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Transforming the understanding
and treatment of mental illnesses.

Bipolar Disorder

Bipolar disorder, formerly called manic-depressive illness, is a mood disorder that causes unusual shifts in a person’s mood, energy, activity levels, concentration, and ability to carry out day-to-day tasks. The mood shifts in bipolar disorder are different from normal ups and downs — they include periods of extremely “up,” elated, irritable, or energized behavior (known as manic episodes) and very “down,” sad, indifferent, or hopeless periods (known as depressive episodes). Learn more about bipolar disorder.

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For opportunities to participate in NIMH research on the NIH campus, visit the clinical research website. Travel and lodging assistance may be available.

Featured Studies

Featured studies include only those currently recruiting participants. Studies with the most recent start date appear first.

NIMH Rhythms and Blues Study: A Prospective Natural History Study of Motor Activity, Mood States, and Bipolar Disorder

Study Type: Observational
Start Date: February 6, 2023
Eligibility: 12 Years to 70 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States


Mood disorders, such as bipolar disorder, can have serious effects on a person s life. People with bipolar disorder are more likely to have heart disease and abuse substances. In this natural history study, researchers would like to learn more about the connection between exercise and mental health in people with and without mood disorders.


To better understand relationships among physical activity, sleep, and mental health.


People aged 12 to 60 years with a history of a mood disorder. Healthy spouses and relatives with no mood disorders are also needed.


Participants will be in the study up to 2 years.

For up to 20 days in a row, at 4 times during the study, participants will:

Complete an electronic diary on their smartphone. Participants will answer questions about their mood, health, sleep, and daily activities.

Wear an activity monitor, like a wristwatch, that records how much they move.

Wear a light sensor, as a necklace, to record the amount of light in their environment.

Some participants will do additional tests. Twice during the study, for 3 days in a row, they will:

Wear monitors to record their temperature, heart rate, and sleep.

Provide saliva samples.

Complete cognitive tasks on their smartphone.

Participants will visit the NIH clinic 2 times. They will have a physical exam, with blood and urine tests. They will wear a heart monitor. They will ride a stationary bike for 30 minutes. They may have an imaging scan.

Some participants will stay overnight. They will go to sleep wearing a cap to measure their brain activity.

Transcranial Electric Stimulation Therapy (TEST) for Treatment Resistant Depression (TRD

Study Type: Interventional
Start Date: November 8, 2022
Eligibility: 25 Years to 64 Years, Does Not Accept Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States


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.


To study the safety and feasibility of TEST and assess its antidepressant effects.


Adults aged 25-64 with major depression that has not been relieved by current treatments.


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.

Academic-Community EPINET (AC-EPINET)

Study Type: Interventional
Start Date: March 16, 2022
Eligibility: 16 Years to 35 Years, Does Not Accept Healthy Volunteers
Location(s): Prevention and Recovery Center for Early Psychosis, Indianapolis, Indiana, United States; Strong Ties Young Adults Program- University of Rochester Medical Center, Rochester, New York, United States; Program for Risk Evaluation and Prevention (PREP) - University of Michigan, Ann Arbor, Michigan, United States; Early Psychosis Intervention Clinic-New Orleans (EPIC-NOLA) - Tulane University, New Orleans, Louisiana, United States; Recovery from Early Psychosis Program (REPP) - Northwestern University, Chicago, Illinois, United States; Vanderbilt's Early Psychosis Program - Vanderbilt University, Nashville, Tennessee, United States

The investigators propose to examine the effects of CSC services delivered via TH (CSC-TH) versus the standard clinic-based CSC model (CSC-SD) on engagement and outcomes in a 12-month, randomized trial.

Effectiveness RCT of Customized Adherence Enhancement

Study Type: Interventional
Start Date: February 1, 2022
Eligibility: 18 Years to 89 Years, Does Not Accept Healthy Volunteers
Location(s): MetroHealth Medical Center, Cleveland, Ohio, United States; The Nord Center, Lorain, Ohio, United States

Approximately one in two individuals with bipolar disorder (BD) are non-adherent with medication, often leading to severe and negative consequences. Unfortunately, there is no widely used evidence-based approach to target poor adherence among individuals with BD. Building upon positive efficacy trial results, the proposed project will test the effectiveness of technology-facilitated Customized Adherence Enhancement (CAE) vs. enhanced treatment as usual (eTAU) using a prospective randomized controlled design in public mental health care settings and preferentially enrolling poorly adherent/high-risk individuals with BD. Deliverables include a curriculum-driven adherence enhancement approach that can be implemented in public healthcare settings and which can improve outcomes for the most vulnerable groups of people with BD.

Effects of Theta Burst Stimulation on the Brain, Behavior, and Clinical Symptoms in Adults With Bipolar Disorder

Study Type: Interventional
Start Date: April 6, 2021
Eligibility: 18 Years to 35 Years, Accepts Healthy Volunteers
Location(s): University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Bipolar Disorder (BD) is a common and highly debilitating psychiatric disorder, however, the predisposing brain mechanisms are poorly understood. Here, the investigators aim to examine the immediate effect of transcranial brain stimulation (TBS) on brain activity and emotions in adults with and without BD as a first stage toward understanding the predisposing brain mechanisms of BD. The investigators hypothesize that TBS will reduce brain activity while playing a game with rewards in all adults, but the TBS will reduce brain activity more in the adults with BD compared to adults without BD. Furthermore, the investigators hypothesize that this reduced brain activity will be associated with reduced BD symptoms, such as negative emotions.

