Common Antidepressant Mirtazapine Reduces Methamphetamine Use in Landmark Australia-New Zealand Study

Methamphetamine, often referred to as meth, crystal, ice, or P in New Zealand, is a potent central nervous system stimulant that leads to addiction through profound alterations in brain reward pathways. Dependence on this drug affects an estimated 7.4 million people worldwide, causing severe health issues including psychosis, cardiovascular damage, stroke, and premature death. In the absence of any approved pharmacotherapies, behavioral interventions like counseling and residential rehabilitation have been the mainstay, but relapse rates exceed 70% within a year.

The Tina Trial, registered on the Australian New Zealand Clinical Trials Registry (ANZCTR), underscores the collaborative research efforts between neighboring countries, offering hope for scalable treatments that could be integrated into routine clinical practice across the region.

Methamphetamine Crisis in New Zealand: Alarming Trends

New Zealand faces one of the highest per capita rates of methamphetamine dependence globally, exacerbated by recent surges in availability and affordability. According to the 2025 New Zealand Drug Trends Survey (NZDTS) conducted by Massey University, the street price of methamphetamine plummeted to a record low of $334 per gram, a 55% real-term drop since 2017. This decline, attributed to increased supply from Mexican cartels and Asian sources, has driven up consumption frequency, with 57% of users reporting weekly or more frequent use—nearly double the 27% in 2018.

Wastewater analysis by New Zealand Police further highlights the scale: in Q2 2025, average weekly methamphetamine consumption was 29.1 kg across monitored sites, equating to $30.5 million in social harm costs per week. By late 2025, this rose to 34.7 kg weekly, costing $32.3 million. Methamphetamine is now the second most used illicit drug after cannabis, straining healthcare, justice, and social services.

In regions like Auckland, Waikato, and the South Island, gang dominance in supply has intensified harms, including violence, mental health crises, and family breakdowns. University research plays a pivotal role in quantifying these trends and seeking solutions.

Understanding the Tina Trial: Design and Methodology

The Tina Trial was a phase 3, double-blind, placebo-controlled randomized clinical trial involving 344 adults aged 18-65 with DSM-5 diagnosed moderate to severe MUD. Participants reported methamphetamine use at least twice weekly in the prior four weeks, confirmed by positive amphetamine screens. Sites were six outpatient alcohol and drug clinics in Australia: Wollongong (NSW), Geelong (VIC), Brisbane (QLD), Perth (WA), Townsville (QLD), and Adelaide (SA).

Participants were randomized 1:1 to receive either 30 mg daily mirtazapine or matching placebo for 12 weeks, alongside standard care including self-help resources. Stratification ensured balance by sex and depression status (Patient Health Questionnaire-9 [PHQ-9] score ≥10). The primary outcome was change in self-reported days of methamphetamine use over the past 28 days, assessed via timeline follow-back at baseline, weeks 4, 8, and 12. Secondary measures included depression, insomnia (Athens Insomnia Scale), HIV risk behaviors, quality of life, and methamphetamine-negative oral fluid tests.

Adherence was monitored using medication event monitoring system (MEMS) caps, with 52% median adherence. Statistical power targeted detection of a 0.75 incidence rate ratio for methamphetamine use days.

Key Results: Significant Reduction in Use

Results were compelling: from baseline (median 24 days use/28), the mirtazapine group reduced use by a mean 7.0 days at week 12 (95% CI, -8.5 to -5.6), compared to 4.8 days in placebo (95% CI, -6.2 to -3.4)—a mean difference of 2.2 days (95% CI, -4.2 to -0.2; P=0.02). This equated to an 11% lower incidence rate ratio (0.89; 95% CI, 0.80-0.98), or 8% reduced daily risk of use.

• 86% follow-up rate at week 12.
• No significant secondary outcome differences overall, but subgroup benefits: depressed participants on mirtazapine saw greater insomnia reduction (-1.2 days; P=0.04).
• Oral fluid tests showed no group difference in abstinence, consistent with self-reports.

Effects held across sexes and depression statuses, suggesting broad applicability.

Safety and Tolerability in Real-World Settings

Mirtazapine was safe for outpatient use, with no serious adverse events linked to the drug. Common side effects included drowsiness (47% vs 33% placebo) and weight gain (10% vs 3%). Adverse event-related discontinuation was higher (23% vs 15%), but overall retention was strong. This profile aligns with known uses for depression and insomnia, positioning mirtazapine as feasible for non-specialist prescribers.

Researchers from Leading Higher Education Institutions

Lead investigator Rebecca McKetin is from the National Drug and Alcohol Research Centre at UNSW Sydney, collaborating with experts from University of Sydney, Monash University, Deakin University, University of Melbourne, University of Wollongong, and Curtin University. Steven Shoptaw from UCLA contributed international perspective. The ANZCTR registration highlights regional higher education ties.

In New Zealand, universities like the University of Auckland lead parallel efforts through the Tū Whakaruruhau study, evaluating residential methamphetamine treatment outcomes—a prospective cohort tracking health, relapse, and psychosocial factors post-18-week rehab. Massey University's NZDTS provides vital epidemiology, informing policy.

Implications for New Zealand's Treatment Landscape

With no approved MUD medications, mirtazapine offers an off-patent, low-cost (~NZ$10/week) option prescribable now under Royal Australian and New Zealand College of Psychiatrists guidelines. For NZ's ~34kg weekly consumption, integrating mirtazapine could cut harms, complementing services like Community Alcohol and Drug Services (CADS). Read the full protocol in PMC.

New Zealand Universities Driving Addiction Research

NZ higher education is at the forefront. University of Auckland's Centre for Brain Research explores meth's neurological impacts, funded by Neurological Foundation. Massey's ongoing surveys track trends, revealing 57% weekly use amid price crashes. University of Otago studies violence links, while Waikato and others assess residential rehab efficacy via Tū Whakaruruhau, aiming for culturally responsive interventions prioritizing Māori (50% recruitment target).

These efforts position NZ unis as leaders, fostering trans-Tasman collaborations like ANZCTR trials.

Challenges, Limitations, and the Path Forward

While promising, effects were modest (diluted from phase 2's 14% to 8%), impacted by low adherence and entrenched users. Self-reports, though validated, warrant caution; longer trials needed for abstinence/sustained remission. Side effects may limit uptake.

Next: Regulatory approval via TGA/Medsafe, larger trials, combination therapies. NZ researchers advocate policy shifts, including drug courts expansion amid rising harms.

Stakeholder Perspectives and Real-World Impact

Clinicians note mirtazapine's familiarity eases adoption. Patients report easier reductions, aiding psychosocial support. Policymakers eye harm minimization; unis push evidence-based funding.

Actionable Insights for Researchers, Clinicians, and Communities

1. Screen MUD patients for depression/insomnia; consider mirtazapine adjunct.
2. Monitor adherence with MEMS or apps.
3. Combine with contingency management, counseling.
4. Fund NZ trials for local efficacy.
5. Explore Māori-led interventions.

This study exemplifies higher education's role in translational research, paving the way for better outcomes in NZ's meth epidemic.

Photo by Josef Hejpetr on Unsplash