Can An Antidepressant Help People With Methamphetamine Addiction?

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Summary: Yes, evidence from a new study shows that a common antidepressant can help people with methamphetamine addiction, also called methamphetamine use disorder.

Key Points:

Rates of methamphetamine use, addiction, and fatal overdose have increased dramatically in recent years.
Methamphetamine addiction causes some of the most serious side effects and complications among all drugs of misuse.
Complications arising from methamphetamine include physical problems, mental health problems, disruptions in family and social relationships, and difficulty with typical daily function.

Methamphetamine Addiction: Seeking New Solutions

Given the increase in methamphetamine use and associated negative outcomes among adults in the U.S. over the past decade, finding new ways to treat methamphetamine addiction are an important goal for scientists working in addiction treatment research. Unlike alcohol use disorder (AUD) and opioid use disorder (OUD), i.e. alcohol addiction/opioid addiction, there are currently no known medications that help people with methamphetamine addiction.

That’s why a group of researchers designed a study to assess whether a common antidepressant medication called mirtazapine can help people with methamphetamine addiction. In the study “Mirtazapine for Methamphetamine Use Disorder: A Randomized Clinical Trial,” scientists from the U.S. and Australia posed this research question:

“Is mirtazapine safe and effective for methamphetamine use disorder when delivered in routine clinical practice?”

To answer the question, the research team recruited a total of 344 adults with methamphetamine addiction currently in treatment at six (6) outpatient clinics in Australia, and assigned half to an experimental group and half to a placebo group. The participants followed a simple protocol:

Both groups received baseline assessments for methamphetamine use, depression, insomnia, HIV-risk behavior, and quality of life using standard psychiatric and addiction treatment metrics.
The experimental group took 30 mg/day mirtazapine, orally, every evening for 12 weeks.
The control group took a nonactive placebo, orally, every evening for 12 weeks.
Both groups repeated initial assessments at 4 weeks, 8 weeks, and 12 weeks after study initiation.

The primary outcome researchers assessed:

Change in past 28-day methamphetamine use from trial initiation to trial week 12.

Secondary outcomes researchers assessed included:

Change in depression scores on the PHQ-9, an evidence-based depression metric.
Change in insomnia scores on the AIS-5, an evidence-based insomnia metric.
Any change in HIV-risk behavior on the OTI-HRBS, an evidence-based assessment designed to assess risk among people with opioid use disorder (OUD) but is directly applicable to people with methamphetamine use disorder.
Change in quality of life score on the Q-5D, a standard quality of life metric that includes questions on mental health, personal mobility, self-care habits, participation in typical activities, and current levels of pain and/or physical discomfort.

Data from those metrics – particularly assessment of the primary outcome, reduction in days of methamphetamine use – should provide information both necessary and sufficient to determine whether an antidepressant can help people with methamphetamine addiction. Before we look at the results on mirtazapine for methamphetamine addiction, we’ll review the basic facts related to methamphetamine addiction in the U.S.

Methamphetamine Facts and Figures: Methamphetamine Use, Addiction, Fatal Overdose, Additional Complications

We’ll start with data from the 2024 National Survey on Drug Use and Health (2024 NSDUH), an annual nationwide survey that offers insight into current trends and patterns associated with drug use and treatment for drugs of addiction, as well as information on various other addiction and mental health topics.

We’ll start with the data on methamphetamine use in the past year.

Methamphetamine Use: U.S. Adults, 2024

Total, age 18+: 2.51 million
By age group:
- 18-25: 108,000
- 26+: 2.5 million

Next, the data on methamphetamine addiction in the past year.

Methamphetamine Use Disorder: U.S. Adults, 2024

Total, age 18+: 1.8 million
By age group:
- 18-25: 71,000
- 26+: 1.7 million

Studies indicate that people with methamphetamine addiction have a higher likelihood of developing specific mental health problems:

Depression
Anxiety
Post-traumatic stress disorder
Bipolar disorder

Research also shows that, in addition to severe disruption in relationships, work, and typical daily functioning, people methamphetamine addiction and/or misuse increases risk the following negative mental health consequences and physical diseases/complications:

Paranoia
Psychosis
Substance-induced psychosis
Substance-induced schizophrenia
Bacterial infections
Viral hepatitis
HIV
Cardiovascular issues: stroke, heart failure
Decreased sexual function in males

The last set of general data on methamphetamine use we’ll share is the most serious: the data on fatal methamphetamine overdose published in a long-range study in 2025:

Fatal Methamphetamine Overdose: U.S., 2013-2023

2013 – 2019: 1.2 per 100,000 to 5.0 per 100,000

That’s and increase of over 300%

2019: 5.0 per 100,000
2020: 7.4 per 100,000
2021: 9.7 per 100,000
2022: 10.5 per 100,000
2023: 10.3 per 100,000

That’s an increase of over 100%

In individual numbers, based on the current adult population of the U.S., a rate of 10.3 per 100,000 works out to over 30,000 individual fatalities associated with methamphetamine.

Every overdose death is a preventable tragedy.

With that fact – and the figures above – in mind, let’s take a look at the results of the study we discuss in the beginning of this article.

An Antidepressant for Methamphetamine Addiction: Study Results

Spoiler alert: these outcomes contain news that offers hope for people in treatment for methamphetamine addiction.

Here’s what the research team found:

Mirtazapine vs. Placebo Methamphetamine Addiction

Primary outcome, change in past-28 day methamphetamine use at 12 weeks:

Placebo: 4.8 day reduction
Mirtazapine: 7.0 day reduction

Secondary end points:

Depression (PHQ-9):
- Placebo: 2.3 point decrease
- Mirtazapine: 2.5 point decrease
Insomnia (AIS-5):
- Placebo: 1.2 point decrease
- Mirtazapine: 1.8 decrease
HIV risk behavior (OTI HRBS):
- Placebo: 1.1 point decrease
- Mirtazapine: 1.4 point decrease
Quality of life score (EQ-5D):
- Placebo: 1.2 point decrease
- Mirtazapine: 2.2 point decrease

Here’s how the research team describes these results:

“Mirtazapine is safe and effective when used in routine clinical practice for reducing methamphetamine use in adults with methamphetamine use disorder.”

That’s not all.

Using advanced statistical analysis, the team discovered that the results for reduced methamphetamine use were not the result of reductions in mental health symptoms associated with antidepressant use or reductions in insomnia, but rather, were a direct consequence of the impact of mirtazapine on methamphetamine addiction:

“Consistent with the previous trials of mirtazapine on methamphetamine use disorder, we found that reductions in methamphetamine use were not contingent on improvements in depression or insomnia. This finding implies that mirtazapine has a direct effect on addictive processes, consistent with animal models of addiction and human preclinical research.”

The outcome suggests a daily 8 percent reduction in likelihood of methamphetamine use per day. While that may not seem like a large number to the casual reader, anyone familiar with methamphetamine addiction knows any improvement is meaningful, and may mean the difference between a successful recovery and a relapse to methamphetamine use.

That means that yes, an antidepressant can help people with methamphetamine addiction, and that mirtazapine may soon join the list of evidence-based treatment for methamphetamine addiction.

How Do We Currently Treat People With Methamphetamine Addiction?

We follow guidelines established by the Substance Abuse and Mental Health Services Administration (SAMHSA), which indicates the best and most effective treatment for methamphetamine addiction is comprehensive, integrated, and holistic. According to the American Society of Addiction Medicine (ASAM), effective treatment under this model means addressing six dimensions:

Intoxication, withdrawal, and addiction medication:

- To which we may soon add mirtazapine

Medical conditions, i.e. current state of physical health.
Psychiatric and cognitive status:
- - Co-occurring psychiatric diagnoses
  - Chronic disability
  - Trauma history
  - Psychiatric/cognitive function history
Substance-use associated risks, i.e. addressing likelihood of risky substance use and risky behavior associated with drug use
Recovery environment:
- - Ensuring the patient can function in the treatment environment
  - Ensuring patient safety in treatment environment
  - Appropriate support in treatment environment
Patient-centered approach:
- - Collaborative treatment plan that considers patient preference
  - Reducing practical barriers to care, i.e. transportation, time, integration with work or school
  - Individual level of need for help with motivation and commitment to treatment with techniques like motivational interviewing (MI) or acceptance and commitment therapy (ACT).

The most commonly available therapeutic modes that fulfill the various components of the dimensions above include:

Contingency Management (CM):

Counselors offer rewards designed to promote recovery, adhere to treatment, and achieve treatment goals.

Community Reinforcement Approach (CRA):

Counselors work with patients to address issues in their life that affect their overall wellbeing, in order to identify value in behavior unrelated to addiction.

Cognitive Behavioral Therapy (CBT):

Therapists collaborate with patients to identify and resolve cognitive distortions, which may include beliefs about themselves and that impair recovery and reinforce addiction.

The Matrix Model:

Multimodal, four-month approach that prioritizes creating an effective starting point for sustainable, long-term addiction recovery.

Medication:

The evidence we present above may mean that experts may soon consider mirtazapine the only first-line medication that helps people in treatment for methamphetamine addiction.

Ongoing Care/Support/Relapse Prevention:

A clinical treatment plan may last from two weeks to four months, but that’s only the beginning of the lifelong recovery journey. During treatment, patients and providers work together to create a realistic plan for ongoing care, relapse prevention, and emergency/crisis contingencies.

For an in-depth explanation of the most effective treatments for methamphetamine addiction, please refer to the following article on our blog:

What’s the Best Treatment for Methamphetamine Addiction?