Active clinical trials for "Depressive Disorder"

Background: People with TRD are often helped by electroconvulsive therapy (ECT). But ECT can affect memory and thinking. Researchers want to study a treatment called TEST that uses less electricity. Objective: To study the safety and feasibility of TEST and assess its antidepressant effects. Eligibility: Adults aged 25-64 with major depression that has not been relieved by current treatments. Design: Participants will be admitted to the NIH Clinical Center for 5 18 weeks over 2 3 treatment phases. Their medications may be adjusted. Participants will be interviewed about their depression, side effects, and other treatments they are receiving. They will complete questionnaires. They will give blood and urine samples. Their brain waves and heart rhythm will be recorded. They will take tests of memory, attention, mental functioning, and thinking. Participants will have magnetic resonance imaging (MRI) scans of the head and brain. They will lie on a table that slides in and out of the scanner. Pictures of brain chemicals will also be taken. They may complete tasks during the MRI. Participants will receive TEST and/or sham treatments. They may receive optional ECT. An intravenous catheter will be placed in an arm vein to receive general anesthesia. Two electrodes will be placed on the front of their head. An electric current will be passed from the ECT machine through the electrodes. For sham treatments, they will not receive the electric current. Their breathing, heart rate, brain function, blood pressure, and body movements will be measured. Participants will have 7 follow-up visits over 6 months. Visits can be done via telehealth. Participation will last for up to 42 weeks.

This study is a phase 2/3 open-label controlled trial (CT) in which adults with Major Depressive Disorder (MDD) and adults who have MDD plus comorbid Inflammatory Bowel Syndrome (IBS) will be assigned to either receive oral Fecal Microbiota Transplantation (FMT) or to continue with the treatment they are currently receiving in a Treatment As Usual (TAU) arm. An IBS alone group receiving TAU will be recruited as a clinical control group. The primary goals of this study are to determine effectiveness, safety and tolerability of oral FMT in adults with MDD and in MDD who have comorbid IBS. Additional goals are to characterize patterns and progressions of cognitive and neural correlates associated with MDD and with MDD + IBS and to determine if they improve with FMT. It is known that both, individuals with MDD and those with MDD and IBS show cognitive alterations as well as changes in neural structures, but this study is designed to see if those are changed with treatment response to FMT."

The study is investigating dysfunctions in neurocircuitry in regards to irritability with healthy controls (HC) and individuals with Major Depressive Disorder (MDD) by performing MRIs. The MDD group will also be randomized to receive ketamine or midazolam to investigate changes post-treatment in neurocircuitry with regards to irritability.

Rationale: Opioid misuse and abuse are common problems in the Western world. The rate of unintentional drug overdose is rapidly increasing, not only in the Unites States but also in the Netherlands. Additionally, it is well known that opioids are often used (and abused) in combination with other legal or illicit substances, for example cannabis, including medicinal (i.e. doctor prescribed) cannabis. A major opioid-induced adverse effect is respiratory depression and there are no data that show how oxycodone interacts with cannabis on the ventilatory control system. An appreciable effect is possible given the sedative effects of cannabis. Moreover, investigators previously showed that combining even a low dose of oxycodone (20 mg) with ethanol increased the likelihood of an apneic event (van der Schrier et al. Anesthesiology 2017; 102: 115-122). Because of this side effect and also due to the rising number of addicted chronic opioid users, there is an increasing imminent societal, political and medical interest in advancing research on opioids, opioid-drug interaction and alternatives for the treatment of various chronic illnesses and chronic pain. Hypothesis: The investigators hypothesize that cannabis will amplify the ventilatory depressant effect of oxycodone (primary end-point). Objective: The objective of the study is to quantify the interactive effect of Δ9-tetrahydrocannabinol (THC) and oxycodone on ventilatory control. Study design: Double blind, randomized cross-over, placebo-controlled design. Study population: Healthy human volunteers between the age of 18 and 45 years old. Intervention: Visit A: placebo capsule at t = 0 min + Bedrocan (22.4 mg THC) at t = 90 and 270 min; Visit B: oxycodone 20 mg at t = 0 min + Bedrocan (22.4 mg THC) at t = 90 and 270 min. Main study parameters/endpoints: Primary endpoint: The effect of inhaled THC on ventilation at an end-tidal PCO2 = 55 mmHg without and with concomitant intake of 20 mg oxycodone immediate release (IR) capsule in healthy volunteers 120 min after oxycodone intake. Secondary endpoints: (1) Outcome of Bowdle and Bond & Lader questionnaires; (2) Level of sedation; (3) Pain Pressure Threshold; (4) slope of the hypercapnic ventilatory response; (5) plasma concentrations of THC, 11-OH-THC and oxycodone; a secondary analysis will be performed on the pharmacokinetic and pharmacodynamic data (PKPD modeling).

