Clinical Trials

Inclusion Criteria:

* Men or women between 18 to 65 years old.
* Patients with a SCID IV confirmed diagnosis of bipolar disorder (BDI or BDII) or schizoaffective bipolar type (SZA-BD).
* Women with a negative pregnancy test 48 hours before study entry (obesity phenotyping visit).
* Patients with a negative urine drug screen except for allowable drugs.
* Patients with a BMI ≥ 30 kg/m2 or a BMI ≥ 27 kg/m2 plus one medical comorbidity (e.g., type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea)
* Patients must be undergoing mood stabilizer treatment but may also receive concurrent antidepressant or anxiolytic therapy.
* Patients must be on a stable regimen of a mood stabilizer, with no changes to the medication, for at least one month prior to study enrollment.
* Continuation of mood-stabilizing treatment is preferred but not required; the decision should be made in collaboration with the participant's primary mental health provider.

Exclusion Criteria:

* Abdominal bariatric surgery: Gastric bypass surgery (Roux-en-Y), Adjustable gastric band (Lap band), and Gastric sleeve surgery (Sleeve gastrectomy).
* Positive history of chronic gastrointestinal diseases, or systemic disease that could affect gastrointestinal motility, such as diabetic gastroparesis; or use of medications that may alter gastrointestinal motility and appetite.
* Positive history of chronic gastrointestinal diseases that could affect gastrointestinal absorption such as inflammatory bowel disease (IBD), celiac disease, small intestinal bacterial overgrowth (SIBO), etc; or use of medications that may alter gastrointestinal absorption.
* Significant untreated psychiatric dysfunction.
* Hypersensitivity to any of the study medications.
* Contraindications to the FDA-approved medications: Phentermine-Topiramate Extended Release; Oral naltrexone extended-release/bupropion extended-release (NBSR; Contrave®, Mysimba™); and Semaglutide (Weygovy™).
* Inability to provide informed consent: participants who are on involuntary commitment, conservatorship or under a legal guardian.
* Patients with active hypomania or mania (YMRS ≥ 12 points)
* Patients with active severe depression (MADRS ≥ 30 points)
* Patients with active psychosis (YMRS item 8 ≥ 6 points)
* Patients with active suicide ideation (MADRS item 10 ≥ 4 points)
* Patients with any medication changes (mood stabilizers) without advisement of study clinicians or clinical provider.
* Patients with active bulimia (purging)
* Current drug and/or alcohol use disorders (except nicotine)
* Patients with a positive toxicology screening (except cannabis)
* Positive toxicology screen for cannabis and a cannabis use disorder by CUDIT-R.
* Participants who use cannabis for recreational or medicinal purposes and fail the toxicology screen can potentially be included in the study only if they take the CUDIT-R and score a 12 or less.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/10/2025. Questions regarding updates should be directed to the study team contact.