Mirtazapine Linked to Reduced Methamphetamine Use

by William Yates, M.D. in Brain Posts

Molecular Model of MirtazapineMethamphetamine abuse and dependence are often resistant to treatment intervention with high relapse rates.  Pharmacological augmentation of behavioral treatments may provide one strategy to improve the outcome of methamphetamine addiction.Potential mechanisms for pharmacological augmentation in methamphetamine abuse include reduction id drug craving, blocking the hedonic effect of drug use, reducing dysphoria during methamphetamine withdrawal or treatment of underlying psychiatric disorders such as anxiety and mood disorders.No drug is currently approved for methamphetamine abuse--this is unfortunate given that pharmacological options exist for alcohol, nicotine and opioid abuse.Mirtazapine, a generically available antidepressant drug (Trade name Remeron) facilitates the release of several CNS monoamines including norepinephrine, serotonin and dopamine.  It has relatively low impact on sexual function.  It's primary drawback has been a tendency to increase appetite and increase weight.  Since many methamphetamine abusers are underweight, this adverse effect may be less problematic.Colfax and colleagues recently published a small randomized placebo-controlled clinical trial of mirtazapione in methamphetamine abuse.  The key elements of the clinical trial include:Diagnosis: methamphetamine dependence by DSM-IV-TR criteriaUrine drug testing positive for methamphetamine metabolitesNo acute medical or psychiatric illnessNo current major depressionNo recent use of antidepressant drugsClinical trial drug: mirtazapine 30 mg or placebo for 12 weeksOutcome measure: methamphetamine urine drug testsThis clinical trial focused on a group of male methamphetamine abusers who have sex with men.  This demographic group is known to have increased risk for sexually transmitted disease including HIV making treatment advances important.Methamphetamine-positive drug urine sample rates in the active mirtazapine drug assigned group dropped from 73% at baseline to 44% at study end.  The placebo group had no significant change with 67% positivity at baseline and 63% positivity at study end.The research team noted that the efficacy of mirtazapine for methamphetamine use seemed to be independent of any antidepressant effect.  The study participants reported only fair adherence to the study drug during the trial.  The authors note this might indicate the effect of mirtazapine might be greater in groups with higher adherence.  The mediocre adherence does underscore a hurdle for any pharmacologic intervention in those with methamphetamine abuse.This clinical trial was relatively small with thirty subjects in the mirtazapine group and thirty subjects in the placebo group.  Additionally, generalizability is limited due to the restricted demographic profile of the study group.   However the magnitude of reduction in methamphetamine-positive drug rates in the mirtazapine is impressive.   Mirtazapine holds promise as a potential new strategy for methamphetamine abuse, but the results of this study will need confirmation before wide adoption in clinical practice.Molecular model of mirtazapine from the Creative Commons file at Wikipedia authored by Ben Mills.Colfax GN, Santos GM, Das M, Santos DM, Matheson T, Gasper J, Shoptaw S, & Vittinghoff E (2011). Mirtazapine to reduce methamphetamine use: a randomized controlled trial. Archives of general psychiatry, 68 (11), 1168-75 PMID: 22065532... Read more »