Active clinical trials for "Depressive Disorder, Treatment-Resistant"

An open-label, multi-centre, Phase 2a study to evaluate the safety, tolerability and pharmacodynamics after a single intranasal dose of BPL-003 combined with psychological support, in patients with treatment resistant depression not currently taking antidepressants.

The purpose of this study is to compare the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) conducted over 16 weeks (acute and continuation treatment) with Behavioral Activation (BA; same dose and duration) in persistently depressed treatment-resistant inpatients regarding efficacy, moderators and mediators of change.

Major depressive disorder (MDD) is a common and troublesome disorder, with high risk of physical and psychiatric comorbidity. At least one-third of patients could not achieve a response after several antidepressant trials, so-called treatment-refractory depression (TRD). The high-frequency repetitive transcranial magnetic stimulation (rTMS) or intermittent theta-burst stimulation (iTBS) at left-sided dorsolateral prefrontal cortex (DLPFC) have a response rate of 40-60%. Obviously, not all TRD patients achieve the remitted state after treatment with antidepressants or DLPFC-rTMS, which may result from the heterogeneity of MDD. More and more evidence, such as brain lesion studies, deep brain stimulation, open-labeled rTMS case series, and neuroimaging studies, suggests that dorsomedial prefrontal cortex (DMPFC) might play a more central role in the pathophysiology of major depression. The DMPFC demonstrated as a "dorsal nexus" phenomenon in depression, which means a unique brain region where cortical networks for affect regulation, default mode control and cognitive control coverage in depressed subjects but not in healthy persons. In addition, another meta-analysis of resting-state functional MRI (fMRI) demonstrated the abnormal functional connectivity from DMPFC. These abnormalities of networks were highly associated with several depressive symptoms such as anhedonia, emotional regulation, somatic markers, rumination, self-reflection, poor attention and poor decision-making. However, only a handful of studies investigated the brain stimulation targeting DMPFC and the further changes in brain functional connectivity. The clinical efficacy and the fMRI changes of prolonged intermittent theta-burst stimulation (piTBS) and 20Hz- rTMS targeting bilateral DMPFC were investigated, and the predictive value of baseline networks by fMRI for antidepressant responses was also assessed to find a reliable approach to gauge treatment response prospectively.

The aim is to apply an exercise program to study symptomatic and physical changes, as well as to evaluate the improvement in functionality in a resistant depression unit. Sample: 20 patients with the resistant major depressive disorder who will undergo an exercise program. Before and after 12 weeks of intervention, the participants will be assessed with clinical, physical, physiological, biochemical, and functional variables. During 3 months the exercise program will be implemented 2 days per week. It is expected to find an improvement in mood and functionality, as well as changes in physical areas such as blood pressure or body mass index, which are considered predictive factors of cardiovascular disease.

Resistant Depression is a common condition in older adults and there is an urgent need for novel antidepressant in this population. Nitrous Oxide (N2O) has recently shown rapid antidepressant effect in midlife depression but no study has currently investigated the efficacy and safety of N2O in Late-Life Depression (LLD), while N2O may prove to be an ideal treatment for LLD because of glutamatergic antagonism and cerebrovascular effects and also a relatively good safety profile. The goal of our study is to compare changes in depressive symptoms after 2 hours, 24 hours, 1 week and 2 week of a 1-hour exposure to EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide) versus Medical Air. Secondary Objectives include comparing differences in neuroimaging measures between 3 groups (responders and non-responders in the EMONO group, and patients in the control group).

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.

The studies will be conducted in parallel at two sites: the the Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai (MSSM), and Stanford Depression Research Clinic at Stanford University School of Medicine (SUSM). In addition, MRI studies for the MSSM patients will be carried out at the New York State Psychaitric Institute (NYSPI). The following procedures will be approved by the local Institutional Review Boards (IRBs) at each site, where the site PIs (Alla Landa, PhD, NYSPI, James Murrough, MD at MSSM, and Alan Schatzberg, MD at SUSM) will be responsible for overseeing conduct of the study at their respective site. Dr. Jonathan Javitch is the scientific leader of this program and holds the IND for tianeptine use in this study. Investigators will recruit 75 participants with current unipolar MDD, non-delusional, between 21-60, who have failed at least 2 two adequate treatment trials with a standard antidepressant. Patients will receive an 8-week treatment trial of tianeptine. MSSM patients will also undergo structural and task-based magnetic resonance imaging (MRI) that will be performed under Dr. Landa's direction at NYSPI in order to maintain the internal validity of the data set. MSSM subjects will be transported to NYSPI to complete neuroimaging procedures as described below. Participants will be screened for MRI clearance during their screening visit and again at NYSPI on the day of the scan. Subjects will be asked MRI screening questions to ensure that are scanning eligible. Participants will also have additional tubes of blood drawn for human whole-genomic testing. This microarray will be used to identify regions of the human genome that contribute to disease susceptibility and phenotypes. The Illumina human whole-genome array will be used to provide a comprehensive view of the genome, detects single nucleotide polymorphisms and other variations across the genome.

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.

The purpose of this study is to compare the effects on depressive symptoms of subjects who discontinue serotonergic antidepressants (a certain type of antidepressant, such as Prozac, that works on serotonin receptors in the brain) with the effects on depressive symptoms of subjects who continue to take serotonergic antidepressants. During this study, subjects will also be presented with the opportunity to undergo genetic testing for the serotonin gene transporter which has a short or long form. This is being done because it has been demonstrated that genetic testing improves outcome while treating treatment-resistant depression.

Major depressive disorder (MDD) is a leading cause of disability worldwide. Up to 50% of patients experience treatment resistant depression (TRD), which accounts for a vast majority of disease burden. Current medications for TRD have limited efficacy and can be associated with intolerable side effects. Therefore, there is a need for finding new treatment targets. Accumulating evidence suggests some patients with MDD including those with TRD, display brain inflammation. Thus, patients with TRD may benefit from medications that can reduce this inflammation. Minocycline is an antibiotic which can cross the blood-brain barrier and has effects on several systems implicated in depression. The principal investigator led the first pilot study of minocycline as an add-on treatment in TRD demonstrating that it led to a significant reduction in depressive symptoms compared to placebo and these findings require replication in a larger sample to confirm the efficacy and tolerability of this treatment approach. This study is a 12 week, double-blind, placebo-controlled trial of minocycline as add-on treatment for patients suffering from a major depressive episode who have failed to respond to antidepressant treatment, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5) and the Antidepressant Treatment History Form (ATHF) at screening. After screening and randomization to the two parallel arms of the trial, 50 patients will receive minocycline added to treatment as usual (TAU) and 50 patients will receive placebo added to TAU. Clinical assessment will include the Hamilton Depression Rating Scale (HRSD-17), Clinical Global Impression scale (CGI), World Health Organization Quality of Life Short Form (WHOQOL-BREF), and Generalized Anxiety Disorder scale (GAD-7), administered at each study visit (baseline, week 2, 6, and 12). Side effects checklists will be undertaken at each visit. Minocycline will be started at 100 mg once daily and will be increased to 100 mg twice daily at two weeks. Secondary outcomes include inflammatory biomarkers measured at baseline, weeks 6 and 12. This trial will provide further evidence of minocycline's efficacy and acceptability as a treatment option for patients with TRD and provide insights into its mechanism of action.