Is it safe to prescribe Contrave (bupropion and naltrexone) to a patient with a history of methamphetamine use?

Prescribing Contrave to Patients with History of Methamphetamine Use

Contrave (naltrexone/bupropion) should not be prescribed to patients with a history of methamphetamine use due to safety concerns and potential for adverse effects. While Contrave is approved for weight management, its components have specific interactions with stimulant use disorders that warrant caution.

Components of Contrave and Their Relevance

• Contrave is a combination medication containing naltrexone (opioid antagonist) and bupropion (aminoketone antidepressant) approved for chronic weight management 1
• Bupropion component has been studied for methamphetamine use disorder with concerning results:
  • A pilot study in adolescents with methamphetamine abuse/dependence showed bupropion was associated with worse outcomes compared to placebo 2
  • Females receiving bupropion provided significantly fewer methamphetamine-free urine tests compared to those receiving placebo 2

Safety Concerns

• Bupropion carries a risk of seizures, which is particularly concerning in patients with stimulant use history 1
• Contrave is contraindicated in patients with seizure disorders, which may be more prevalent in those with history of methamphetamine use 1
• One study participant receiving bupropion was hospitalized for suicidal ideation during methamphetamine relapse, highlighting potential psychiatric risks 2

Current Evidence on Bupropion/Naltrexone for Methamphetamine Use

• While a 2021 study showed some benefit of naltrexone-bupropion combination for active methamphetamine use disorder, the response rate was still quite low (13.6% vs 2.5% for placebo) 3
• This study used injectable naltrexone rather than the oral formulation found in Contrave 3
• Medication adherence is a significant concern - one study showed only 32% adherence to bupropion among methamphetamine users 4

Alternative Approaches

• For patients with methamphetamine use history requiring weight management:
  • Consider other FDA-approved weight loss medications without CNS stimulant properties, such as orlistat or liraglutide 1
  • For patients with acute methamphetamine intoxication, benzodiazepines are the recommended treatment of choice 1

Clinical Decision Algorithm

1. Assess for current methamphetamine use:

   • If active use or recent use with signs of intoxication: Absolutely avoid Contrave 1
   • If history of use but prolonged abstinence: Still avoid Contrave due to risk of relapse and adverse interactions 2

2. Evaluate for seizure history or risk factors:

   • Any history of seizures is an absolute contraindication to Contrave 1
   • Methamphetamine use increases seizure risk, creating a compounded risk 1

3. Consider psychiatric comorbidities:

   • Depression with suicidal ideation is a contraindication for bupropion-containing products 1
   • History of methamphetamine use increases risk of psychiatric complications 2

Important Caveats

• Weight management in patients with substance use disorders requires specialized care beyond medication alone 1
• The risk-benefit ratio for Contrave in this population strongly favors avoiding this medication 2, 3
• Current research is exploring alternative formulations of naltrexone-bupropion for methamphetamine use disorder, but these are investigational and differ from the commercially available Contrave 5