What are the weight loss medication options for individuals with a history of methamphetamine use who do not qualify for Glucagon-Like Peptide-1 (GLP-1) receptor agonists?

Weight Loss Medication Options for Individuals with History of Methamphetamine Use Who Don't Qualify for GLP-1 Agonists

For individuals with a history of methamphetamine use who do not qualify for GLP-1 receptor agonists, orlistat and naltrexone/bupropion are the most appropriate weight loss medication options, with orlistat being the safest first choice due to its non-stimulant, non-addictive properties and peripheral mechanism of action. 1

Understanding Contraindications for Stimulant-Based Medications

• Patients with a history of drug abuse, including methamphetamine use, should avoid stimulant-based weight loss medications such as phentermine and phentermine/topiramate ER 1
• These medications can trigger addictive behaviors or relapse in individuals with substance use history due to their sympathomimetic properties 1
• Stimulant-based medications are specifically listed as "poor candidates" for patients with history of drug abuse in clinical guidelines 1

First-Line Option: Orlistat

• Mechanism of action: Lipase inhibitor that blocks fat absorption in the intestine (works peripherally rather than centrally) 1

• Dosing: 120 mg three times daily with meals 1

• Expected weight loss: 3.1% at 1 year compared to placebo 1

• Advantages for patients with substance use history:

  • Non-addictive mechanism with no central nervous system effects 1
  • No known drug interactions with substances of abuse 1
  • Not a controlled substance 1
  • Approved for long-term use 1

• Common side effects: Oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, increased defecation, fecal incontinence 1

• Best candidates: Patients with hypercholesterolemia and/or constipation who can limit their intake of dietary fat 1

Second-Line Option: Naltrexone/Bupropion ER (Contrave)

• Mechanism of action: Opioid receptor antagonist/dopamine and norepinephrine reuptake inhibitor 1

• Dosing: Initial dose 8/90 mg daily (morning), with gradual dose escalation to 16/180 mg twice daily 1

• Expected weight loss: 4.8% at 56 weeks compared to placebo 1

• Unique considerations for substance use history:

  • Naltrexone component may help reduce cravings and addictive behaviors related to food 1
  • May provide dual benefit for patients trying to maintain abstinence from substances 1
  • Not a controlled substance 1

• Cautions:

  • Bupropion can cause insomnia, anxiety, and agitation which may be problematic for recovering stimulant users 2
  • Contraindicated with recent MAOI use 1
  • Monitor for mood changes as bupropion carries a black box warning related to potential increase in suicidal thoughts 1
  • Avoid in patients with history of seizures or conditions predisposing to seizure 1

• Common side effects: Nausea, constipation, headache, dizziness, insomnia, dry mouth 2

Medications to Avoid in This Population

• Phentermine: Adrenergic agonist specifically contraindicated in patients with history of drug abuse 1
• Phentermine/topiramate ER (Qsymia): Combination of adrenergic agonist and neurostabilizer contraindicated in patients with history of drug abuse 1
• GLP-1 receptor agonists: Already excluded per patient scenario 1

Monitoring and Follow-Up Recommendations

• Assess efficacy and safety at least monthly for the first 3 months and then every 3 months 1
• Discontinue medication if there is less than 5% weight loss at 12 weeks for orlistat 1
• For naltrexone/bupropion, discontinue if 5% weight loss is not achieved after 12 weeks at the maintenance dose 1
• Monitor for signs of substance use relapse or increased cravings 1

Lifestyle Modification Requirements

• All pharmacotherapy should be combined with an intensive lifestyle program including diet, exercise, and behavioral modification 1
• Medication should not be used alone but as an adjunct to lifestyle changes 1
• Regular follow-up through personal office visits, phone calls, texting, emails, or other communication methods is essential for success 1

Algorithm for Medication Selection

1. First attempt: Start with orlistat if patient can tolerate gastrointestinal side effects and modify fat intake
2. If orlistat is ineffective or intolerable: Consider naltrexone/bupropion if:
   • No history of seizures
   • No uncontrolled hypertension
   • No current opioid use (will be blocked by naltrexone)
   • Patient is stable in substance use recovery
3. If both options fail: Consider referral for bariatric endoscopy or surgical options 1

Remember that medication is just one component of a comprehensive weight management plan that must include dietary changes, physical activity, and behavioral modifications for long-term success 1.