During the past three decades, researchers have paid particular attention to the study of olfactory disorders in depression. Recent studies have shown that depression is characterized by a change in olfactory and emotional perception resulting in a decrease of the perception of positive stimuli (odors and facial expressions) and an increase in perception of negative stimuli (odors). Moreover, it has also been shown in healthy subjects that the presence of minor depressive symptoms leads to a decreasing of olfactory sensitivity. However, odor discrimination was not impaired in these subjects. This observation suggest the presence of a change in "targeted" olfactory perception in people with depressive symptoms without reporting major depression. In addition, studies in subjects with olfactory disorders (following respiratory tract infections or following Parkinson's disease) have shown an improvement in olfactory function after daily training with odors during 12 weeks. From all these observations, the hypothesis is that an olfactory training could improve the overall olfactory functioning and the emotional perception of the subjects presenting minor depressive symptoms and of the depressed patients.

LPS Challenge in Individuals with Major Depressive Disorder

Depression is a leading cause of burden in Canada and globally. Although more people now seek and receive treatment for depression, there are still many who do not respond well to treatments. New and low-cost options are needed to improve the lives of people with depression. Research suggests that asking patients to complete questionnaires and sending feedback to their clinicians may improve depressive symptoms. Research also shows that encouraging individuals with depression to take part in shaping their own care can be beneficial. To date, no research has examined a combination of these two approaches. This project aims to investigate the benefits of providing personalized feedback to patients and clinicians in order to improve the care and outcomes for people with depression in Canada. To answer this research question, adults who are diagnosed with depression will be placed in one of two groups: 1. The patient and clinician will receive feedback to help guide further care based on the patient's responses to questionnaires 2. The patient and clinician will not receive feedback. The feedback form has been developed with input from clinicians, researchers and people with lived experience of depression, and follows new Canadian treatment guidelines. Information including depressive symptoms, quality of life, personal goals for recovery, and healthcare costs will be collected for a year or longer using an online data collection platform. The research team includes clinician-scientists, healthcare managers, educators, primary care physician and people with lived experience of depression. This project has the potential to deliver significant health benefits for individuals with depression, lessen the population burden of depression and improve the health care system by optimizing care delivery and improving quality of life at low cost.

Late-life depression is a significant public health concern, and effective interventions for prevention and treatment are needed. Insomnia and inflammation are modifiable targets for depression prevention, and this study is significant in using an experimental approach (i.e., inflammatory challenge) to probe acute inflammatory- and depression responses as a function of insomnia, which will inform identification of molecular targets for pharmacologic interventions, and improvement of insomnia treatments to prevent depression in older adults. Project

This study will identify the sex-dependent impact of expiratory-gated transcutaneous vagus nerve stimulation (tVNS) on the modulation of the stress response circuitry and associated physiology in major depressive disorder (MDD). We will evaluate a sample of 80 adults with recurrent MDD randomized to receive active or sham expiratory-gated tVNS during a functional magnetic resonance imaging (fMRI) session, with simultaneous mood and physiological assessments. We hypothesize that expiratory-gated tVNS will effectively modulate, in a sex-dependent manner, specific brainstem-cortical pathways of the stress circuitry and attenuate physiological deficits in MDD.

The central goal of this application is to demonstrate the causal contribution of reward learning signals (expected values and reward prediction errors [RPE]) to antidepressant responses (Aim1) by experimentally manipulating expected values using transcranial magnetic stimulation (TMS) targeting the vmPFC (Aim 2) and μ-opioid striatal RPE signal using pharmacological approaches (Aim 3).