-3.23 [-6.99 to 0.54], d = 0.35, P = 0.09) at posttreatment. However, compared to TAU, the MBCT + TAU group reported significantly higher remission rates (χ2 (2) = 4.25, φ = 0.22, P = 0.04), lower levels of rumination (-3.85 [-7.55 to -0.15], d = 0.39, P = 0.04), a higher quality of life (4.42 [0.03-8.81], d = 0.42, P = 0.048), more mindfulness skills (11.25 [6.09-16.40], d = 0.73, P < 0.001), and more self-compassion (2.91 [1.17-4.65], d = 0.64, P = 0.001). The percentage of non-completers in the MBCT + TAU condition was relatively high (n = 12, 24.5%). Per-protocol analyses revealed that those who completed MBCT + TAU had significantly fewer depressive symptoms at posttreatment compared to participants receiving TAU (-4.24 [-8.38 to -0.11], d = 0.45, P = 0.04).ConclusionAlthough the ITT analysis did not reveal a significant reduction in depressive symptoms of MBCT + TAU over TAU, MBCT + TAU seems to have beneficial effects for chronic, treatment-resistant depressed patients in terms of remission rates, rumination, quality of life, mindfulness skills, and self-compassion. Additionally, patients who completed MBCT showed significant reductions in depressive symptoms. Reasons for non-completion should be further investigated.
| S-EPMC6175087 | biostudies-literature
Project description:The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is associated with rapid but transient antidepressant effects in patients with treatment resistant unipolar depression (TRD). Based on work suggesting that ketamine and lithium may share overlapping mechanisms of action, we tested lithium compared to placebo as a continuation strategy following ketamine in subjects with TRD. Participants who met all eligibility criteria and showed at least an initial partial response to a single intravenous infusion of ketamine 0.5 mg/kg were randomized under double-blind conditions to lithium or matching placebo before receiving an additional three infusions of ketamine. Subsequent to the ketamine treatments, participants remained on lithium or placebo during a double-blind continuation phase. The primary study outcome was depression severity as measured by the Montgomery-Åsberg Depression Rating Scale compared between the two groups at Study Day 28, which occurred ~2 weeks following the final ketamine of four infusions. Forty-seven participants with TRD were enrolled in the study and underwent an initial ketamine infusion, of whom 34 participants were deemed to have at least a partial antidepressant response and were eligible for randomization. Comparison between treatment with daily oral lithium (n = 18) or matching placebo (n = 16) at the primary outcome showed no difference in depression severity between groups (t32 = 0.11, p = 0.91, 95% CI [-7.87, 8.76]). There was no difference between lithium and placebo in continuing the acute antidepressant response to ketamine. The identification of a safe and effective strategy for preventing depression relapse following an acute course of ketamine treatment remains an important goal for future studies.
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