Individualized Pharmacological Approach to Obesity in Patients With Bipolar Disorder

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 ≥ 20 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) or anorexia (severe restriction) * Patients with a history of bulimia (purging behaviors) or anorexia (severe dietary restriction) within the 12 months preceding study enrollment will be excluded * 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. * Patients unwilling to complete the full phenotyping day on its current form (i.e. patients avoiding gluten meal or adhering to a vegan diet).