Weight Loss Medications for Obesity in Bipolar Disorder

(OBOE-Mayo Trial)

Overseen By Karin M Lindstrom, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must be taking: Mood stabilizers

Must not be taking: Gastrointestinal motility drugs

Disqualifiers: Bariatric surgery, Untreated psychiatric dysfunction, Active psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different weight loss medications work for people with obesity who also have bipolar disorder. Researchers aim to determine which medication might be best based on specific eating habits, such as frequent hunger or emotional eating. Participants will receive one of three medications—Naltrexone/Bupropion, Phentermine/Topiramate, or Semaglutide (a weight loss drug)—or join a group therapy program for weight management. Individuals diagnosed with bipolar disorder and struggling with obesity might be a good fit for this study. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, allowing researchers to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a stable mood stabilizer regimen for at least one month before joining the study, and any changes to mood stabilizers should be advised by study clinicians or your clinical provider.

What is the safety track record for these treatments?

Previous studies have shown that semaglutide offers promising safety results for weight management. Research indicates it does not increase the risk of depression or suicidal thoughts, though some reports have raised concerns about eating disorders.

For naltrexone/bupropion, studies have demonstrated its effectiveness in weight loss but note a potential increase in blood pressure. Participants should monitor their blood pressure while taking this medication.

Phentermine/topiramate has proven effective for weight loss, but caution is advised due to possible psychological side effects. One study reported a case of mania in a person with bipolar disorder who took phentermine.

These medications have FDA approval for weight loss, suggesting safety for this purpose. However, participants should be aware of possible side effects and discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for obesity in bipolar disorder because they target different mechanisms tied to how our bodies and minds experience hunger. Unlike typical weight loss drugs, Semaglutide (Wegovy) works by mimicking a hormone called GLP-1 to regulate appetite and is paired with group therapy to tackle the "Hungry Gut" type of hunger. Naltrexone/Bupropion (Contrave) is unique because it combines two drugs to address the psychological cravings, known as "Emotional Hunger." Phentermine/Topiramate (Qysmia) is distinctive for targeting the "Hungry Brain" by increasing feelings of fullness and reducing appetite. These treatments are being explored not just for their weight-loss potential but also for how they might uniquely benefit individuals with bipolar disorder.

What evidence suggests that this trial's treatments could be effective for weight loss in patients with bipolar disorder?

Research has shown that Semaglutide, which participants in this trial may receive, can help people lose about 10% to 15% of their weight over several weeks. It is considered safe and effective for weight loss, even for those with stable bipolar disorder.

For Naltrexone/Bupropion, another treatment option in this trial, studies indicate it can lead to significant weight loss, especially when combined with lifestyle changes. About 65% of people using it lost at least 5% of their body weight.

Phentermine/Topiramate, also studied in this trial, has helped people lose an average of 9% to 11% of their weight over a year. It effectively aids many in losing a noticeable amount of weight.

All three medications are tested in this trial, offering different benefits based on individual needs. ^{6 7 8 9 10}

Who Is on the Research Team?

Mark A Frye, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with bipolar disorder who are also dealing with obesity. Participants should be interested in weight loss and willing to undergo various assessments, including interviews, questionnaires, ECGs, and drug tests. They must commit to a nearly 18-week study period involving both in-person visits and virtual group therapy sessions.

Inclusion Criteria

I am between 18 and 65 years old.

I have been diagnosed with bipolar disorder or schizoaffective bipolar type.

I have taken a pregnancy test within 48 hours before the study, and it was negative.

Exclusion Criteria

Patients with active suicide ideation (MADRS item 10 ≥ 4 points)

Patients with active bulimia (purging)

Current drug and/or alcohol use disorders (except nicotine)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Initial assessments including informed consent, diagnostic interview, vital signs, mood questionnaires, ECG, and urine tests

1 week

1 visit (in-person)

Phenotyping and Drug Assignment

Comprehensive obesity phenotyping and assignment to study medication or behavioral intervention

1 week

1 visit (in-person)

Treatment

Participants receive assigned treatment and engage in a 12-week virtual group therapy program

12 weeks

4 visits (in-person), 4 phone calls, 12 virtual group sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone/Bupropion
• Phentermine/Topiramate
• Semaglutide

Trial Overview The trial aims to find the best medication for weight loss based on individual characteristics of people with bipolar disorder. It involves comparing three FDA-approved medications: Semaglutide (Wegovy®), Naltrexone/Bupropion (Contrave®), or Phentermine/Topiramate (Qysmia®). Some participants may not receive any medication but will still participate in a virtual group therapy program.

