title: Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside.
abstract: Understanding substance use disorders (SUDs) and the problems associated with abstinence has grown in recent years. Nonetheless, highly efficacious treatment targeting relapse prevention has remained elusive, and there remains no FDA-approved pharmacotherapy for psychostimulant dependence. Preclinical and clinical investigations assessing the utility of classical antidepressants, which block monoamine reuptake, show mixed and often contradictory results. Mirtazapine (Remeron®) is a unique FDA-approved antidepressant, with negligible affinity for reuptake proteins, indirectly augments monoamine transmission presumably through antagonist activity at multiple receptors including the norepinephrine (NE)(α2), and serotonin (5-HT)(2A/C) receptors. Historically, mirtazapine was also considered to be a 5-HT(2C) antagonist, but recent evidence indicates that mirtazapine is an inverse agonist at this receptor subtype. Suggesting a promising role for mixed-action serotonergic drugs for addiction pharmacotherapy, mirtazapine attenuates psychostimulant-induced behaviors in several rodent models of substance abuse, and antagonizes methamphetamine-induced biochemical and electrophysiological alterations in rats. Preclinical findings are confirmed through published case studies documenting successful outcomes with mirtazapine therapy across a number of SUDs. To date, a large scale clinical trial assessing the utility of mirtazapine in substance abuse pharmacotherapy has yet to be conducted. However, as reviewed here, accumulating preclinical and clinical evidence argues that mirtazapine, or compounds that emulate aspects of its pharmacological profile, may prove useful in helping treat addictions.
authors.affiliation: Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Graves
authors.forename: Roueen
authors.initials: R
authors.lastname: Rafeyan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Watts
authors.forename: T Celeste
authors.initials: TC
authors.lastname: Napier
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000078785:Mirtazapine; D011985:Receptors, Serotonin / Q000187:drug effects; D019966:Substance-Related Disorders / Q000188:drug therapy*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000697:Central Nervous System Stimulants; D011985:Receptors, Serotonin; D008803:Mianserin; D008694:Methamphetamine; D000078785:Mirtazapine