Clinical Research Directory

Natural History of Depression, Bipolar Disorder and Suicide Risk

Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide. People 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254. This study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time. Participants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation....

NQ Square TMS for Major Depressive Disorder: One Day, Three Sessions in Adults

Transcranial Magnetic Stimulation (TMS) Therapy is a non-invasive procedure that uses magnetic pulses to stimulate the cortex (brain) to treat Major Depressive Disorder (MDD). Currently established therapy uses one 19-minute treatment session per day for 5 days per week for 6 weeks, for a total of 30 treatment sessions. The goal of this multi-site sham-controlled double-blinded randomized clinical trial is to evaluate the safety and effectiveness of accelerating the delivery of the NeuroQore Square TMS system's rectangular waveform rTMS protocol for the treatment of adults aged 22-85 with Major Depressive Disorder. The accelerated protocol of this study will involve the same currently FDA-cleared 19-min treatment session offered three times in a single day, with no additional treatment sessions.

Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

This is a multicenter, randomized, double-blind, placebo-controlled parallel-group, fixed-dose study in patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing ADT.

Evaluation of the Impact of the EDIT-B® Blood Test on the Health Status of Patients Presenting a Major Depressive Episode. Clinical Utility and Medico-Economic Aspects

Depression is one of the most common mental disorders, affecting nearly 10% of men and 20% of women worldwide. It is associated with a significant increase in mortality, mainly due to suicidal behavior. The Diagnostic and Statistical Manual of Mental Disorders (DSM) defines a Major Depressive Episode (MDE) by a combination of at least five different symptoms, with at least one depressed mood or loss of interest. MDEs can occur in isolation or as part of Major Depressive Disorder (MDD) or bipolar disorder (BD). Bipolar disorders affect 2% of the world's population and are defined by episodes of mania (Type I BD) or hypomania (Type II BD) alternating with episodes of depression and periods of remission. Depression occurring whether in the context of BD or MDD is defined with the same clinical criteria. However, the pharmacological treatments are different in the two groups. In particular, antidepressants prescribed without a thymoregulator in bipolar patients can lead to a worsening of the episode, favoring suicidal behavior or a manic turn. The average interval between the onset of BD symptoms and appropriate diagnosis is estimated to be approximately 7 years, which delays appropriate management and treatment and increases the risk of suicide. Biological markers able to differentiate between the different types of depression were lacking before the advent of EDIT-B®; one of the main objectives of this research is to measure the clinical impact of the use of EDIT-B® in the short and medium term on the management of patients with BD and major depression. The health economic aspect will also be considered. In total, 450 patients in two different groups (EDIT-B® group and control group) will be recruited over a study timeline of 24 months. Study participation is over 6 months with 4 visits.

Defining Neurobiological Links Between Substance Use and Mental Illness

Background: Nicotine dependence leads to about 480,000 deaths every year in the United States. People with major depressive disorder (MDD) are twice as likely to use nicotine compared to the general population. They have greater withdrawal symptoms and are more likely to relapse after quitting compared with smokers without MDD. More research is needed on how nicotine affects brain function in those with MDD. Objective: To understand how nicotine affects symptoms of depression and related brain function. Eligibility: People aged 18 to 60 years, at the time of consent, with and without MDD who do not smoke cigarettes or use other nicotine products. Design: Participants will have 2 or 3 study visits over 1 year. Participants will have 2 MRI scans no less than 4 days apart. Each scan visit will last 5 to 7 hours. At each scan, they will have urine and breath tests to screen for recent use of alcohol, nicotine, and illegal drugs. Before each scan, they will take 1 of 2 medications: nicotine or placebo. Participants will receive each medication once. They will not know which medication they are receiving at each scan. For each MRI scan, they will lie on a table that slides into a cylinder. Sometimes they will be asked to lie still. Sometimes they will complete tasks on a computer. Tasks may include identifying colors or playing games to win money. Each scan will take about 2 hours. Participants will answer questions about their thoughts, feelings, and behaviors before and after each scan. They will have a blood test after each scan.

Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders

Study Description: This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neuro-cognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points. Primary Objectives: To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli. Secondary Objectives: 1. To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. 2. To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. 3. To document relations among broad arrays of clinical, cognitive, and neural measures Primary Endpoints: Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm. Secondary Endpoints: 1. Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. 2. Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli. ...

Behavioral and Neuronal Correlates of Human Mood States

Optimizing treatments in mental health requires an easy to obtain, continuous, and objective measure of internal mood. Unfortunately, current standard-of-care clinical scales are sparsely sampled, subject to recency bias, underutilized, and are not validated for acute mood monitoring. The recent shift to remote care also requires novel methods to measure internal mood. Recent advances in computer vision have allowed the accurate quantification of observable speech patterns and facial representations. The continuous and objective nature of these audio-facial behavioral outputs also enable the study of their neural correlates. Here, the investigators hypothesize that video-derived audio-facial behaviors have discrete neural representations in the limbic network and can provide a critical set of reliable longitudinal estimates of mood at low cost across home and clinic settings.

Dupilumab in Major Depressive Disorder

This study aims primarily to test target engagement of dupilumab by assessing changes in peripheral immune markers following interleukin-4 receptor alpha (IL-4Rα) blockade in adults with major depressive disorder (MDD). Secondary aims include evaluating safety, tolerability, feasibility, and open-label effects on depressive symptoms, blood-based immune markers, blood-brain barrier (BBB) function, and functional brain reward circuitry.

Regulated Stimulation for Optimized Network Activity and Therapeutic Equilibrium

The objective of this study is to evaluate the safety, tolerability, and preliminary efficacy of the Motif eXternally powered Cortical Stimulation (XCS) System when used as indicated for treatment-resistant depression (TRD).

Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy

This protocol proposes an initial randomized clinical trial that includes all patients with suicidal ideation (SI) at baseline, and with SI as the primary outcome measure to examine whether Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) treatment has more magnitude and rate of remission of SI as conventional pulse amplitude Right Unilateral Electroconvulsive Therapy (RUL ECT) (based on our prior secondary analysis). Our central hypothesis is that RUL LAP-ST has significantly less cognitive/memory side effects (no memory side effects were noted in our prior studies for 500mA and 600mA) and thus is more favorable in terms of side effects compared to RUL conventional pulse amplitude ECT, while maintaining better anti-suicidal effect.

Long-Term Study to Assess the Safety and Tolerability of NBI-1065845 as an Adjunctive Treatment in Participants With Major Depressive Disorder (MDD)

This study will evaluate the long-term safety and tolerability of NBI-1065845 as an adjunctive treatment in participants with MDD.

Neurostructural and Biochemical Signatures of Tobacco Smoking in Mood Disorders

Tobacco smoking is significantly more common among individuals with mood disorders, such as major depressive disorder (MDD) and bipolar disorder, compared to the general population. Chronic smoking in these conditions is often linked to more severe symptoms, frequent episodes, and reduced overall quality of life. However, the biological mechanisms linking tobacco smoking to brain alterations and clinical outcomes in mood disorders remain incompletely understood. The primary purpose of this study is to examine whether chronic tobacco cigarette smoking is associated with alterations in brain structure, specifically regional brain volumes including the hippocampus and insula, and circulating biochemical markers of neuronal injury (neurofilament light chain \[NfL\]) and neurobiological pathways (tryptophan and kynurenic acid). The study will enroll 240 male participants aged 18 to 45 years across six equal groups: 1. Major depressive disorder (in remission) who are current smokers 2. Major depressive disorder (in remission) who are lifetime never-smokers 3. Bipolar disorder who are current smokers 4. Bipolar disorder (in remission) who are lifetime never-smokers 5. Healthy controls who are current smokers 6. Healthy controls who are lifetime never-smokers Participants will take part in a single study visit involving: * Clinical assessments and psychiatric rating scales evaluating mood symptoms, cognition, personality traits, and smoking history. * Routine physical and vital sign measurements. * A fasting morning blood draw to evaluate serum biomarkers (NfL, tryptophan, kynurenic acid) and confirm tobacco exposure via serum cotinine. * A structural brain magnetic resonance imaging (MRI) scan to measure regional brain volumes.

Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression

Background: Most drugs that treat mood disorders take a long time to work. Ketamine works within hours. A dose can last for a week or more. Certain receptors in the brain might help ketamine work. A drug that blocks these receptors might affect how it works. Objective: To see if the antidepressant response of ketamine is linked to AMPA receptors. Eligibility: Adults ages 18-70 with major depression disorder without psychotic features Design: Participants will be screened under protocol 01-M-0254. They will have blood tests and a physical exam. Participants will stay at the NIH Clinical Center for 5 weeks. Phase 1 lasts 4 weeks. For 2 weeks, participants will taper off their psychiatric medicine. Then they will have the following tests: * Blood draws * Psychological tests * MRI: Participants will lie in a machine that takes pictures of their brain. * MEG: Participants will lie down and do tasks. A cone lowered on their head will record brain activity. * Optional sleep tests: Electrodes on the scalp and body and belts around the body will monitor participants while they sleep. * Optional TMS: Participants will do tasks while a wire coil is held on their scalp. An electrical current will pass through the coil that affects brain activity. For phase 2, on day 0 participants will take the study drug or a placebo orally. While having a MEG, they will get ketamine infused into a vein in one arm while blood is drawn from a vein in the other arm. On day 1, participants will again take the study drug or a placebo orally. On days 3-7, they will repeat many of the phase 1 tests. Days 8 and 9 are optional and include an open label ketamine treatment and many of the phase 1 tests.

SMART Trial to Predict Anhedonia Response to Antidepressant Treatment

The main goal of this research is to use behavioral, brain, and clinical data to determine which type of antidepressant might be optimal before people with depression start treatment.

Impact of Psychomotor Therapy on the Quality of Life in Depression

The effectiveness of psychomotor therapy in improving clinical outcomes or quality of life for individuals with depression is unclear. The investigators will assess how the participants' quality of life and psychomotor profile change over time. The study aims to compare the quality of life at 3 months between patients who received 3 months of personalised psychomotor therapy in addition to standard treatment and those who received standard treatment alone. The study lasted for 6 months, and the investigators expects a total of 128 people to participate in this research across several hospital establishments. This study evaluates the effectiveness of two types of treatment, divided into two randomly selected groups. To participate, individuals must have a medical diagnosis of major depressive disorder (MDD) and be between the ages of 20 and 60. They must have depressive symptoms with an HDRS score greater than 16 and provide informed consent. They must be treated or hospitalised at the Centre Hospitalier Esquirol or the Centre Hospitalier Henri Laborit (France). After providing consent, they will undergo an initial clinical interview that evaluates anxiety, self-esteem, pleasure, and quality of life. The therapist assessed the participant's muscle tone, gross motor skills, praxis, manual dexterity, rhythm, processing of sensory information, and body image. Following the assessment, the participant was randomly assigned to either the experimental or control group. The experimental group received the usual treatment for depression and underwent psychomotor therapy once a week for 12 weeks. The control group received the standard treatment for depression and underwent weekly telephone interviews. An assessment is scheduled at 1 month to evaluate the participant's health status, including any changes to treatment and assessment of anxiety and depressive symptoms. Another interim check-up is scheduled at 3 months to assess the patient's health status. The interview will also assess any changes to treatment, anxiety and depressive symptoms, quality of life, and psychomotor function. A final visit will be scheduled at 6 months for an assessment of the participant's health. The interview will also assess any changes to treatment, anxiety and depressive symptoms, quality of life, and psychomotor function.

Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder

Background: Most medications that treat depression take weeks or months to work. Researchers want to develop fast-acting treatments. One dose of ketamine has a rapid antidepressant effect. For most people, this lasts a week or less. Repeated doses of ketamine may help maintain this effect. Objective: Main Study: To study the effects of ketamine in treating depression. Ketamine Metabolites Substudy: To study how ketamine effects brain chemistry. To study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down. Eligibility: Main Study: People ages 18-65 with major depressive disorder and healthy volunteers Ketamine Metabolites Substudy: Healthy volunteers ages 18-65 Design: Main Study: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 phases totaling 14-20 weeks. Phase I (2-7 weeks): * Gradually stop current medications * MRI: Participants lie and perform tasks in a machine that takes pictures of the body. * Mood and thinking tests * Blood and urine tests * Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep. * Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity. * Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks. Phase I tests are repeated in Phases II and III and in the final visit. Phase II (4-5 weeks): * 4 weekly IV infusions of ketamine or a placebo during an MRI or MEG. For the MEG, a cone over the head records brain activity. Phase III (optional): * 8 infusions of ketamine over 4 weeks Phase IV (optional): * Symptoms monitoring for 4 weeks * Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months. Ketamine Metabolites Substudy: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 days. Study Procedures: Mood and thinking tests Blood and urine tests 1 infusion of ketamine Spinal tap and spinal catheter: Used to get samples of cerebrospinal fluid (CSF). This is a fluid that moves around and within the brain and spinal cord. Studying CSF will help us learn how ketamine effects brain chemistry ...

A Study of Vortioxetine in Japanese Pediatric Patients With Major Depressive Disorder

The main aim of the study is to check how well vortioxetine 10 mg/day or 20 mg/day works and to check for side effects compared to a placebo on depression symptoms in Japanese teenagers aged 12 to 17 years with a diagnosis of Major Depressive Disorder (MDD). The overall time each participant will be in the study is about 20 weeks. This includes up to 15 days (about 2 weeks) to check who can take part, a 14-week period where everyone receives vortioxetine or a placebo, and after that, a 4-week period to check for any side effects after treatment. During the study, participants will visit their clinic 13 times.

Psilocybin in Co-occuring Major Depressive Disorder and Borderline Personality Disorder

The primary objective of the study is to evaluate the safety and efficacy of psilocybin in adults with major depressive disorder (MDD) and borderline personality disorder (BPD).

Tracking Response to Antidepressants in Advance of Investigational Trials

TRAIT is an open-label observational study to evaluate treatment response to selective-serotonin reuptake inhibitors (SSRIs) and selective-norepinephrine reuptake inhibitors (SNRIs) among individuals meeting criteria for Major Depressive Disorder (MDD) and seeking enrollment in investigational trials.

"A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder"

The purpose of this study is to examine the efficacy, safety, and tolerability of CYB003 compared to matching placebo as adjunctive treatment in participants with MDD.

Digital Phenotypes for Predicting Depression_Validation

This 12-month, single-site prospective observational study will prospectively monitor the recurrence of mood episodes while continuously collecting passive digital phenotypes in individuals with and without mood disorders. A total of 200 adults will be enrolled, including 100 patients with major depressive disorder or bipolar I/II disorder and 100 healthy control participants. Participants will complete five clinical assessments at 3-month intervals and will continuously wear a consumer wearable device and use the My Mental HERO smartphone application for passive sensing and daily mood recording. Structured clinical interviews will identify the occurrence, subtype, and day-level onset and offset of mood episodes during follow-up. The study will examine longitudinal digital phenotypes associated with mood states and subsequent mood episode onset. It is designed to provide an independent validation dataset for digital phenotypes and prediction models developed in the preceding MentalHERO prospective observational cohort (ClinicalTrials.gov Identifier: NCT07151846). Because the two cohorts follow closely aligned study protocols and assessment schedules, data from both cohorts may also be pooled for secondary analyses where appropriate.

Psychopharmacotherapy for Depressive Patients

The primary purpose of this study is to compare the short (12 week) and long-term (1-year) efficacy and the tolerability between stepwise psychopharmacotherapy and antidepressant monotherapy for 12 weeks in adult patients with major depressive disorders, stratified by the multimodal serum biomarker scores.

Study of ALTO-300 in MDD

The purpose of this study is to determine efficacy differences between ALTO-300 and placebo, used adjunctively to an antidepressant, related to patient characteristics.

NMDA Modulation in Major Depressive Disorder

Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. Therefore, this study will examine the efficacy and safety as well as cognitive function improvement of an NMDA enhancer (NMDAE) in the treatment of MDD in the adults.