Active clinical trials for "Depressive Disorder, Major"

The main aims of the study are to (1) compare the effectiveness of Group metacognitive therapy (GMCT) treatment to that of clinical management and (2) explore patterns of change and investigate factors associated with treatment outcome

The investigators are conducting a randomized controlled trial to evaluate the antidepressant effects of nitrous oxide in people with Major Depressive Disorder (MDD). MDD is a global medical condition that causes significant health and economic burden. Recent studies have shown that a single dose of ketamine, an NMDA-antagonist, has fast and long lasting anti-depressant effect. Nitrous oxide, another NMDA-antagonist, is widely used for anesthesia and analgesia, safer to administer and has fewer side effects than ketamine. A randomized controlled crossover feasibility study showed significant reduction in depressive symptoms at 2 and 24 hours after a single 1-hour treatment session of inhaled nitrous oxide compared with placebo. Nitrous oxide is inexpensive and can be safely administered by any trained clinician. If found to be efficacious, it could be used to provide rapid anti-depressant effect whilst the benefit of traditional anti-depressants has its delayed effect. Another potential application could be in acutely suicidal patients. This investigated-initiated phase 2b trial will enable confirmation and extension of the findings from the feasibility study, and identify the optimal dose and regimen in a broader population of those with MDD. Participants will be randomized to receive a weekly 1-hour inhalational sessions of either nitrous oxide or placebo (oxygen-air mixture) for 4 weeks, and the nitrous group will be further randomly assigned to a dose of 50% nitrous oxide or 25% nitrous oxide. Depression severity will be assessed by a blinded observer pre-treatment and at weekly intervals during and for 4 weeks after treatment using the Hamilton Depression Rating Scale.

A single subanesthetic dose infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and robust antidepressant effects in patients with treatment-refractory major depressive disorder (TRD). A family history of an alcohol use disorder (Family History Positive, FHP) is one of the strongest identified predictors of an improved antidepressant response to ketamine. Like ketamine, alcohol is a functional NMDA receptor antagonist. FHP is associated with differential response to both alcohol, e.g. decreased body sway and plasma cortisol, and ketamine, e.g. blunted psychotomimetic side effects. One of the primary mechanistic hypotheses for ketamine's antidepressant action is the acute intrasynaptic release of glutamate from major output neurons, e.g. cortical pyramidal cells. Preliminary clinical studies have demonstrated this acute glutamate "surge" in response to subanesthetic dose ketamine. Based on these findings, the investigators hypothesize that ketamine's enhanced antidepressant efficacy in FHP TRD subjects is, at least in part, attributable to increased glutamate release relative to TRD subjects without a family history of alcohol use disorder (Family History Negative, FHN). The investigators also hypothesize that alcohol similarly augments glutamate release in this bio- logically-enriched subgroup, which may be a more objective biomarker than family history status. To test these hypotheses, the investigators have designed a now two-site, open-label study of 21-65 year old medically and neurologically healthy, currently moderately-to-severely depressed TRD patients. In total, the investigators plan to recruit 25 FHP and 25 FHN TRD subjects. All subjects must not have a lifetime substance use disorder (except nicotine or caffeine), no lifetime history of an alcohol use disorder and socially drink. The experimental portion consists of two phases. The preliminary first phase is a medication taper (if needed) and psychotropic medication-free period. The experimental second phase comprises two pharmacokinetically-defined basal-bolus alcohol and one subanesthetic dose (0.5mg/kg x 40 minute) ketamine infusions. The first alcohol infusion will establish the pharmacokinetic profile for a subsequent alcohol infusion occurring during 7T-magnetic resonance imaging (MRI), both resting-state functional MRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) to detect glutamate in the ventromedial prefrontal cortex/ventral anterior cingulate cortex (vmPFC/vACC). The ketamine infusion will also occur during 7T-MRI. The primary outcome measure is group mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-ketamine infusion (baseline) to one week post-infusion, where the investigators observed ketamine's greatest antidepressant effect in FHP TRD. Additional outcome measures are vmPFC/vACC glutamate change in response to ketamine and alcohol challenge based on family history status. In summary, this study will provide key mechanistic information on ketamine's improved antidepressant efficacy in a biologically-enriched subgroup. This will contribute to the systematic development of more efficacious, personalized treatments for major depression in an effort to reduce its enormous public health burden.

