Active clinical trials for "Depressive Disorder, Major"

The study aim is to explore the effect of a comprehensive Internet-based disease management program for bipolar disorder and recurrent or chronic major depression on clinical outcomes and satisfaction with care.

The neuropeptide Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and its receptors PAC1 and VPAC2 are widely expressed in the nervous system. The investigators found that PACAP treatment of neuronal cell cultures increases expression of Brain Derived Neurotrophic Factor (BDNF) that plays an important role in the etiology of psychiatric disorders and action of antidepressants. For the first time, the investigators demonstrated that treatment by Paroxetine and Citalopram significantly decreases PAC1 and VPAC2 and upregulates PACAP mRNA expression, whereas Imipramine shows an opposite effect. Moreover, PACAP, PAC1 and VPAC2 expression is highly correlated with BDNF expression. Their in vivo studies show that Imipramine reduces BDNF and increases PAC1 mRNA expression in murine hippocampus, suggesting that antidepressants may affect neuronal plasticity through PACAP-BDNF interactions. Based on their observations in experimental systems, the investigators hypothesize that PACAP signaling system may be involved in the etiology of depression and mechanism of antidepressant action. The investigators will evaluate this hypothesis by examining serum PACAP levels, effect of antidepressants on PACAP levels, and gene polymorphisms of PACAP and its receptors in major depressive disorder patients. This study will enhance the investigators' understanding of PACAP's role in the etiology of depression and antidepressant treatment and will provide a basis to evaluate PACAP pathway as a potential target for diagnostics and novel antidepressants drug discovery.

This study examines if Yohimbine, when given during the sleep cycle, will improve symptoms of depression within a matter of hours. Purpose: This study will examine whether the drug yohimbine, given at a specific time during the sleep cycle, produces chemical changes in the brain similar to those that occur with sleep deprivation. It will also see if yohimbine can induce rapid (next day) antidepressant effects in patients with major depression. Total sleep deprivation for 36 hours improves mood in most patients with major depression in a matter of hours, but the response is usually short-lived. Understanding the chemical changes that occur in the body during sleep deprivation may help in the development of a rapidly acting antidepressant.Patients with major depressive disorder between 18 and 65 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, and blood and urine tests. Participants are hospitalized at the NIH Clinical Center for the study, as follows: Drug-free period: Patients are tapered off their anti-depression medications and remain drug-free for 1 week before beginning study phase 1. Study phase 1: Patients undergo sleep deprivation for 36 hours. Those whose depression improves with sleep deprivation initially and then worsens continue to phase 2. The day after sleep deprivation, patients undergo a lumbar puncture (spinal tap). For this test, a local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle. Study phase 2: Patients spend 1 night in the sleep lab. A catheter (plastic tube) is placed in a vein in each arm-one to give yohimbine and the other to draw blood samples. A small monitor cuff is placed on a finger to measure the patient's blood pressure and blood oxygen levels during the night. While asleep, the patient receives a dose of yohimbine or placebo, given over 3 minutes. A lumbar puncture is done the following morning. Patients receive no medications for 6 days, and then the sleep lab procedure is repeated. Patients who received yohimbine in the previous experiment are switched to placebo, and those who were given placebo are switched to yohimbine.

The study will assess the safety, tolerability, and pharmacokinetics of basimglurant compared to placebo after multiple ascending oral doses for up to 22 days in healthy subjects and in patients with MDD on stable selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) background therapy.

The purpose of this study is to evaluate the effects after up to 1 year of supervised weekly Tai-Chi-Chi versus Health Education and Wellness classes on reduction of depressive symptoms and improvement in resilience, health functioning, quality of life, cognition, sleep, fMRI neural correlates of working memory, and brain structure.

