A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status

A systematic review of published work concerning mirtazapine was undertaken to assess possible evidence of serotonergic effects or serotonin toxicity (ST) in humans, because drug toxicity and interaction data from human over‐doses is an useful source of information about the nature and potency of dr...

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Bibliographic Details
Published in:Human psychopharmacology 2006-03, Vol.21 (2), p.117-125
Main Author: Gillman, P Ken
Format: Article
Language:English
Subjects:
Adrenergic alpha-Antagonists - pharmacology
Animals
Antidepressive Agents - pharmacology
dual action
Humans
mianserin
Mianserin - adverse effects
Mianserin - analogs & derivatives
Mianserin - pharmacology
mirtazipine
Monoamine Oxidase Inhibitors - pharmacology
Nassa
Receptor, Serotonin, 5-HT1A - drug effects
Receptor, Serotonin, 5-HT1A - physiology
serotonin
Serotonin - secretion
serotonin toxicity
serotonin, dual action
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Summary:A systematic review of published work concerning mirtazapine was undertaken to assess possible evidence of serotonergic effects or serotonin toxicity (ST) in humans, because drug toxicity and interaction data from human over‐doses is an useful source of information about the nature and potency of drug effects. There is a paucity of evidence for mirtazapine having effects on any indicator of serotonin elevation, which leads to an emphasis on ST as an important line of evidence. Mirtazapine is compared with its analogue mianserin, and other serotonergic drugs. Although mirtazapine is referred to as a dual‐action ‘noradrenergic and specific serotonergic drug’ (NaSSA) little evidence to support that idea exists, except from initial microdialysis studies in animals showing small effects; those have not subsequently been replicated or substantiated by independent researchers. Also, new data indicate its affinity for Alpha 2 adrenoceptors is not different to mianserin. It appears to exhibit no serotonergic symptoms or toxicity in over‐dose by itself, nor is there evidence that it precipitates ST in combination with monoamine oxidase inhibitors, as would be expected if it raises intra‐synaptic serotonin levels. Mirtazapine has no demonstrable serotonergic effects in humans and there is insufficient evidence to designate it as a dual‐action drug. Copyright © 2005 John Wiley & Sons, Ltd.
ISSN:0885-6222
1099-1077
DOI:10.1002/hup.750