Are there oral medications for the treatment of methamphetamine (meth) abuse?

Oral Medications for Methamphetamine Abuse

Currently, there are no FDA-approved oral medications for the treatment of methamphetamine use disorder, and behavioral therapies remain the primary evidence-based treatment approach. 1

Current State of Pharmacotherapy

Despite extensive research efforts, no pharmacologic treatment for methamphetamine dependence can be recommended for use in clinical practice. 1 This represents a significant gap in addiction medicine, as multiple medication trials have failed to demonstrate consistent efficacy. 2

Evidence for Specific Medications

Methylphenidate shows the most promise among tested agents, though evidence remains limited:

• Low-strength evidence from two small trials suggests methylphenidate may reduce methamphetamine use, with one study showing 6.5% versus 2.8% methamphetamine-negative urine drug screens (p=0.008, n=34) and another showing 23% versus 16% (p=0.047, n=54). 2
• Early pilot data are encouraging for D-amphetamine and methylphenidate as treatment for heavy amphetamine users, though larger confirmatory trials are needed. 3

Antidepressants as a class have been extensively studied but show no statistically significant effect on abstinence or treatment retention based on moderate-strength evidence. 2 Specifically:

• Sertraline was ineffective in proof-of-concept studies. 3
• Imipramine showed no benefit. 3

Other medications tested without benefit include:

• Ondansetron (ineffective in proof-of-concept studies) 3
• Baclofen (ineffective) 3
• Aripiprazole (actually increased amphetamine use at 15 mg/day in an outpatient pilot study) 3
• Naltrexone (insufficient evidence of benefit) 2
• Varenicline (low-strength or insufficient evidence) 2
• Atomoxetine (low-strength or insufficient evidence) 2

Treatment Recommendations

Behavioral therapies remain the mainstay of treatment for methamphetamine dependence, as they have demonstrated effectiveness where medications have not. [1, @42@]

Optimal Treatment Setting

• Intensive outpatient treatment with 3-5 visits per week of comprehensive counseling for at least the first 3 months is recommended for methamphetamine abusers. 4
• Inpatient hospitalization may be indicated for severe cases of long-term methamphetamine dependence. 4

Supportive Resources

Patients should be referred to mutual help meetings such as Narcotics Anonymous, which are appropriate for patients at any stage of readiness, including those with ongoing substance use. 1

Critical Caveats

Quality of evidence is poor: A 2023 systematic review found that evidence quality varies from low to very low on GRADE assessments, with mean sample sizes of only 27 participants and 88% male representation. 5 Many studies have high or unclear risk of bias. 2

Withdrawal management: No medication has been approved for methamphetamine withdrawal, and a comprehensive meta-analysis found insufficient evidence to indicate any medication is effective for this indication. 5

Acute intoxication management: When managing acute methamphetamine intoxication or overdose, benzodiazepines are first-line therapy for agitation, hypertension, and tachycardia—but this addresses acute toxicity, not chronic use disorder. 6

Clinical Bottom Line

Given the absence of FDA-approved medications and the low-to-moderate strength evidence showing most medications provide no benefit, clinicians should focus on intensive behavioral interventions and mutual support programs as the primary treatment modality for methamphetamine use disorder. 1, 2 Methylphenidate may be considered in select cases under specialist supervision, but this remains off-label with limited supporting evidence. 2