What is the role of bupropion (Wellbutrin) in treating methamphetamine use disorder?

Bupropion in Treating Methamphetamine Use Disorder

Bupropion has limited efficacy for methamphetamine use disorder (MUD) and is not FDA-approved for this indication, but may benefit specific subgroups, particularly males with lower baseline methamphetamine use. 1

Efficacy and Evidence

Bupropion has been investigated as a potential treatment for methamphetamine use disorder based on its mechanism of action:

• It inhibits the reuptake of dopamine and norepinephrine, potentially addressing the neurochemical imbalances caused by methamphetamine use 2
• Laboratory studies have demonstrated that bupropion can reduce:
  • Acute methamphetamine-induced subjective effects
  • Cue-induced craving for methamphetamine 2

However, clinical trial results have been mixed:

• A randomized, placebo-controlled trial found no statistically significant overall effect of bupropion compared to placebo for reducing methamphetamine use 3
• Post-hoc analyses revealed potential efficacy in specific subgroups:
  • Males with lower baseline methamphetamine use showed significantly increased weeks of abstinence (p<0.0001) 1
  • Participants with lighter baseline use (0-2 positive urine tests) benefited more than heavy users (OR=2.81,95% CI=1.61-4.93, p<0.001) 3

Special Populations and Considerations

Comorbid Conditions

• In patients with comorbid PTSD and methamphetamine use disorder:
  • Bupropion showed promising results with greater reduction in PTSD symptom severity
  • Lower frequency of methamphetamine relapse (25.0% vs 48.8%)
  • Reduced hospital utilization (0% vs 29.3%) compared to traditional serotonergic agents 4

Contraindications and Precautions

Bupropion should be avoided in patients with:

• Uncontrolled hypertension
• History of seizures or conditions lowering seizure threshold
• Current use of MAO inhibitors
• Brain metastases or structural abnormalities
• Current alcohol/substance abuse (increases seizure risk) 5

Monitoring and Adverse Effects

When using bupropion for methamphetamine use disorder, monitoring should include:

• Regular blood pressure and heart rate checks, especially during the first 12 weeks 5
• Assessment for anxiety, agitation, insomnia
• Vigilance for suicidal thoughts, particularly in patients under 24 years (black box warning) 5
• Common adverse effects include insomnia, dry mouth, anxiety/jitteriness, decreased appetite, and headache 5

Dosing Considerations

• Standard dosing of bupropion SR is 150 mg twice daily 3, 1
• For patients with moderate to severe renal impairment, reduce dose by 50%
• Avoid in end-stage renal disease
• Maximum daily dose should not exceed 450 mg 5
• For hepatic impairment, lower doses are recommended 5

Clinical Application Algorithm

1. Assess baseline methamphetamine use (frequency and amount)
2. Consider bupropion primarily for:
   • Male patients
   • Those with lower baseline methamphetamine use
   • Patients with comorbid PTSD
3. Screen for contraindications (seizure history, uncontrolled hypertension)
4. Start with bupropion SR 150 mg once daily for 3 days, then increase to 150 mg twice daily
5. Combine with behavioral therapy (cognitive behavioral therapy and contingency management)
6. Monitor vital signs, particularly blood pressure and heart rate
7. Reassess efficacy after 4-6 weeks; discontinue if no benefit observed

Limitations and Future Directions

While bupropion shows promise for specific subgroups with methamphetamine use disorder, it is important to note that there are currently no FDA-approved pharmacotherapies specifically for methamphetamine use disorder 6. More research is needed to identify reliable predictors of treatment response and to develop more effective pharmacological interventions for this challenging condition.