How Is the Trial Designed?

Group I: Semaglutide (Wegovy) + Group Therapy Program Experimental Treatment 2 Interventions

By meeting the satiety/return to hunger (Hungry Gut) phenotype, participants will take Semaglutide (Wegovy) and attend a 12-week group therapy session for the 16-week clinical trial.

Group II: Phentermine/Topiramate (Qysmia) + Group Therapy Program Experimental Treatment 2 Interventions

By meeting the satiation (Hungry Brain) phenotype, participants will take Phentermine/Topiramate (Qysmia) and attend a 12-week group therapy session for the 16-week clinical trial.

Group III: No Study Medication + Group Therapy Program Experimental Treatment 1 Intervention

By meeting the slow burn phenotype, participants will attend a 12-week group therapy session for the 16-week clinical trial.

Group IV: Naltrexone/Bupropion (Contrave) + Group Therapy Program Experimental Treatment 2 Interventions

By meeting the behavioral/psychological (Emotional Hunger) phenotype, participants will take Naltrexone/Bupropion (Contrave) and attend a 12-week group therapy session for the 16-week clinical trial.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9722598/

Naltrexone plus Bupropion Combination Medication and ... Trials found naltrexone/bupropion effective for obesity (25,26) leading to FDA-approval (22) and one trial found it significantly enhanced BWL ...

2. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.20220267

Naltrexone-Bupropion and Behavior Therapy, Alone ... In terms of weight loss, however, naltrexone-bupropion did not differ significantly from placebo, and the observed 2.1% weight loss was lower ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07213466

Study Details | NCT07213466 | Individualized ... This is a single-site, open-label, non-randomized interventional pilot study evaluating a phenotype-guided pharmacological approach to obesity ...

4. karger.com karger.com/ofa/article/18/5/481/925952/The-Effectivity-and-Safety-of-Naltrexone-Bupropion

The Effectivity and Safety of Naltrexone/Bupropion in ... Conclusion: NB treatment combined with lifestyle intervention results in significant weight loss after 6 and 12 months. Despite high ...

5. contravehcp.com contravehcp.com/efficacy/early-responder-efficacy/

Early responder efficacy | CONTRAVE® (naltrexone HCl ... Sixty-five percent of patients receiving CONTRAVE achieved ≥5% weight loss vs 22% of patients receiving placebo. ITT data analysis included all randomized ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/200063s020lbl.pdf

Contrave - accessdata.fda.gov Safety margins were estimated using body surface area exposure (mg/m2) based on a body weight of 100 kg. Daily oral administration of naltrexone has been shown ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/naltrexone-and-bupropion-oral-route/description/drg-20122495

Naltrexone and bupropion (oral route) - Side effects & ... Naltrexone and bupropion combination is used together with a reduced-calorie diet and proper exercise to help lose weight.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11743856/

Safety and effects of anti-obesity medications on weight loss ... Naltrexone/bupropion carries a risk of increased blood pressure. Phentermine/topiramate should be used with caution due to its higher risk of ...

9. medsafe.govt.nz medsafe.govt.nz/profs/PUArticles/June2025/Spotlight-on-Contrave.html

Spotlight on Contrave (naltrexone + bupropion) Contrave contains naltrexone and bupropion and is indicated for weight management in adults. Significant safety issues associated with Contrave ...

10. contravehcp.com contravehcp.com/safety/

Safety | CONTRAVE® (naltrexone HCl/bupropion HCl) Understand the safety and tolerability profile of CONTRAVE® (naltrexone HCl/bupropion HCl) as demonstrated across multiple phase 3 trials.