Treating methamphetamine abuse disorder: Experience from research and practice

Many medications have yielded negligi­ble results in studies: selegiline, baclofen, ser­traline, topiramate, gabapentin, rivastigmine, risperidone, and ondansetron.¹⁶ Recent eval­uation of disulfiram, vigabatrin, and lobeline also has yielded inconsistent findings.¹⁷

No drug has proved effective for pre­venting relapse; research continues, focus­ing on several types of compounds that target various mechanisms: the dopamine system, the opioid system (by way of the γ-aminobutyric acid inhibitory system), and cortico-limbic reward circuitry.

Once-monthly injectable naltrexone has potential for ameliorating craving and relapse by modulating the opioid receptor system. However, the drug has not been adequately explored in generalizable set­tings of methamphetamine users.

Trials of oral naltrexone in Sweden have shown encouraging results, includ­ing reduced subjective effects and amphet­amine use in open-label trials^18,19; results were replicated in a subsequent placebo-controlled trial.²⁰ In an unpublished study, however, no differences in amphetamine use were found among users randomized to depot naltrexone or placebo.²¹

Depot naltrexone with assured dos­ing might have a role in treating metham­phetamine abuse, however; a combination of depot naltrexone and oral bupropion is being examined in a National Institute on Drug Abuse Clinical Trials Networks study that commenced in 2013. Pairing medica­tions that have different mechanistic targets might work toward promoting cessation of methamphetamine abuse and reducing relapse once patients are abstinent.

In an early phase of research, but show­ing promise based on their ability to target different systems, are:
• N-acetylcysteine, modulator of the glutamate system
• D3 antagonists and partial agonists²²
• varenicline.²³

Potential “vaccines” against metham­phetamine are in preclinical development, including use of a protein carrier or other immune-stimulating molecule to create antibodies that bind methamphetamine in the bloodstream and block its psychoactive effects.^24,25

Sigma receptor effects are being studied in rodents as potential targets to mitigate effects of methamphetamine. The ligand AZ66, a sigma receptor antagonist, has demonstrated efficacy in reducing meth­amphetamine-induced cognitive impair­ment—suggesting that the sigma receptor has a potential role in ameliorating meth­amphetamine-related neurotoxicity.²⁶

Psychosocial and behavioral interven­tions. Among the non-drug treatments that have demonstrated efficacy for treat­ing methamphetamine abuse, cognitive-behavioral therapy (CBT) and contingency management (CM) have been most widely studied and applied in treatment settings.

CBT involves individual or group coun­seling that focuses on relapse prevention skills, including identification of relapse triggers, strategies to diminish cravings, and engagement in alternative non-drug activities^27,28 (Table 3).

CM, which is based on positive rein­forcement, offers tangible reinforcers, or rewards, for behaviors (eg, clinic atten­dance, providing a drug-free urine sam­ple) according to guidelines set by the practitioner. CM-based interventions are the most reliably documented approaches for treating methamphetamine abuse,^29,30 but their utility might prove to be most efficient in combination with medication— once suitable pharmacotherapeutic options emerge.

Although CBT and CM remain accepted standard treatments for methamphetamine abuse, outcomes are suboptimal.²⁷ Both interventions have a high rate of dropout during the first month of treatment and a >50% relapse rate 6 to 19 months after treat­ment ends.^31-33

As with treatment of other substance use disorders, patients who abuse methamphet­amine can benefit from residential treatment in a drug-free setting for ≥30 days.³⁴ In the residential approach, removing access to drugs, drug cues, and drug-using acquain­tances combined with group and individ­ual counseling reaches an inevitable end: discharge into the community. Then the patient’s battle to avoid relapse begins.

Because cognitive impairment is com­mon among patients who abuse metham­phetamine, even after they stop using,³⁵ researchers have examined the potential for increasing participation in psychosocial interventions such as CBT by using medica­tions that might have potential to increase cognitive function, such as modafinil.³⁶ Increased attention and concentration afforded by medication could enhance effi­cacy of CBT. Results of trials and new drug development have been mixed³⁷; no clear candidate for preventing relapse through any of the putative mechanisms of action has emerged.

Relapse is a problematic target for treatment
Ending methamphetamine abuse and sus­taining abstinence from stimulants require a change in the cognitive associations that have been laid down in a drug user’s memory. Relapse occurs because of recalled memories that can be cued, or triggered, by internal or external stimuli. Eliminating drug memories, perhaps assisted by medi­cations such as d-cycloserine (an antago­nist of the N-methyl-d-aspartate receptor), could be useful for suppressing the inclina­tion to relapse.

Last, alternative, non-drug forms of cog­nitive amendment have shown efficacy in preventing relapse: for example, incorpo­rating mindfulness meditation, which has shown promise in managing craving for methamphetamine and decreasing reactiv­ity to environmental cues for drug use.³⁸

Bottom Line
Practitioners who work in emergency, inpatient, and outpatient settings will be called on more and more to treat acute stimulant intoxication and withdrawal, stimulant-induced psychosis, and methamphetamine abuse. Few evidence-based treatments and no FDA-approved medications are available to treat this addiction; many drugs and a few psychotherapeutic techniques have shown promise. Ongoing research promises to deliver medical and behavioral interventions to help patients quit using methamphetamine.