IM Ketamine vs Midazolam for Suicidal ER Patients

Study Type: Interventional
Start Date: January 2, 2021
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): Comprehensive Psychiatric Emergency Department of Columbia University Medical Center, New York, New York, United States

Rising US suicide rates and the increased risk of suicide among persons who visit an emergency department (ED) for suicidality make the ED an important site for interventions to prevent suicide. There is no approved treatment for rapid relief of suicidal thoughts although clinical trials, including ours, show relief of suicidal thoughts within hours of treatment with inexpensive, generic, sub-anesthetic ketamine. We propose a clinical trial of intramuscular ketamine in depressed ED patients with high-risk suicidality, which if successful would support a novel, easy-to-use, scalable intervention for busy emergency clinicians to implement.

In-person vs. Remote Wellness Support

Study Type: Interventional
Start Date: November 24, 2020
Eligibility: 18 Years to 65 Years, Does Not Accept Healthy Volunteers
Location(s): University of Texas Health Science Center - Department of Psychiatry, San Antonio, Texas, United States

The study team will use components of the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to compare Cognitive Adaptation Training (CAT) to Remotely delivered Cognitive Adaptation Training (R-CAT) 1-9 within a managed care organization (MCO), targeting members with serious mental illness (SMI) needing assistance with the regular taking of medication.

Intervention for Comorbid Substance Use and Bipolar Disorders

Study Type: Interventional
Start Date: October 1, 2020
Eligibility: 18 Years and Older, Does Not Accept Healthy Volunteers
Location(s): Butler Hospital, Providence, Rhode Island, United States

This trial aims to evaluate the effectiveness of a novel intervention for patients with co-occurring bipolar and substance use disorders following a psychiatric hospitalization. Half of the participants will receive a specialized psychosocial intervention program, while the other half will receive an enhanced safety monitoring program, both provided in addition to their routine care.

Unobtrusive Monitoring of Affective Symptoms and Cognition Using Keyboard Dynamics (UnMASCK)

Study Type: Observational
Start Date: September 17, 2020
Eligibility: 25 Years to 50 Years, Accepts Healthy Volunteers
Location(s): University of Illinois at Chicago, Chicago, Illinois, United States

Mood disorders are associated with significant financial and health costs for the United States, partially due to cognitive problems in these patients that can worsen disease course and impair treatment response. This study proposes to use smartphone-based technology to monitor cognitive problems in patients with mood disorders by linking brain network changes with predicted worsening of mood symptoms. The proposed study will provide evidence for using smartphone-based passive sensing as a cost-effective way to predict illness course and treatment response.

Multi-modal Assessment of Gamma-aminobutyric Acid (GABA) Function in Psychosis

Study Type: Interventional
Start Date: January 16, 2020
Eligibility: 16 Years to 60 Years, Accepts Healthy Volunteers
Location(s): University of Michigan, Ann Arbor, Michigan, United States

The purpose of this study is to better understand mental illness and will test the hypotheses that while viewing affective stimuli, patient groups will show increased blood oxygenation level dependent (BOLD) signal by fMRI after lorazepam.

This study will enroll participants between the ages of 16 and 60, who have a psychotic illness (such as psychosis which includes conditions like schizophrenia, schizoaffective disorder, and mood disorders). The study will also enroll eligible participants without any psychiatric illness, to compare their brains.

The study will require participants to have 3-4 sessions over a few weeks. The initial assessments (may be over two visits) will include a diagnostic interview and several questionnaires (qols) to assess eligibility. Subsequently, there will will be two separate functional magnetic resonance imaging (fMRI) sessions in which lorazepam or placebo will be given prior to the MRI. During the fMRI the participants will also be asked to answer questions. Additionally, the participants will have their blood drawn, women of child bearing potential will have a urine pregnancy test, vital signs taken, and asked to complete more qols.

Evaluation of Patients With Mood and Anxiety Disorders and Healthy Volunteers

Study Type: Observational
Start Date: February 2, 2001
Eligibility: 3 Years to 99 Years, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

The purpose of this protocol is to allow for the careful screening of patients and healthy volunteers for participation in research protocols in the Experimental Therapeutics and Pathophysiology Lab (ETPB) at the National Institute of Mental Health (NIMH) and for the collection of natural history data. In addition the protocol will allow clinicians to gain more experience in the use of a variety of polysomnographic and high-density EEG recordings. Subjects in this protocol will undergo an evaluation which may include: a psychiatric interview; a diagnostic interview; rating scales; a medical history; a physical exam; brain magnetic resonance imaging (MRI); electroencephalography (EEG); electrocardiography (EKG), magnetoencephalography (MEG); blood, saliva and urine laboratory evaluation; and a request for medical records. Subjects may also be asked to complete questionnaires about attitudes towards research and motivation for research participation. The data collected may also be linked with data from other mood and anxiety disorder protocols (e.g., brain imaging, DNA, psychophysiology tests, treatment studies, etc) for the purposes of better understanding the diagnosis, pathophysiology, and treatment response of patients with mood disorders. Parents of minors will be interviewed. Upon conclusion of the screening process, subjects will either be offered participation in a research protocol and will sign the appropriate informed consent, or will be considered not appropriate for participation in research and will be referred back into the community. The current protocol thus serves as an entry point for individuals with mood or anxiety disorders or healthy volunteers to enter NIMH IRB approved ETPB protocols.

Evaluation of the Genetics of Bipolar Disorder

Study Type: Observational
Start Date: August 11, 1994
Eligibility: 18 Years and Older, Accepts Healthy Volunteers
Location(s): National Institutes of Health Clinical Center, Bethesda, Maryland, United States

This study looks to identify genes that may affect a person's chances of developing bipolar disorder (BP) and related conditions.