Safety of Intravenous Methamphetamine in Patients Taking Mirtazapine: A Two-Site Phase 1b Randomized Controlled Trial.

Abstract

Background: There are no approved medications to treat methamphetamine use disorder. We conducted a phase 1b, inpatient,randomized, double-blind, placebo-controlled, within-subject crossover study to evaluate the safety of mirtazapine, a potential treatment for methamphetamine use disorder with positive phase 2 trial findings, in people receiving intravenous methamphetamine.

Methods: Participants received mirtazapine 30 mg or placebo daily for 5 days, underwent an intravenous methamphetamine 30 mg challenge on day 5, followed by 2 days of washout, and then switched to the other study arm and received a second methamphetamine infusion at day 12. We monitored participants for adverse events, cardiovascular effects, and pharmacokinetics.

Results: Participants (N = 15; 12 with no opioid use and 3 on methadone maintenance treatment) reached steady state mirtazapine levels before methamphetamine infusions. During the mirtazapine phase, participants reached methamphetamine peak plasma concentration 0.26 hours earlier than the placebo phase ( P = 0.02); no other impacts on methamphetamine pharmacokinetics were observed. Mirtazapine neither attenuated nor enhanced the expected cardiovascular effects of methamphetamine, including in participants receiving methadone maintenance therapy. Adverse events were similar between mirtazapine 30 mg and placebo.

Conclusions: Mirtazapine 30 mg was safe and well-tolerated in people receiving a clinically relevant intravenous methamphetamine challenge, supporting further development of this medication for the treatment of methamphetamine use disorder.