What additional weight‑loss medication should be added for a 28‑year‑old male with a colostomy, weighing 522 lb, who is already taking bupropion?

Additional Weight Loss Medication for a 28-Year-Old Male with Colostomy on Bupropion

Add naltrexone to the existing bupropion regimen to create the FDA-approved combination naltrexone/bupropion (Contrave), which produces superior weight loss compared to bupropion monotherapy and is specifically designed for severe obesity like this patient's.

Rationale for Naltrexone/Bupropion Combination

Since this patient is already taking bupropion, the most logical and evidence-based approach is to add naltrexone to create the synergistic FDA-approved combination therapy. The naltrexone/bupropion combination activates POMC neurons in the arcuate nucleus, causing release of alpha-melanocyte-stimulating hormone, which projects to hypothalamic areas controlling feeding and body weight 1.

Efficacy Data

• The combination produces 5.0-9.3% total body weight loss over 56 weeks, with placebo-subtracted weight loss of 3.2-5.2% 2
• 45-66% of patients achieve ≥5% weight loss, with placebo-subtracted proportion of 23-34% 2
• Real-world data demonstrates median weight loss of 8.8% at 12 months in treatment-naive patients 3
• The combination is significantly more effective than bupropion monotherapy, which produces only 2.77-2.8 kg weight loss at 6-12 months 1, 4

Dosing Protocol

Start with 1 tablet daily (8 mg naltrexone/90 mg bupropion) and increase by 1 tablet weekly to a maximum of 2 tablets twice daily (32 mg/360 mg total daily dose) 1. This gradual escalation minimizes adverse effects, particularly nausea 1.

Response Assessment

• Discontinue if <5% weight loss is not achieved after 12 weeks at maximum tolerated dose 1
• Monitor weight monthly during the first 3 months, then quarterly 5

Special Considerations for Colostomy

The colostomy does not contraindicate naltrexone/bupropion use. However, be aware that:

• Common gastrointestinal side effects include nausea (most common), constipation, and vomiting 2, 6
• 28.6% of patients experience constipation during dose escalation, and 39.8% report side effects at optimal dosage 6
• The constipation may be less problematic in a patient with a colostomy, but monitor stoma output and hydration status
• Slower dose titration can help manage gastrointestinal side effects 1

Alternative First-Line Options (If Combination Not Feasible)

If adding naltrexone to existing bupropion is not possible or the patient cannot tolerate the combination, consider these alternatives in order of efficacy:

GLP-1 Receptor Agonists (Preferred)

Semaglutide 2.4 mg weekly or tirzepatide represent superior first-line options with 15-21% weight loss, far exceeding naltrexone/bupropion efficacy 5. These agents:

• Produce the greatest weight loss of any pharmacotherapy 5
• Have proven cardiovascular benefits 5
• Work through appetite reduction, increased satiety, and delayed gastric emptying 1
• Require subcutaneous injection with weekly dosing 5

Phentermine/Topiramate ER

Phentermine/topiramate ER produces greater weight loss than naltrexone/bupropion and should be considered if GLP-1 agonists are unavailable 1:

• Start at 3.75/23 mg daily for 14 days, then increase to 7.5/46 mg daily 1
• Can escalate to 15/92 mg daily if needed 1
• Discontinue if <3% weight loss after 12 weeks at 7.5/46 mg or <5% weight loss after 12 weeks at 15/92 mg 1

Critical Safety Monitoring

Contraindications to Screen For

• Uncontrolled hypertension or cardiovascular disease (relevant for sympathomimetic agents if considering alternatives) 4
• Seizure disorders (bupropion lowers seizure threshold) 2
• Eating disorders or history of suicidal ideation (rare but serious adverse effects include suicidal thoughts) 2
• Monoamine oxidase inhibitor use within 14 days (contraindicated with bupropion) 4

Monitoring Requirements

• Blood pressure and heart rate monitoring - there is typically a small increase in heart rate with naltrexone/bupropion 2
• Mental health screening for mood changes or suicidal ideation 2
• Metabolic parameters: waist circumference, triglycerides, HDL-cholesterol, and insulin resistance typically improve 2

Discontinuation Rates and Adherence

Be aware that 52.7% of patients discontinue naltrexone/bupropion within 12 months, primarily due to side effects 6. However, real-world data shows 38.5% of patients continue treatment at 12 months with sustained weight loss 3. Setting realistic expectations about side effects during the dose escalation phase improves adherence 6.

Adjunctive Considerations

• Ensure comprehensive lifestyle intervention is concurrent, including reduced-calorie diet and increased physical activity, as pharmacotherapy is only effective as an adjunct 1, 4
• Review and minimize medications that promote weight gain, such as certain antipsychotics, tricyclic antidepressants, and beta-blockers 4, 5
• Consider bariatric surgery referral if BMI ≥40 kg/m² (which this patient likely meets at 522 lbs) or BMI ≥35 kg/m² with comorbidities and pharmacotherapy fails 4