What medications are used to prevent methamphetamine cravings?

Medications for Preventing Methamphetamine Cravings

The combination of naltrexone plus bupropion is the most effective pharmacological intervention currently available for reducing methamphetamine cravings and use, showing significantly better outcomes than placebo in clinical trials. 1

Current Evidence-Based Options

First-Line Options:

1. Naltrexone-Bupropion Combination

   • Mechanism: Naltrexone (opioid antagonist) + Bupropion (dopamine/norepinephrine reuptake inhibitor)
   • Dosing: Extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg daily)
   • Evidence: In a rigorous double-blind trial, this combination showed a response rate of 13.6% compared to 2.5% with placebo (p<0.001) 1
   • Side effects: Gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia

2. Bupropion Monotherapy

   • Mechanism: Dopamine and norepinephrine reuptake inhibitor with stimulant properties
   • Evidence: Reduces methamphetamine-induced subjective effects and cue-induced craving 2
   • Best for: Males with low-to-moderate methamphetamine dependence 3
   • Limitations: Less effective for heavy users

Second-Line Options:

1. Methylphenidate

   • Evidence: Low-strength evidence from two RCTs showing increased methamphetamine-negative urine drug screens (6.5% vs 2.8% in one study, 23% vs 16% in another) 4
   • Limitations: Limited evidence, potential for abuse

2. Atypical Antipsychotics

   • Options: Quetiapine or olanzapine
   • Best for: Managing agitation and sleep disturbances during withdrawal 5
   • Limitations: Not specifically for craving reduction, primarily for symptom management

3. Mirtazapine

   • Dosing: 15-30 mg at bedtime
   • Best for: Addressing sleep disturbances, depression, and anxiety during withdrawal 5
   • Limitations: Primarily for symptom management rather than craving reduction

Treatment Algorithm

1. Assessment Phase:

   • Evaluate severity of methamphetamine use disorder
   • Screen for polysubstance use (especially opioids)
   • Assess for comorbid psychiatric conditions

2. Initial Treatment Selection:

   • For most patients: Trial of naltrexone-bupropion combination
   • For males with low-moderate use: Consider bupropion monotherapy
   • For patients with contraindications to above: Consider methylphenidate

3. Symptom Management:

   • For sleep disturbances: Add mirtazapine or trazodone
   • For severe agitation: Short-term use of atypical antipsychotics

4. Monitoring and Adjustment:

   • Urine drug screens twice weekly
   • Assess for side effects and medication adherence
   • If inadequate response after 6 weeks, consider alternative medication

Important Considerations

• Unlike opioid use disorder, there are no FDA-approved medications specifically for methamphetamine use disorder 6, 5
• Avoid beta-blockers in patients with recent methamphetamine use due to risk of unopposed alpha stimulation and worsening coronary spasm 6
• Benzodiazepines may be used for short-term management of severe agitation but should not be used long-term due to abuse potential 5
• All pharmacological interventions should be combined with behavioral therapy, particularly cognitive-behavioral therapy and contingency management 5

Pitfalls to Avoid

• Avoid prescribing pseudoephedrine-containing products as they can be diverted to manufacture methamphetamine 5
• Monitor cardiovascular parameters closely when using medications that affect blood pressure, as methamphetamine use increases cardiovascular risks 5
• Don't expect complete abstinence with medication alone - even the most effective pharmacotherapy (naltrexone-bupropion) shows modest response rates
• Be aware that many patients with methamphetamine use disorder have polysubstance use that may require additional targeted treatments

Remember that while pharmacotherapy can help reduce cravings, comprehensive treatment including behavioral interventions is essential for long-term recovery from methamphetamine use disorder.