Overview

Dopamine D3 Receptor Occupancy in Bipolar Depression

Status:
Not yet recruiting
Trial end date:
2023-06-01
Target enrollment:
0
Participant gender:
All
Summary
Bipolar disorder is a common condition that can cause significant disability and risk for suicide. Second generation antipsychotic medications can be used to treat depression in bipolar disorder, yet we do not know how they work. Here, we will use a recently approved medication, cariprazine (Vraylar), to treat participants with bipolar depression. They will have brain imaging with PET scans before and during treatment to understand how the medication may be working. Particularly, we will look at the role of the D3 dopamine receptor.
Phase:
Phase 4
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
New York State Psychiatric Institute
Treatments:
Cariprazine
Criteria
Inclusion Criteria:

1. Capacity to provide consent, and informed consent provided

2. Diagnosis of bipolar I disorder and currently meet criteria for DSM5 major depressive
episode

3. Depression at enrollment of sufficient severity to score at least 16 on the first 17
items of the Hamilton Depression Rating Scale when including the atypical depression
items addendum

4. Age 18-60 years old

5. Patients who are on antidepressant (SSRI, SNRI or bupropion) or antipsychotic
medications at presentation will be included if they have failed that regimen, as
defined as not achieving at least partial remission after an adequate dose of
medications for at least four weeks. Fluoxetine will not be allowed due to its long
half-life. Patients will be able to continue to take other mood stabilizer medications
(lamotrigine, lithium, valproate, carbamazepine or oxcarbazepine) if they had not made
changes to the dose of those medications within eight weeks of signing consent.
Benzodiazepines and hypnotics are allowed throughout the study. If taking stimulant
medications, they must be willing not to take these during the study.

6. Females of child-bearing potential must be willing to use an acceptable method of
birth control throughout the study; abstinence if it does not require changes to usual
behavior, birth control pill, male condom, IUD, dep- provera, norplant, male
sterilization or female sterilization are acceptable.

7. Participant is likely to tolerate medication washout if indicated

Exclusion Criteria:

1. Diagnosis of any other major psychiatric disorders such as schizoaffective disorder,
current psychotic depression. Any recent drug or alcohol use disorder; within 3 months
before the study unless mild. Participant meets DSM5 criteria for manic episode at the
time of screening, or has YMRS > 12.

2. Previous failed trial of cariprazine, defined by at least six weeks of treatment at
the dose of 1.5 mg per day or more. Experienced intolerable side effects of
cariprazine in the past. Taking any medications that are either contraindicated or
that have clinically significant drug-drug interactions (such as strong CYP3A4
inducers) with cariprazine, unless there is a plan to stop these as part of the
washout.

3. History of clinical deterioration when any of the medications that the participant is
taking at presentation have been discontinued in the past if they will be discontinued
as part of the washout.

4. First-degree family history of schizophrenia if the participant is less than 33 years
old.

5. Significant active physical illness, including blood dyscrasias, lymphomas,
hypersplenism, endocrinopathies, renal failure, chronic obstructive lung disease,
autonomic neuropathies, peripheral vascular disease, neuromuscular disorder or tardive
dyskinesia. Any medical diagnoses that would be a contraindication to cariprazine
treatment, including any movement disorders. Any history of a seizure disorder.

6. Actively suicidal, as defined by expressive ideation with a plan and intent for
suicide, or developing suicidal ideation that requires immediate medical or treatment
intervention.

7. Active lactation

8. Electroconvulsive therapy within the past 6 months

9. Participants who endorse a history of prior head trauma and score 1.5 standard
deviations below the mean of Trailmaking A & B test

10. Metal implants, cardiac pacemaker, metal prostheses, metal orthodontic appliances or
shrapnel in the body unless there is confirmation that the substance is MRI compatible

11. Current, past or anticipated exposure to radiation, including:

A. Having been badged for radiation exposure in the workplace B. Participation in
nuclear medicine protocols in the past year. However, participants will be eligible if
the injected dose and dosimetry of the radiotracer used are known and the cumulative
annual exposure of the previous study and this study is lower than the annual limit
for research participants defined by FDA (21 CFR 361.1)

12. History of claustrophobia that would prevent participation in imaging scans.

13. Inadequate understanding of English

14. Weight >350 lbs or inability to fit into the MRI scanner