In the Journals

MSM, transgender women who use methamphetamine may benefit from mirtazapine

Phillip O. Coffin

Mirtazapine combined with substance use counseling may reduce methamphetamine use and certain HIV risk behaviors among cisgender men and transgender women who have sex with men, according to study findings published in JAMA Psychiatry.

“Although the impact of mirtazapine was modest, these results provide a sign of real hope for people who want to reduce or stop methamphetamine use,” Phillip O. Coffin, MD, of the San Francisco Department of Public Health, told Healio Psychiatry. “Mirtazapine, probably in combination with behavioral interventions, would be expected to help many people and opens the doors to future medication development.”

Coffin and colleagues targeted this intervention toward transgender women and men who have sex with men because methamphetamine use is prevalent among these populations and associated with considerable social and medical risks, including HIV. They noted that by facilitating the release of norepinephrine, serotonin and dopamine in brain areas associated with drug reward, craving and seeking, mirtazapine may in turn help reduce methamphetamine use and associated risk behaviors. To test this hypothesis, the researchers conducted a double-blind randomized clinical trial of mirtazapine vs. placebo in an outpatient research clinic. They included five transgender women and 115 cisgender men, all of whom dwelled in San Francisco, were sexually active with men, had methamphetamine use disorder and were actively using. Participants were randomly assigned to either the study drug or placebo for 24 weeks, with 12 additional weeks of follow-up.

Of the 120 participants, the mean age was 43.3 years, and 50.8% were white, 25.8% were African American and 12.5% were Latinx. The rate of methamphetamine-positive urine test results by week 12 significantly declined among those receiving mirtazapine vs. placebo (RR = 0.67; 95% CI, 0.51-0.87). At 24 weeks, mirtazapine was associated with reductions in positive urine results (RR = 0.75; 95% CI, 0.56-1), as well as at 36 weeks (RR = 0.73; 95% CI, 0.57-0.96), vs. placebo. According to data from a WisePill dispenser, mean medication adherence over 2 to 12 weeks among the mirtazapine group was 38.5% vs. 39.5% in the placebo group (P = .77) and over 13 to 24 weeks, it was 28.1% vs. 38.5%, respectively. The researchers noted that sexual risk behaviors did not differ significantly by study arm at 12 weeks, but those receiving mirtazapine had fewer sexual partners and fewer episodes of condomless anal sex with partners who were serodiscordant. At week 24, they had fewer episodes of condomless receptive anal sex with partners who were serodiscordant, as well as net reductions in depressive symptoms and insomnia severity. The researchers reported no serious adverse events associated with mirtazapine, and they wrote that benefits extend after treatment despite suboptimal treatment adherence.

“We were enthusiastic about mirtazapine after our previous phase 2a study,” Coffin said. “This second study, twice the size and three times the length, reaffirms the benefit we saw previously. This is an exciting step forward in being able to help people with methamphetamine use disorder.” – by Joe Gramigna

Disclosures: Coffin reports having led NIH-funded studies that received donated ledipasvir-sofosbuvir from Gilead Sciences, as well as grant or contract support from several institutions. Please see the study for all other authors’ relevant financial disclosures.

Phillip O. Coffin

Mirtazapine combined with substance use counseling may reduce methamphetamine use and certain HIV risk behaviors among cisgender men and transgender women who have sex with men, according to study findings published in JAMA Psychiatry.

“Although the impact of mirtazapine was modest, these results provide a sign of real hope for people who want to reduce or stop methamphetamine use,” Phillip O. Coffin, MD, of the San Francisco Department of Public Health, told Healio Psychiatry. “Mirtazapine, probably in combination with behavioral interventions, would be expected to help many people and opens the doors to future medication development.”

Coffin and colleagues targeted this intervention toward transgender women and men who have sex with men because methamphetamine use is prevalent among these populations and associated with considerable social and medical risks, including HIV. They noted that by facilitating the release of norepinephrine, serotonin and dopamine in brain areas associated with drug reward, craving and seeking, mirtazapine may in turn help reduce methamphetamine use and associated risk behaviors. To test this hypothesis, the researchers conducted a double-blind randomized clinical trial of mirtazapine vs. placebo in an outpatient research clinic. They included five transgender women and 115 cisgender men, all of whom dwelled in San Francisco, were sexually active with men, had methamphetamine use disorder and were actively using. Participants were randomly assigned to either the study drug or placebo for 24 weeks, with 12 additional weeks of follow-up.

Of the 120 participants, the mean age was 43.3 years, and 50.8% were white, 25.8% were African American and 12.5% were Latinx. The rate of methamphetamine-positive urine test results by week 12 significantly declined among those receiving mirtazapine vs. placebo (RR = 0.67; 95% CI, 0.51-0.87). At 24 weeks, mirtazapine was associated with reductions in positive urine results (RR = 0.75; 95% CI, 0.56-1), as well as at 36 weeks (RR = 0.73; 95% CI, 0.57-0.96), vs. placebo. According to data from a WisePill dispenser, mean medication adherence over 2 to 12 weeks among the mirtazapine group was 38.5% vs. 39.5% in the placebo group (P = .77) and over 13 to 24 weeks, it was 28.1% vs. 38.5%, respectively. The researchers noted that sexual risk behaviors did not differ significantly by study arm at 12 weeks, but those receiving mirtazapine had fewer sexual partners and fewer episodes of condomless anal sex with partners who were serodiscordant. At week 24, they had fewer episodes of condomless receptive anal sex with partners who were serodiscordant, as well as net reductions in depressive symptoms and insomnia severity. The researchers reported no serious adverse events associated with mirtazapine, and they wrote that benefits extend after treatment despite suboptimal treatment adherence.

“We were enthusiastic about mirtazapine after our previous phase 2a study,” Coffin said. “This second study, twice the size and three times the length, reaffirms the benefit we saw previously. This is an exciting step forward in being able to help people with methamphetamine use disorder.” – by Joe Gramigna

Disclosures: Coffin reports having led NIH-funded studies that received donated ledipasvir-sofosbuvir from Gilead Sciences, as well as grant or contract support from several institutions. Please see the study for all other authors’ relevant financial disclosures.