HYPOTHESIS: Pregnenolone administration will be associated with greater reduction in depressive symptom severity than placebo in women with current mMDD. STUDY AIMS: Primary Aim: Determine if pregnenolone is associated with greater reduction in depressive symptom severity than placebo in women with mMDD, as measured by MADRS. Secondary Aims: Determine if pregnenolone is associated with greater reduction in anxiety symptom severity than placebo in women with mMDD. Determine if pregnenolone is associated with greater improvement in cognition than placebo in women with mMDD. Determine if pregnenolone is associated with greater improvement in quality of life than placebo in women with mMDD. Determine if pregnenolone is associated with greater improvement in vasomotor symptoms of menopause than placebo. Mechanistic Aims: Determine whether changes in neurosteroid levels with pregnenolone mediate clinical response. Determine if baseline neurosteroid levels predict pregnenolone response. Determine whether depressive symptoms, anxiety, sleep or vasomotor symptoms improve first. A crossed-lagged panel model will explore serial correlations between changes in outcome measures.

This study aims at investigating if adjunctive buprenorphine at low dose to treatment as usual is effective in reducing severe suicidal ideas in major depressive episode, and at determining the most effective dose.

Depression has a yearly prevalence superior to 5%, but a 30% of patients cannot benefit of pharmacological treatment, resulting resistant to it. Transcranial direct current stimulation, due to its reduced invasiveness and easy administration showed to be a useful technique to treat these cases, and it is now broadly used in clinical practice. Moreover, thanks to technological advances, this treatment could be self-administered at home, reducing costs and improving scalability. The aim of this study is to confirm the efficacy, safety and feasibility of a home-based intervention for treatment-resistant depression To do this participants will perform a home-based tDCS intervention consisting of 30 minutes sessions, 5 days per week, for 4 weeks. Results should provide critical knowledge regarding home-based therapies for the treatment of resistant depression and evidence on brain mechanisms underlying response to non-invasive brain stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. The investigators are continuing to learn how to optimize outcomes from rTMS treatment. The purpose of this research project is to use brain network connectivity patterns as measured by resting state functional magnetic resonance imaging (fMRI) to confirm a way to optimize the use of rTMS to treat depression. In addition, the study aims to gain a better understanding of how rTMS influences brain networks.

Synopsis Aim: The purpose of the study is to determine the stimulus of electrical current during electroconvulsive therapy (ECT) that produces the optimal balance between antidepressant effect and memory disturbance. Specifically, this study aims to compare the 0.5 ms and 1.0 ms pulse width stimuli. Design: National, register-based randomized trial, unmasked with two treatment arms. Primary objective: To test the hypothesis that a 1.0 ms pulse width stimulus produces a higher remission rate (< 11 on the MADRS-S) than a 0.5ms pulse width stimulus. Secondary objectives include testing for differences in: self-rated global health measured with the EQ5D-VAS subjective memory worsening (increase of 2 on the memory item of the CPRS) antidepressive response (decrease of 50% on the MADRS-S) number of ECTs in the treatment series readmission and suicide rate within 6 months Study population: patients with unipolar or bipolar depression. Sample size: 800 patients, 400 patients in each arm. Inclusion criteria: At least 18 years of age at the time of inclusion Diagnostic criteria fulfilled for unipolar, or bipolar depressive episode according to ICD-10. An indication for and accepting ECT A Swedish personal identity number. Capable of giving informed consent. Exclusion criteria: If the investigator judges a certain pulse width to be inappropriate for the patient. Inclusion time 2019-05-01-2022-11-15. Abbreviations CGI: Clinical Global Impression Scale CPRS: The Comprehensive Psychopathological Rating Scale ECT: Electroconvulsive therapy EQ5D: EuroQual-group 5 Dimensions Scale ICD-10: International Statistical Classification of Diseases and Related Health Problems. - 10th revision, MADRS-S: Montgomery-Åsberg Depression Rating Scale, self assessed version. Q-ECT: Swedish national quality register for ECT VAS: Visual analogue scale

The goal of the study is to address the unmet need of TRD patients by identifying brain networks critical for treating depression and to use next generation precision DBS with steering capability to engage these targeted networks. The study's goal will be achieved through 3 specific aims: Demonstrate device capability to selectively and predictably engage distinct brain networks Delineate depression-relevant networks and demonstrate behavioral changes with network-targeted stimulation Demonstrate that chronic DBS using steered, individualized targeting is feasible and safe for reducing depressive symptoms

This neuroimaging study is a clinical trial investigating the effectiveness of intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to the inferior parietal lobule (IPL) in reducing suicide risk in patients with major depressive disorder (MDD) and borderline personality disorder (BPD).