CATIE News

• Crystal meth use has been linked to increased HIV and hepatitis C risk among gay and bi men
• Researchers studied the effect of an anti-depressant on crystal meth dependency
• Mirtazapine was associated with modest reductions in crystal meth use over time

Crystal meth (also called ice, meth, methamphetamine, Tina) is a recreational drug that belongs to the category of drugs called stimulants. Reports indicate that among some gay, bisexual and other men who have sex with men (MSM) the use of crystal meth during sex has increased. Research among MSM suggests that, initially, this drug can cause them to experience the following:

• euphoria
• heightened sensations
• increased sex drive
• reduced inhibitions
• make other men seem more attractive

Outside of sex, both men and women report that crystal meth use heightens their sense of alertness and gives them the feeling of having more energy.

However, studies suggest that once the high from crystal meth fades, withdrawal symptoms can occur, including the following:

• anxiety
• depression
• fatigue
• prolonged difficulties with sleep

The intensity and persistence of these and other symptoms of withdrawal can vary from one person to another. Some people resume using crystal meth to resolve symptoms of withdrawal, but this can lead to dependency and health problems, including overdose.

Enter mirtazapine

The drug mirtazapine (sold as Remeron and in generic formulations) is sometimes used to treat depressive illness. Its use is associated with an increased risk of weight gain. About a decade ago, a group of scientists in San Francisco conducted a small study to explore the short-term effect of mirtazapine in users of crystal meth. This 12-week study showed a reduction in meth use among those taking mirtazapine (compared to placebo).

The same research team has now completed a longer and larger placebo-controlled study in crystal meth users. Overall, the scientists found that participants who received mirtazapine had modest reductions in crystal meth use (as assessed by urine samples). However, rates of adherence to both mirtazapine and placebo were low, around 40%. Participants who took mirtazapine had improvements in mood and sleep.

Study details

Nurses screened 241 people and found that 120 who were dependent on crystal meth and who were interested in reducing or stopping were suitable for the study.

Past research has found that when crystal meth gets into the body, it is eventually processed by the liver and partially broken down into several chemically related compounds. These compounds are then filtered by the kidneys and released into urine. In the present study, participants gave urine samples on a regular basis for analysis so that scientists could monitor their use of crystal meth.

All participants underwent brief (30 minutes) weekly counselling designed to help them understand their dependency on crystal meth and encourage their attempts to break free from its hold.

The mirtazapine and placebo pills used in the study were identical in appearance and were dispensed in containers that recorded and wirelessly transmitted information about when they were opened to the study’s central computer. This way, scientists could monitor participants’ pill-taking behaviours.

For the first week of the study, participants received mirtazapine in a dose of 15 mg/pill or matching placebo. After this, they then received mirtazapine 30 mg/pill or matching placebo. Participants were supposed to take one pill daily through week 24. After this time, pill-taking ceased but participants were monitored for a further 12 weeks.

Key participant demographics at the start of the study

• On average, participants were in their mid-40s.
• 115 participants were MSM and 5 were transgender women.
• 52% of participants were HIV positive and 16% of them had a detectable viral load.

The frequency of crystal meth use was distributed as follows:

• less than once weekly – 18% of participants
• between 2 and 4 days weekly – 31% of participants
• between 5 and 7 days weekly – 52% of participants

(Note: Percentages do not total 100 due to rounding.)

Crystal meth was taken in the following ways:

• smoked – 84%
• injection – 41%
• snorted – 38%
• inserted rectally – 28%
• ingested orally – 17%

(Many people reported more than one method of taking crystal meth.)

Results—Crystal meth use

At the start of the study, 80% of participants had urine samples that tested positive for crystal meth. This proportion declined modestly during the study, particularly among people who received mirtazapine.

Craving, dependency and other symptoms

There was no significant difference in reports of craving crystal meth by participants, whether they received mirtazapine or placebo.

At week 24, participants who were taking mirtazapine had significantly fewer symptoms of depression. There was also a trend to reduced insomnia at week 24.

Adherence

As mentioned earlier, adherence to mirtazapine and placebo were poor, averaging between 30% and 40% at different points in the study.

Safety

No major safety issues emerged. The proportions of participants who reported side effects known to be associated with mirtazapine were distributed as follows:

Fatigue or drowsiness (these categories were combined by the study team)

• mirtazapine – 30%
• placebo – 10%

Unintentional weight gain

• mirtazapine – 7%
• placebo – 2%

Increased appetite

• mirtazapine – 2%
• placebo – 2%

Bear in mind

The results from this study suggest that mirtazapine has very modest effects at reducing consumption of crystal meth in people who are dependent on it. The drug did reduce symptoms of depression.

In part, the modest effect of mirtazapine may have been driven by the poor level of adherence recorded in the study. The scientists noted that low rates of adherence have generally been reported in other studies of methamphetamine dependency.

The small amount of counselling (30 minutes weekly) is likely not optimal for people struggling with crystal meth dependency. However, the scientists used this amount of time because it is similar to what people would receive in routine care.

For the future

Future studies of mirtazapine could incorporate the following elements in order to explore their impact in people with dependency on crystal meth:

• an intensive program of adherence support
• longer and more frequent counselling appointments
• the development of a long-acting formulation of mirtazapine

Alternatively, clinical trials could explore the safety and efficacy of other potential interventions. For instance, scientists have found that an infusion of intravenous ketamine can help some people break free of cocaine dependency. It is plausible that intravenous or other formulations of ketamine could also help people dependent on meth.

Resource

Can intravenous ketamine and mindfulness therapy break cocaine dependency? – CATIE News

—Sean R. Hosein

REFERENCES:

1. Coffin PO, Santos GM, Hern J, et al. Effects of mirtazapine for methamphetamine use disorder among cisgender men and transgender women who have sex with men: A placebo-controlled randomized clinical trial. JAMA Psychiatry. 2020; in press.
2. Colfax GN, Santos GM, Das M, et al. Mirtazapine to reduce methamphetamine use: a randomized controlled trial. Archives of General Psychiatry. 2011;68(11):1168–1175.
3. Courtney KE, Ray LA. Methamphetamine: an update on epidemiology, pharmacology, clinical phenomenology, and treatment literature. Drug and Alcohol Dependence. 2014;143:11–21.
4. Dakwar E, Nunes EV, Hart CL, et al. A single ketamine infusion combined with mindfulness-based behavioral modification to treat cocaine dependence: A randomized clinical trial. American Journal of Psychiatry. 2019 Nov 1;176(11):923-930.
5. Goodnough A. A new drug scourge: Deaths involving meth are rising fast. New York Times. 17 December 2019. Available at: https://www.nytimes.com/2019/12/17/health/meth-deaths-opioids.html
6. Jones CM, Underwood N, Compton WM. Increases in methamphetamine use among heroin treatment admissions in the United States, 2008-2017. Addiction. 2020; in press.