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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 26, 2020.



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 6 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 7.5, 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. Rare, but potentially severe adverse events include suicidal thoughts and behavior, activation of mania, seizures, serotonin syndrome and hypersensitivity reactions including Stevens Johnson Syndrome.


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.

Likelihood score: C (probable rare cause of clinically apparent liver disease).

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, predominantly CYP 3A4, and is susceptible to multiple drug-drug interactions with agents that induce or inhibit CYP activity. The metabolic intermediates of mirtazapine may be toxic which could account for its hepatoxicity. In other instances, serum enzyme elevations might 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


Mirtazapine 61337-67-5 C17-H19-N3 image 135204796 in the ncbi pubchem database


References updated 20 February 2020

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    (Among 179 cases of hospitalizations for unexplained acute liver injury enrolled in an Italian prospective study between 2010 and 2014, 17 had been exposed to antidepressants including citalopram [n=4], sertraline [n=3], amitriptyline [n=3] and paroxetine [n=2], and mirtazapine [n=1] and the combination of both trazodone and mirtazapine [n=1]).
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    (Using the French National Health Insurance Database, 382 serious liver injuries were found in approximately 5 million persons initiating antidepressant therapy, rates being 32.8 per 100,000 with mirtazapine, 22.2 with venlafaxine, 19.2 for SSRIs and 12.6 with duloxetine).
  • Drugs for anxiety disorders. Med Lett Drugs Ther. 2019;61(1578):121–6. [PubMed: 31386647]
    (Concise review of drugs for anxiety including SSRIs, SNRIs and benzodiazepines including mechanism of action, clinical efficacy, safety and costs; does not mention ALT elevations or hepatotoxicity).
  • Pladevall-Vila M, Pottegård A, Schink T, Reutfors J, Morros R, Poblador-Plou B, Timmer A, et al. Risk of acute liver injury in agomelatine and other antidepressant users in four European countries: a cohort and nested case-control study using automated health data sources. CNS Drugs. 2019;33:383–95. [PMC free article: PMC6441103] [PubMed: 30830574]
    (Analysis of data sources from 4 European countries identified 3.2 million persons initiating antidepressant therapy among whom there was no increased risk for acute liver injury for agomelatine compared to citalopram, an SSRI with a low rate of hepatotoxicity).
  • Schwasinger-Schmidt TE, Macaluso M. Other antidepressants. Handb Exp Pharmacol. 2019;250:325–55. [PubMed: 30194544]
    (Review of the pharmacology of antidepressants mentions that transient elevations in cholesterol and liver function tests can occur on mirtazapine therapy).
  • Drugs for depression. Med Lett Drugs Ther. 2020;62(1592):25–32. [PubMed: 32320387]
    (Concise review of the mechanism of action, clinical efficacy, safety and costs of drugs for depression; hepatotoxicity is mentioned only for nefazodone [now rarely used because of severe hepatotoxicity] and duloxetine [in heavy drinkers]).


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