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

Trial Summary

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.

What data supports the effectiveness of the drug Mirtazapine for treating methamphetamine and opioid use disorders?

Research shows that Mirtazapine can reduce methamphetamine-seeking behavior in rats and improve withdrawal symptoms in humans during amphetamine detoxification. These findings suggest it might help treat substance use disorders, although more large-scale human trials are needed. ^{1 2 3 4 5}

Is mirtazapine safe for use in humans?

Mirtazapine is generally considered safe for use in humans, with studies showing it is well tolerated in methamphetamine withdrawal treatment and amphetamine detoxification. Common mild side effects include drowsiness, headache, and nausea, and it is generally well tolerated even in cases of overdose. ^{1 2 5 6 7}

How is the drug mirtazapine unique for treating methamphetamine and opioid use disorders?

Mirtazapine is unique because it is an atypical antidepressant that works by blocking certain receptors in the brain, which may help reduce cravings and withdrawal symptoms for methamphetamine and opioids. Unlike other treatments, it does not focus on reuptake inhibition but instead enhances monoamine transmission, potentially making it effective for preventing relapse in substance use disorders. ^{1 2 4 8 9}

What is the purpose of this trial?

This project will evaluate the ability of Mirtazapine (MZP), a pharmacologically unique medication with a growing body of evidence to support its efficacy and safety for the treatment of methamphetamine (MA) use among medication for opioid use disorder (MOUD) patients, to significantly decrease MA use and related health-impairing behaviors. MZP has already successfully been used in the treatment of methamphetamine (detailed further below and in the Appendices). The investigators hypothesize that those assigned to the MZP plus treatment as usual (TAU) MZP+TAU arm will demonstrate significantly increased rates of biochemically verified abstinence from MA and other substances of abuse and experience improvements in health impairing behaviors relative to the placebo (PLO)+TAU arm across the 10-week treatment and follow-up periods.

Research Team

Sterling M McPherson, PhD

Principal Investigator

Washington State University

Eligibility Criteria

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.

My vital signs are within the normal range.

I have been diagnosed with a methamphetamine use disorder.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Mirtazapine alters cue-associated methamphetamine seeking in rats. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Treatments for methamphetamine abuse: a literature review for the clinician. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Repeated mirtazapine nullifies the maintenance of previously established methamphetamine-induced conditioned place preference in rats. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Mirtazapine in amphetamine detoxification: a placebo-controlled pilot study. [2019]

6. United States 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. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Outcomes after isolated mirtazapine (Remeron) supratherapeutic ingestions. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

A placebo-controlled trial of mirtazapine for the management of methamphetamine withdrawal. [2018]

9. Ireland pubmed.ncbi.nlm.nih.gov

Mirtazapine for the treatment of amphetamine and methamphetamine use disorder: A systematic review and meta-analysis. [2022]