Medications for Methamphetamine Use Disorder
Mirtazapine, an existing antidepressant, fills a therapeutic void in addiction.
Posted May 1, 2026 | Reviewed by Hara Estroff Marano
Methamphetamine use disorder (MUD) remains one of the most underserved disorders in addiction medicine, largely because there are no FDA-approved medications for its treatment—yet. The 2024 National Survey on Drug Use and Health (NSDUH) estimates that approximately 2.4 million people in the United States used methamphetamine in the past 12 months.
Common street names for methamphetamine include white cross, speed, crank, ice, and chalk. Slang terms describing methamphetamine intoxication or patterns of use include tweaking (prolonged use with agitation and insomnia ), zooming, spun out, or scattered. Terms like hot rolling and foiling (inhaling vapors from heated meth on foil) may be used in some regions. "Chicken flipping" refers to the combined use of methamphetamine and heroin.
While it is impossible to know how many people learned about methamphetamine use for the first time through Breaking Bad , the show introduced the meth business to millions of viewers and brought crystal meth into the national conversation. Some critics argued that the show's intense focus on meth, even when depicting its horrors, could have triggered curiosity among some viewers.
But, Breaking Bad functioned as an unusually effective form of popular-culture public health messaging—not a formal prevention campaign but more influential than many. Walter White was not initially a stereotypical user/dealer, but his trajectory demonstrated the initial sense of perceived control leading to loss of control and progressive loss of family, identity , and safety—accumulating consequences that seemed irreversible. The writer, producer, and staff received Drug Enforcement Administration (DEA) awards for drug education and prevention.
Methamphetamine use, addiction, and overdose deaths have risen sharply since the mid-2010s. Stimulant -related deaths—often involving co-use with fentanyl—highlight a major treatment gap: There are currently no FDA-approved pharmacologic treatments for stimulant use disorders. Against this backdrop, a new randomized clinical trial of mirtazapine (Remeron) exclusively in six outpatient alcohol and other drug clinics in Australia, conducted by Dr. Rebecca McKetin, is remarkable .
This phase-3, multisite, pragmatic trial was designed to evaluate mirtazapine's effectiveness in routine outpatient treatment. Approximately 344 participants with methamphetamine use disorder were randomized to mirtazapine 30 mg daily or placebo for 12 weeks. The primary outcome—reduction in days of methamphetamine use—was statistically significant, favoring mirtazapine by 2.2 fewer days per 28-day drug use than placebo.
Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) that is unusually broad-spectrum. Its importance lies not in delivering a game-changing medication like Ozempic for type-2 diabetes. Rather, mirtazapine provides the clearest evidence to date that a widely available antidepressant can reduce methamphetamine use.
With MUD, especially in the setting of polysubstance use, even small reductions in frequency may translate into fewer overdoses and fewer infectious complications and improved engagement with care. In a field defined by therapeutic scarcity, modest but reproducible progress is highly meaningful.
MUD Is Rarely Just Meth
Methamphetamines suppress fatigue but also reduce judgment, increase impulsivity, and promote violence. Polysubstance use is the rule rather than the exception in methamphetamine use disorder, with frequent co-use of opioids, alcohol, cannabis, nicotine, and other drugs. About 90% of meth users report polysubstance use, with an average use of 3.3 substances.
Polysubstance use is associated with greater medical risks. In psychostimulant overdose deaths, ~50% also involve opioids. Compared to single-drug use, meth plus opioid co-use is associated with a 132% increase in injection drug use, approximately double the risk of infectious diseases, triple criminal justice involvement, and markedly higher medical, neurological, and psychiatric consequences.
People with MUD are challenging to treat, as they often cycle through binge use, paranoid delusions, auditory/visual hallucinations, agitation, irritability, withdrawal, dysphoria, depression , insomnia, and relapse . Continued use is often driven as much by attempts to regulate their physical symptoms as by obtaining a high from the drug. Mirtazapine counters physiologic disruptions characteristic of chronic stimulant use and acts as a neurobiological stabilizer. It helps with sleep deprivation, hyperarousal, and dysphoria—all MUD characteristics.
