What treatments help patients stop using methamphetamine?

Carter is a 41 year old man who comes to see you for a routine follow-up visit. He previously used cocaine on nights out with friends. Today, Carter tells you that he stopped using cocaine entirely because he found something better: crystal (methamphetamine). For the last year, he has used a little bit of crystal on weekends when he is out with friends at a bar. Initially, methamphetamine made going out and sex more fun. In the last few months, however, if he has some left over from the night before, he’ll smoke crystal in the morning to get his day started. The energy boost is helpful, but he doesn’t like the morning cravings or feeling dependent on a drug to get himself going in the morning. He asks you, “What can I do to get off meth?”

What is the most effective treatment for methamphetamine use disorder

A. Bupropion XL 450mg PO daily
B. Naltrexone 50mg PO daily
C. Contingency Management
D. Mirtazapine 30mg PO daily

You thank Carter for his candor and his desire to focus on his health. You reflect back to him what he does and doesn’t like about crystal, confirm his goal to stop using, and introduce the diagnosis of methamphetamine use disorder. 

There are, currently, no FDA approved medications for methamphetamine use disorder. Contingency management (CM) is the standard of care for the treatment of stimulant use disorders (including methamphetamine use disorder) as defined by the latest ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder. CM has a number needed to treat (NNT) of 3-5 as per one review referenced in the Curbsiders Addiction Medicine episode on stimulant use disorders. CM can also be combined with medications and other psychosocial interventions (like CBT or group therapy) to help patients meet their goals for the treatment of stimulant use disorder. 

CM works as a program by incentivizing and rewarding positive behavior change. For example, if Carter were part of a CM program and provided a urine sample that did not have methamphetamine in it, as determined by urine drug screen, he might be celebrated by program staff and participants and rewarded with a gift card to a grocery store. The goals for different CM programs or participants vary and may include complete abstinence (i.e. urine without methamphetamine), a reduction in use, coming to the clinic or making other medical appointments (e.g. cardiology clinic), or taking care of other medical problems. The rewards are commonly chances to draw from a prize bowl, sometimes called a fishbowl, that contains vouchers for money or other goods. As patients achieve more of their goals over time, they receive more draws from the fishbowl.

Access to contingency management programs is difficult, but things are improving. The US Department of Veteran Affairs has embraced CM. In 2023, California became the first state to cover CM as a Medicaid (MediCal) benefit under CalAIM (California Advancing and Innovating Medi-Cal). The Department of Health Care Services in California offers a list of available Recovery Incentives Programs by county. Consider asking a local addiction medicine colleague about regional resources for CM as the number of available programs is rapidly increasing, outpacing what’s noted online from local departments of health.

From a medication perspective, there are no FDA-approved meds for treating methamphetamine use disorder. Although most medication trials for stimulant use disorder are small with significant dropout rates, there are medications with promising signals that are used off-label for methamphetamine use disorder. We’ll focus on mirtazapine and the combination of bupropion and naltrexone today. The recently published ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder has a nice review of other agents that have been studied for methamphetamine use disorder.  

A 2020 randomized controlled trial by Coffin et al demonstrated that mirtazapine 30mg daily (vs placebo) in conjunction with weekly counseling led to a modest reduction in methamphetamine use and sexually risky behaviors over 6 months of treatment and for 3 months after the end of treatment, despite suboptimal adherence to mirtazapine (and placebo). People who took mirtazapine also saw improvements in depression and insomnia symptoms, suggesting that mirtazapine may be particularly helpful for people who struggle with methamphetamine use disorder and co-morbid depression, anxiety, or insomnia. While this trial was done in a particular subset of the population, the recommendation (supported by the ASAM/AAAP Clinical Practice Guideline) is to offer this medication to any patient whose goal is to reduce methamphetamine use. 

The 2021 ADAPT-2 trial by Trivedi et al was a larger, multisite trial that randomized people with moderate-to-severe methamphetamine use disorder to receive either placebo or a combination of extended-release injectable naltrexone (380 mg IM every 3 weeks) and bupropion XL 450mg PO daily. The medication combination significantly increased abstinence from methamphetamine with a NNT of 9. 

There is no data on the combination of ORAL naltrexone (i.e. 50mg daily) with bupropion, but the authors of the ASAM/AAAP Clinical Practice Guideline believe oral naltrexone (in combination with oral bupropion) could be similarly effective, especially in highly motivated patients who can take pills regularly. Of note, naltrexone is contraindicated for people who are prescribed or use opioids, which are sometimes used with stimulants. The naltrexone/bupropion combination therapy may also be helpful in patients with co-morbid alcohol use disorder (naltrexone), tobacco use disorder (bupropion), or depression (bupropion). There are ongoing studies looking at other treatments for methamphetamine use disorder, including buprenorphine (MURB trial) and psychedelics.

To answer Carter’s and our question above (correct answer: C), you discuss contingency management as the most effective treatment option for methamphetamine use disorder. Carter enrolls in a local CM program and has in-person visits twice a week with opportunities to draw from a fishbowl of prizes. You also review with Carter that he is up to date on STI screenings and has enough PreP, DoxyPEP, and naloxone at home. Even though Carter is not using opioids, the crystal (or equipment used with it) may have fentanyl in it, making Carter at risk for accidental opioid overdose.


Key Points

  1. There are no FDA-approved medications for methamphetamine use disorder treatment.
  2. Contingency Management (CM) is the standard of care treatment for patients with stimulant use disorders.
  3. Mirtazapine alone, and the combination of naltrexone and bupropion XL show promise as medication treatments for patients with methamphetamine use disorder.


References:

ASAM/AAAP Clinical Practice Guideline: https://downloads.asam.org/sitefinity-production-blobs/docs/default-source/quality-science/stud_guideline_document_final.pdf?sfvrsn=71094b38_1  

Coffin PO, Santos GM, Hern J, Vittinghoff E, Walker JE, Matheson T, Santos D, Colfax G, Batki SL. Effects of Mirtazapine for Methamphetamine Use Disorder Among Cisgender Men and Transgender Women Who Have Sex With Men: A Placebo-Controlled Randomized Clinical Trial. JAMA Psychiatry. 2020 Mar 1;77(3):246-255. doi: 10.1001/jamapsychiatry.2019.3655. PMID: 31825466; PMCID: PMC6990973.

De Crescenzo F, Ciabattini M, D’Alò GL, De Giorgi R, Del Giovane C, Cassar C, Janiri L, Clark N, Ostacher MJ, Cipriani A. Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis. PLoS Med. 2018 Dec 26;15(12):e1002715. doi: 10.1371/journal.pmed.1002715. PMID: 30586362; PMCID: PMC6306153.

Huxley-Reicher Z, Bach, P,  Stahl, N, Mullins, K,  Morford K, Chan, CA, “#5 Amp Up Your Treatment of Stimulant Use Disorder with Dr. Paxton Bach”. The Curbsiders Addiction Medicine Podcast. http://thecurbsiders.com/addiction, released: August 4th, 2022.

Trivedi MH, Walker R, Ling W, Dela Cruz A, Sharma G, Carmody T, Ghitza UE, Wahle A, Kim M, Shores-Wilson K, Sparenborg S, Coffin P, Schmitz J, Wiest K, Bart G, Sonne SC, Wakhlu S, Rush AJ, Nunes EV, Shoptaw S. Bupropion and Naltrexone in Methamphetamine Use Disorder. N Engl J Med. 2021 Jan 14;384(2):140-153. doi: 10.1056/NEJMoa2020214. PMID: 33497547; PMCID: PMC8111570.


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