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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: February 16, 2014.



Mirtazapine is a tetracyclic antidepressant with a somewhat unique mechanism of action. Mirtazapine therapy can be associated with transient asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury.


Mirtazapine (mir taz' a peen) is a tetracyclic derivative with a somewhat unique antidepressant activity in comparison to the selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. Its mechanism of action is not well defined, but it is a potent antagonist of serotonin 5-HT2 and 5-HT3 receptors and appears to enhance central noradrenergic and serotonergic (5-HT1A) activity with less activity against peripheral receptors. Mirtazapine was approved for use in moderate and severe depression in the United States in 1996 and remains in wide use, with more than 5 million prescriptions being filled yearly. The major indication for mirtazapine therapy is major depressive disorder. Mirtazapine is available as regular and oral disintegrating tablets of 15, 30 and 45 mg in multiple generic forms and under the brand name Remeron. The recommended dosage in adults is 15 mg once daily at bedtime, which can be increased to a maximum of 45 mg daily. Common side effects are drowsiness, fatigue, blurred vision, dry mouth, increased appetite and weight gain.


Liver test abnormalities have been reported to occur in up to 10% of patients on mirtazapine, but elevations are usually modest and rarely require dose modification or discontinuation. Rare instances of acute, clinically apparent episodes of liver injury with marked liver enzyme elevations with or without jaundice have been reported in patients on mirtazapine. The onset of injury has varied greatly from several months to several years. The pattern of serum enzyme elevations is usually hepatocellular, but mixed forms have also been described. Autoimmune (autoantibodies) and immunoallergic features (rash, fever, eosinophilia) are uncommon.

Mechanism of Injury

The mechanism by which mirtazapine causes liver injury is not known. Mirtazapine is extensively metabolized by the liver, mainly via the cytochrome P450 system, and hepatotoxicity may be mediated by toxic intermediates of its metabolism. In some instances, serum enzyme elevations may be due to nonalcoholic steatohepatitis triggered by weight gain caused by mirtazapine therapy.

Outcome and Management

The serum aminotransferase elevations that occur on mirtazapine therapy are usually self-limited and do not require dose modification or discontinuation of therapy. Rare instances of acute liver failure and chronic hepatitis have been attributed to mirtazapine therapy. Persons with intolerance to mirtazapine may have similar reactions to other antidepressants and careful monitoring is warranted if other such agents are used.

Drug Class: Antidepressant Agents



Mirtazapine – Generic, Remeron®


Antidepressant Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Image of Mirtazapine Chemical Structure


References updated 16 February 2014

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    (Expert review of hepatotoxicity published in 1999; no mention of mirtazapine).
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    mirtazapine has been implicated in a small number of cases).
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  • Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, Mas A, et al. Risk of acute liver injury associated with the use of drugs: a multicentre population survey. Aliment Pharmacol Ther 2007; 25: 1401-9. [PubMed: 17539979]
    (Among 126 cases of drug induced liver injury seen in Spain between 1993-2000, 3 were attributed to paroxetine and 3 to fluoxetine, with a relative risk of injury to rate of use in the population of 3.0 and 1.8 respectively; mirtazapine was not specifically mentioned).
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    (20 year old man developed asymptomatic rises in serum enzymes 3 months after starting mirtazapine [bilirubin 0.4 mg/dL, ALT 182 U/L, Alk P 131 U/L], resolving within 2 months of stopping).
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    (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, antidepressants accounted for 12 cases [4%]: duloxetine [6], buproprion [2], fluoxetine [2], amitryptiline [1], sertraline [1], but none were attributed to mirtazapine).
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  • Rodriguez-Pecci MS, Fuente-Aguado Jde L, Montero-Tinnirello J, Fernandez-Fernandez FJ. [Mirtazapine-associated hepatotoxicity]. Med Clin (Barc) 2010; 135: 625-6. Spanish. [PubMed: 19822332]
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    (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, none of which were attributed to mirtazapine).


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