In some cases, methamphetamine use may reflect attempts to self-manage psychiatric conditions. But in severe stages of illness, polysubstance use is less goal-directed and increasingly driven by drug availability, withdrawal avoidance, and compulsive use.
Some individuals purposely combine methamphetamine, a stimulant, with opioids (depressants) to modulate stimulant effects and mitigate mood crashing. Others use multiple stimulants, often reflecting tolerance, binge patterns, or availability rather than a deliberate pharmacologic strategy. A third use pattern involves alcohol or benzodiazepines to manage anxiety , insomnia, and post-stimulant dysphoria caused by methamphetamine, producing a cyclical pattern of stimulation and sedation.
Methamphetamine users have a five-fold higher involvement in crime , including violent crimes such as assault and weapon offenses, during months when they are actively using, compared to when they are not. NSDUH data show that more than two-fifths (42%) of individuals with MUD report being arrested for any offense in the past year.
Seen in this light, the McKetin results are important, because mirtazapine may help with sleep disturbances, anxiety, and mood instability. Using mirtazapine would be preferable to self-medicating with alcohol, cannabis, or other illegal drugs.
How Mirtazapine Compares
The strongest medication evidence for MUD remains the combination of extended-release injectable naltrexone and bupropion, first demonstrated in the 2021 ADAPT-2 (Accelerated Development of Additive Pharmacotherapy Treatment) clinical trial and supported by later analysis showing continued reductions in methamphetamine use over 12 weeks. In the 2024 extended observational analysis , participants receiving naltrexone and bupropion had a 27.1% increase in methamphetamine-negative urine tests over 12 weeks, compared with 11.4% in the placebo group. However, absolute response rates remain low. Also, some physicians are reluctant to prescribe naltrexone, especially in an injectable form.
In contrast, mirtazapine’s value lies in its availability, reliability, and safety in outpatients. The 2026 McKetin trial found that mirtazapine 30 mg/day reduced methamphetamine use by about two additional days per 28-day period compared with placebo, without safety concerns. This is a reproducible regimen that is easy to implement clinically.
Also, mirtazapine is inexpensive, familiar to clinicians, requires no induction protocol, and can be prescribed in primary care, outpatient, or residential treatment (RTC) settings. Appalachian Kentucky was at the epicenter of the prescription opioid epidemic in the early 2000s, which evolved into the "twin epidemic", in which individuals are using both methamphetamine and opioids, requiring specialized care to address both addictions. People with MUDs need treatment rather than just incarceration; Kentucky leads the nation in RTC beds per capita.
RTCs remain one of the few interventions capable of safely removing the MUD/polysubstance-using patient from a high-risk, cue-rich environment, evaluating and treating a range of problems, stabilizing the person by removing access to substances, and, over time, restoring basic physiologic rhythms. But without continuity of care, step-down intensive outpatient treatment, pharmacologic support, and recovery-oriented self-help programs, gains achieved in residential settings often evaporate after discharge, reflecting reintroduction of the same environmental and neurobiological pressures that drove initial drug use.
Recent evidence (2024-2026) supports a layered treatment model rather than a single-medication approach for treating MUD or polysubstance addictions. Initial management may require hospitalization or residential care. Contingency management remains the behavioral standard of care, with cognitive-behavioral therapy (CBT), exercise, and other therapies supporting durable behavior change. Pharmacologic treatments for MUD are adjunctive: Mirtazapine may improve sleep, appetite , mood, and physiologic dysregulation, while naltrexone-bupropion targets reward-driven stimulant use. Emerging therapies, including GLP-1 receptor agonists, may modulate cross-substance reward, but for now, they remain investigational rather than established.
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This article is part of the Bringwise Psychology Journal — daily insights on human behavior, mental health, and personal growth.