The purpose of this study is to examine whether neural-derived exosomal miRNAs are differentially expressed that are specific to suicidal ideation or behavior, and which by affecting specific miRNA targets and pathways, are associated with suicidal behavior and response to ketamine. The following groups of subjects will be examined: 1) major depressive disorder (MDD) with a recent suicide attempt (in past 2 weeks), 2) MDD with serious ideation (in the past 7 days) without recent suicide attempt (in the past 6 months), 3) MDD without clinically significant suicidal ideation (in the past 7 days) or recent suicide attempt (in the past 6 months), and 4) healthy controls. Both suicidal and non-suicidal MDD will be given ketamine (0.5 mg/kg, IV) and blood will be drawn at predose, 30 min, 180 min, 24 hours, and 14 days post-infusion to measure changes in miRNAs. As of May 2022, study is in data analysis. Final outcomes will be known once analysis is complete. As of July 2022, all data collection is complete. The primary and secondary data outcome measure results are complete. The investigators are working on final analysis of the mRNA samples, to provide final responses to questions posed in the Detailed Description section below and listed here: 1) whether suicidal ideation or behavior is associated with differences in the expression of specific miRNAs, 2) whether anti-suicidal/antidepressant effects of ketamine is associated with miRNAs changes, and 3) whether miRNA/mRNA-regulatory pathways contribute to suicide pathogenesis and treatment response.

The main objective of this study is to evaluate the effect of a 12 weeks adapted physical activity program (active walking) on depression by analyzing the dynamics of emotional and cognitive functioning. The secondary objectives are to test the effects of a physical activity on functional performance and to highlight psychological mechanisms.

Objectives To evaluate the safety and tolerability of escalating multiple oral doses of LY03005 in healthy subjects. To characterize the pharmacokinetics of escalating multiple oral doses of LY03005.

This research study is being done to gain a better understanding about brain networks that may be involved in depression. The investigators plan to examine how these networks change after the brain is stimulated with "Transcranial Magnetic Stimulation" (TMS). TMS is a way of stimulating the brain in order to mildly activate or mildly suppress different brain areas, and is used to treat some forms of depression. It is hoped that this study will facilitate learning more about the structure and function of different brain areas and the ways that they are interconnected to form networks, both in depressed people and in people without depression. In this research study, the effects of TMS will be measured by obtaining "pictures" of the brain with "Magnetic Resonance Imaging" (MRI) and with "Positron Emission Tomography" (PET). More specifically, this will be accomplished with a combined MRI and PET scanner, which is capable of simultaneously obtaining both MRI and PET images of the brain. This scanning paradigm will allow the assessment of local metabolic changes resulting from TMS (with PET images) and brain network changes resulting from TMS (with fMRI). Changes resulting from TMS between 20 subjects with depression and 20 healthy volunteers will be calculated and will form the main outcome measure.

Major depression is the leading cause of disability in the United States and is a major contributor to suicide, a leading cause of premature death. The majority of individuals with depression do not receive adequate pharmacologic or psychotherapeutic treatment due to difficulty accessing services or stopping treatment due to side effects, non-response, or the stigma associated with attending mental health clinic visits. Mobile health information technology services, such as text messaging, have the potential to provide effective self-management support for depression to nearly every adult in the US with depression. Guided self-help via text messaging has been shown to be effective for improving a range of health behaviors as well as symptoms of depression. However, previously studied depression text messaging services have not utilized the breadth of psychotherapeutic techniques shown to be effective for depression nor have they attempted to tailor the psychotherapeutic content to the individual in order to improve acceptability and outcomes. Advanced artificial intelligence methods (e.g., reinforcement learning) offers the capability to weed out ineffective messages and to target messages to individuals in order to substantially improve program effectiveness. This pilot study is the first step in towards developing an artificially intelligent text message service for depression. The specific aims of the study are to: 1) demonstrate the feasibility of recruiting and enrolling participants from the general population of US adults and delivering a text-messaging intervention for depression, 2) determine whether there are differences in the perceived helpfulness of messages derived from different psychotherapeutic treatment modalities, and whether these differences are moderated by participant characteristics (e.g., age, gender, depression symptom severity), 3) determine whether messages derived from different psychotherapeutic treatment modalities or their perceived helpfulness are associated with changes in depression symptoms, and whether these relationships are moderated by participant characteristics.