Can Naltrexone Be Prescribed with Phentermine, Lorazepam, and Ambien?
Yes, naltrexone can be prescribed with phentermine, lorazepam (Ativan), and zolpidem (Ambien), but only if the patient is on a stable benzodiazepine regimen without plans for abrupt discontinuation, and with careful cardiovascular and seizure risk monitoring. The critical contraindication is abrupt benzodiazepine discontinuation, not concurrent stable use.
Critical Safety Considerations
Absolute Contraindications to Address First
The most important safety concern is the risk of abrupt benzodiazepine discontinuation. Naltrexone-bupropion ER is absolutely contraindicated if there are any plans to abruptly stop lorazepam, as this dramatically increases seizure risk 1. The patient must remain on a stable lorazepam dose throughout naltrexone-bupropion treatment 1.
Additional absolute contraindications that must be ruled out include:
- Current opioid use (naltrexone blocks opioid receptors) 2, 1
- Seizure disorders or conditions predisposing to seizures 3, 2, 1
- Uncontrolled hypertension 2, 1
- Pregnancy or plans to become pregnant 2
- Use of MAOIs within the past 14 days 2
Drug Interaction Analysis
Phentermine + Naltrexone-Bupropion Combination: This combination is feasible but requires heightened cardiovascular monitoring. Both phentermine and the bupropion component can elevate blood pressure and heart rate 3, 2. A pilot study demonstrated that adding phentermine to weight loss medications yielded double the weight loss compared to monotherapy, suggesting potential synergistic benefits 4. However, phentermine should be avoided in patients with established cardiovascular disease 3.
Lorazepam (Ativan) + Naltrexone-Bupropion: Stable benzodiazepine use is not an absolute contraindication, but abrupt discontinuation is 1. The patient must be counseled that any changes to lorazepam dosing must be gradual and supervised. The bupropion component lowers seizure threshold, and combining this with benzodiazepine withdrawal creates compounded seizure risk 1.
Zolpidem (Ambien) + Naltrexone-Bupropion: This combination requires timing adjustments. Naltrexone-bupropion should be taken early in the day due to its potential to cause insomnia 3, 2. The patient may experience competing effects—bupropion's activating properties versus zolpidem's sedative effects. Consider whether the patient's insomnia might improve with weight loss and potentially allow zolpidem discontinuation over time.
Mandatory Monitoring Protocol
Cardiovascular Monitoring
- Baseline: Blood pressure and heart rate measurement before initiating therapy 2, 1
- First 12 weeks: Periodic blood pressure and heart rate monitoring, especially critical given the combination with phentermine 2, 1
- Ongoing: Continue periodic cardiovascular monitoring throughout treatment 2
Hepatic Monitoring
- Liver function tests every 3-6 months during long-term naltrexone treatment 2, 1
- More frequent monitoring (every 2-4 weeks) if naltrexone doses exceed 50 mg/day 2
- Patients with chronic hepatitis C or HIV require essential surveillance 2
Neuropsychiatric Monitoring
- Close monitoring for mood changes, suicidal ideation, and behavioral changes, particularly in the first months of treatment 2
- Bupropion carries a black box warning for increased suicidal thoughts in young adults under 24 years 2
- Assess for agitation, restlessness, and worsening anxiety 2
Seizure Risk Assessment
- Evaluate all factors that lower seizure threshold before initiating therapy 1
- Ensure patient understands the absolute necessity of maintaining stable benzodiazepine dosing 1
- Document that patient has no history of seizure disorders 2, 1
Dosing Strategy
Naltrexone-Bupropion Titration Schedule
The gradual titration minimizes gastrointestinal adverse effects and allows assessment of tolerability 2:
- Week 1: Naltrexone 8 mg/bupropion 90 mg once daily in the morning 2
- Week 2: Naltrexone 8 mg/bupropion 90 mg twice daily 2
- Week 3: Naltrexone 16 mg/bupropion 180 mg in morning, 8 mg/90 mg in evening 2
- Week 4 and beyond: Target dose of naltrexone 16 mg/bupropion 180 mg twice daily (total daily: naltrexone 32 mg/bupropion 360 mg) 2
Timing Considerations
- Administer naltrexone-bupropion early in the day to minimize insomnia risk 3, 2
- Phentermine should also be taken early in the day 3
- Zolpidem should be taken at bedtime as prescribed
- Lorazepam timing should remain unchanged from current regimen
Clinical Advantages of This Combination
This patient may be an ideal candidate for naltrexone-bupropion given the concurrent anxiety and insomnia, which suggest possible comorbid depression 2. The bupropion component may address underlying mood symptoms while promoting weight loss 2. Patients with anxiety disorders often have difficulty with weight management, and addressing both conditions simultaneously may improve overall outcomes 2.
The combination of phentermine with naltrexone-bupropion may provide enhanced weight loss compared to either agent alone, though this requires careful cardiovascular monitoring 4.
Common Pitfalls to Avoid
Do not initiate naltrexone-bupropion if there are any plans to taper or discontinue lorazepam without first completing the benzodiazepine taper 1
Do not overlook cardiovascular screening given the triple combination of sympathomimetic agents (phentermine and bupropion) 3, 2
Do not prescribe if the patient has undiagnosed or untreated hypertension 2, 1
Do not assume the patient is opioid-free—explicitly confirm no current opioid use, including tramadol and codeine-containing products 2, 1
Do not fail to counsel on contraception if the patient is a woman of childbearing potential, as naltrexone-bupropion is contraindicated in pregnancy 2
Expected Outcomes
With appropriate monitoring and stable concurrent medications, patients can expect: