Mirtazapine for Methamphetamine and Opioid Use Disorders

(MIRROM Trial)

Overseen By Serena M McPherson, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington State University

Must be taking: Methadone, Buprenorphine/Naloxone

Must not be taking: Antidepressants, Phenytoin, Carbamazepine, others

Disqualifiers: Dementia, Severe liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Mirtazapine to determine if it can help reduce methamphetamine use in individuals also receiving treatment for opioid use disorder. The trial aims to assess whether Mirtazapine can aid in abstaining from methamphetamine and improve health behaviors compared to a placebo. Participants will be divided into two groups: one receiving Mirtazapine with their usual treatment, and the other receiving a placebo with the same treatment. Individuals enrolled in a methadone or buprenorphine program for opioid use disorder who also have a methamphetamine use disorder may be suitable for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including any antidepressants within the past 30 days, and specific medications like phenytoin, carbamazepine, or cimetidine. If you are currently taking any opioid use disorder medication other than methadone or buprenorphine/naloxone, you would also need to stop those.

Is there any evidence suggesting that Mirtazapine is likely to be safe for humans?

Research has shown that Mirtazapine is generally safe for people. Studies have found it to be well-tolerated when used to help reduce methamphetamine use. In one study, participants who took Mirtazapine had fewer positive urine tests for methamphetamine, suggesting the drug helps reduce drug use without causing major side effects. Another study confirmed that Mirtazapine was well-tolerated even when used with methamphetamine in a controlled setting, with no reports of serious side effects. Although the treatment is still being tested for methamphetamine use disorder, these findings suggest it has a promising safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for methamphetamine use disorder?

Unlike the standard treatments for methamphetamine and opioid use disorders, which often involve therapies like methadone or buprenorphine, mirtazapine offers a unique approach by acting as a noradrenergic and specific serotonergic antidepressant. Researchers are excited because mirtazapine targets neurotransmitter systems differently, potentially improving mood and reducing cravings simultaneously. This dual action could make it a promising option for individuals who struggle with both substance use and mood disorders, offering a new avenue of hope where traditional methods may fall short.

What evidence suggests that Mirtazapine might be an effective treatment for methamphetamine use disorder?

Research has shown that mirtazapine, an antidepressant, can help reduce methamphetamine use. In one study, combining mirtazapine with counseling led to less methamphetamine use and fewer risky sexual behaviors. Another study found that mirtazapine reduced methamphetamine use over a 24-week treatment period and maintained these reductions for 12 weeks afterward. Importantly, a review of several studies confirmed that mirtazapine reduces methamphetamine use without affecting depression symptoms. Overall, increasing evidence supports mirtazapine's effectiveness in treating methamphetamine use. In this trial, participants will receive either mirtazapine combined with treatment as usual (MZP+TAU) or a placebo combined with treatment as usual (PLO+TAU). ^{1 3 4 5 6}

Who Is on the Research Team?

Sterling M McPherson, PhD

Principal Investigator

Washington State University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with methamphetamine use disorder who are already enrolled in opioid treatment programs. They must have stable vital signs, a confirmed diagnosis of methamphetamine use disorder, and at least one positive drug test for methamphetamines. Participants need to show they can stick to the treatment plan and be generally healthy without serious illnesses.

Inclusion Criteria

I am enrolled in a treatment program for opioid use at Oregon Recovery & Treatment Center or in Spokane, WA.

I have been diagnosed with a methamphetamine use disorder.

I can sign and understand the consent form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Mirtazapine or placebo along with treatment as usual for methamphetamine use disorder

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including abstinence from methamphetamine and other substances

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirtazapine

Trial Overview The study tests if Mirtazapine helps reduce methamphetamine use among patients receiving opioid addiction treatments compared to a placebo. It's designed to see if those taking Mirtazapine plus usual care show better abstinence from drugs and improved health behaviors over a 10-week period than those on placebo.

How Is the Trial Designed?

Group I: MZP+TAU Experimental Treatment 1 Intervention

Mirtazapine + Treatment as Usual

Group II: PLO+TAU Placebo Group 1 Intervention

Placebo + Treatment as Usual

Mirtazapine is already approved in United States, European Union for the following indications:

Approved in United States as Remeron for:

• Major depressive disorder

Approved in European Union as Avanza for:

• Major depressive episodes

Who Is Running the Clinical Trial?

Washington State University

Lead Sponsor

Trials

114

Recruited

58,800+

Published Research Related to This Trial

In a double-blind, randomized placebo-controlled trial involving 31 participants, mirtazapine did not significantly improve retention or alleviate withdrawal symptoms in individuals undergoing methamphetamine withdrawal, compared to a placebo.

Despite the lack of significant differences in treatment outcomes, the study highlights the need for further exploration of narrative therapy as a supportive intervention for patients with methamphetamine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal. Cruickshank, CC., Montebello, ME., Dyer, KR., et al.[2018]

Mirtazapine, an FDA-approved antidepressant, shows promise in treating substance use disorders (SUDs) by reducing psychostimulant-induced behaviors in animal models and has been associated with positive outcomes in case studies.

Despite its potential, there is currently no large-scale clinical trial confirming the efficacy of mirtazapine for addiction treatment, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside. Graves, SM., Rafeyan, R., Watts, J., et al.[2021]

There are currently no effective pharmacotherapy options identified for enhancing abstinence in methamphetamine (METH) dependence, as reviewed across various medications including sertraline, bupropion, and aripiprazole.

Despite aripiprazole being the most frequently studied medication, no single treatment showed consistent efficacy due to methodological limitations in the trials reviewed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatments for methamphetamine abuse: a literature review for the clinician. Brackins, T., Brahm, NC., Kissack, JC.[2013]

Mirtazapine may lead to a small reduction in methamphetamine use after 12 weeks compared to a placebo, based on data from two randomized controlled trials involving 180 participants.

However, mirtazapine does not appear to improve treatment retention or reduce depression symptoms in individuals with amphetamine use disorder, and no serious adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirtazapine for the treatment of amphetamine and methamphetamine use disorder: A systematic review and meta-analysis. Naji, L., Dennis, B., Rosic, T., et al.[2022]

A retrospective review of 33 isolated mirtazapine ingestions showed that overdoses are generally well tolerated, with the most common symptoms being drowsiness and lethargy, and no reported deaths.

Among the 23 patients with recorded symptoms, cardiovascular effects were noted in 4, including tachycardia in 3 patients, indicating that while mirtazapine overdoses can cause some cardiovascular symptoms, they are not severe in most cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions. LoVecchio, F., Riley, B., Pizon, A., et al.[2022]

In a rat study, repeated administration of mirtazapine (10 doses) effectively inhibited the expression of methamphetamine-induced conditioned place preference, suggesting its potential to counteract the effects of methamphetamine addiction.

A single injection of mirtazapine did not have the same effect, indicating that the duration and timing of treatment are crucial for mirtazapine's efficacy in addressing the consequences of methamphetamine withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated mirtazapine nullifies the maintenance of previously established methamphetamine-induced conditioned place preference in rats. Voigt, RM., Mickiewicz, AL., Napier, TC.[2021]

In a 14-day pilot trial with 20 participants undergoing amphetamine detoxification, mirtazapine significantly reduced withdrawal symptoms compared to placebo, particularly in hyperarousal and anxiety, with improvements noted at both 3 and 14 days.

While mirtazapine showed promise in alleviating withdrawal symptoms, it did not significantly impact depression levels, and mild side effects like headache and sedation were reported, indicating a need for further research despite its potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirtazapine in amphetamine detoxification: a placebo-controlled pilot study. Kongsakon, R., Papadopoulos, KI., Saguansiritham, R.[2019]

Mirtazapine significantly reduced methamphetamine-seeking behavior in rats by approximately 50% during tests involving cues associated with methamphetamine, suggesting its potential as a treatment to prevent relapse in substance abuse disorders.

The study demonstrated that mirtazapine did not impair motor performance at the effective dose, indicating its safety profile in this context while providing preclinical evidence for its efficacy in reducing drug-seeking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirtazapine alters cue-associated methamphetamine seeking in rats. Graves, SM., Napier, TC.[2021]

In a study comparing the safety and tolerability of modafinil (400 mg/day) and mirtazapine (60 mg/day) in treating methamphetamine withdrawal, both medications were found to be well tolerated with mild and transient side effects, such as headaches for modafinil and aches for mirtazapine.

Modafinil resulted in a milder withdrawal syndrome and less sleep disturbance compared to mirtazapine and a historical group treated with pericyazine, suggesting it may be more effective in alleviating withdrawal symptoms, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptoms and sleep patterns during inpatient treatment of methamphetamine withdrawal: a comparison of mirtazapine and modafinil with treatment as usual. McGregor, C., Srisurapanont, M., Mitchell, A., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11193254/

A phase 3 randomised double-blind placebo-controlled trial of ... Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3437988/

Mirtazapine to Reduce Methamphetamine Use The addition of mirtazapine to substance use counseling decreased methamphetamine use among active users and was associated with decreases in sexual risk ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871625002224

Mirtazapine reduces hypothetical methamphetamine ... A meta-analysis concluded mirtazapine reduces methamphetamine use but does not change depression symptom ratings (Naji et al., 2022). The ...

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2757018

Effects of Mirtazapine for Methamphetamine Use Disorder ... Findings In this analysis, mirtazapine reduced the use of methamphetamine over 24 weeks of treatment and 12 weeks of follow-up after treatment ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06323837

Mirtazapine for the Treatment of Methamphetamine Use in ... This project will evaluate the ability of Mirtazapine (MZP), a pharmacologically unique medication with a growing body of evidence to support its efficacy and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04614584?term=METHAMPHETAMINE&rank=2

Mirtazapine and Methamphetamine Drug-drug Interaction ... This is a drug-drug interaction (DDI) study of mirtazapine for methamphetamine (MA) use disorder (MUD) to ensure the safety of this medication in the presence ...