Tyler Vanderhoof, MD PGY-4 Psychiatry Resident Department of Psychiatry and Behavioral Sciences Emory University Atlanta, Georgia
John J. Reitz, MD PGY-4 Psychiatry Resident Department of Psychiatry and Behavioral Sciences Emory University Atlanta, Georgia
Yi-lang Tang, MD, PhD Associate Professor Department of Psychiatry and Behavioral Sciences Emory University Atlanta, Georgia Addiction Psychiatrist Substance Abuse Treatment Program Atlanta Veteran Health Care System Decatur, Georgia
Disclosures The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Mirtazapineis an atypical antidepressant whose mechanism of action includes modulation of the serotonin, norepinephrine, and alpha-2 adrenergic systems. It is FDA-approved for the treatment of major depressive disorder (MDD). In a randomized placebo-controlled study, mirtazapine 30 mg/d at night was found to decrease methamphetamine use for active users and led to decreased sexual risk in men who have sex with men.35 These results were supported by an additional RCT in which mirtazapine 30 mg/d significantly reduced rates of methamphetamine use vs placebo at 24 and 36 weeks despite poor medication adherence.36 Adverse effects to monitor in patients treated with mirtazapine include increased appetite, weight gain, sedation, and constipation.
Bupropion is a norepinephrine dopamine reuptake inhibitor that produces increased neurotransmission of norepinephrine and dopamine in the CNS. It is FDA-approved for the treatment of MDD and as an aid for smoking cessation. Bupropion has been studied for methamphetamine use disorder with mixed results. In a randomized placebo-controlled trial, bupropion sustained release 150 mg twice daily was not more effective than placebo in reducing methamphetamine use.37 However, the extended-release formulation of bupropion 450 mg/d combined with long-acting injectable naltrexone was associated with a reduction in methamphetamine use over 12 weeks.38 Bupropion is generally well tolerated; common adverse effects include insomnia, tremor, headache, and dizziness.
Naltrexone.Data about using oral naltrexone to treat stimulant use disorders are limited. A randomized, placebo-controlled trial by Jayaram-Lindström et al39 found naltrexone 50 mg/d significantly reduced amphetamine use compared to placebo. Additionally, naltrexone 50 and 150 mg/d have been shown to reduce cocaine use over time in combination with therapy for cocaine-dependent patients and those dependent on alcohol and cocaine.40,41
Topiramate has been studied for the treatment of cocaine use disorder. It is hypothesized that modulation of the mesocorticolimbic dopamine system may contribute to decreased cocaine cravings.42 A pilot study by Kampman et al43 found that after an 8-week titration of topiramate to 200 mg/d, individuals were more likely to achieve cocaine abstinence compared to those who receive placebo. In an RCT, Elkashef et al44 did not find topiramate assisted with increased abstinence of methamphetamine in active users at a target dose of 200 mg/d. However, it was associated with reduced relapse rates in individuals who were abstinent prior to the study.44 At a target dose of 300 mg/d, topiramate also outperformed placebo in decreasing days of cocaine use.42 Adverse effects of topiramate included paresthesia, alteration in taste, and difficulty with concentration.
Cannabis use disorder
In recent years, cannabis use in the US has greatly increased45 but no medications are FDA-approved for treating cannabis use disorder. Studies of pharmacologic options for cannabis use disorder have had mixed results.46 A meta-analysis by Bahji et al47 of 24 studies investigating pharmacotherapies for cannabis use disorder highlighted the lack of adequate evidence. In this section, we focus on a few positive trials of NAC and gabapentin.
