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Published Online, 23 January 2007, www.theannals.com, DOI 10.1345/aph.1H537.
 The Annals of Pharmacotherapy: Vol. 41, No. 2, pp. 359. DOI 10.1345/aph.1H537
© 2007 Harvey Whitney Books Company.
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Mirtazapine-Associated Dose-Dependent and Asymptomatic Elevation of Hepatic Enzymes

Babatunde Adetunji, MD MA MS FASAM

Clinical Assistant Professor of Psychiatry, College of Medicine, Drexel University, Attending Psychiatrist, MHM Services, MOD-2, 8001 State Road, Philadelphia, Pennsylvania 19136, fax 856/753-7615, medikhelp{at}yahoo.com

Biju Basil, MD

Attending Psychiatrist, Friends Hospital, Philadelphia

Maju Mathews, MD MRCPsych

Assistant Professor of Psychiatry, College of Medicine, Drexel University

Thomas Osinowo, MD

Assistant Professor of Psychiatry, Medical University of Ohio, Toledo, Ohio

Published Online, January 23, 2007. www.theannals.com, DOI 10.1345/aph.1H537

TO THE EDITOR: Mirtazapine is a tetracyclic piperazino-azepine antidepressant, which, according to the product package insert, has demonstrated a 2% incidence of elevated alanine aminotransferase and aspartate aminotransferase, compared with 0.3% for placebo.1 A search of MEDLINE, CINAHL, PsycINFO, Biological Abstracts, Cochrane Center of Registered Trials, and the database of Abstracts of Reviews of Effects found no reports of mirtazapine-associated, dose-dependent asymptomatic elevation of liver enzymes. The only previous report found was of 2 cases of severe and symptomatic hepatotoxicity.2 We present this case report based on the unusual nature and the lack of database indexing of this particular adverse event.

Case Report. A 20-year-old African American male who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for major depressive disorder was started on mirtazapine treatment at an initial dose of 15 mg at night, which was later increased to 30 mg at night. The patient had no significant history of substance abuse, liver dysfunction, or other medical disorders. Due to the possibility of increased cholesterol levels, a baseline diagnostic profile was obtained, which revealed normal electrolytes, urea, creatinine, lipid levels, and hepatic enzymes.

Three months after the patient began mirtazapine therapy, a repeat diagnostic profile revealed significantly elevated liver enzymes (Table 1). Physical examination revealed no abdominal or epigastric tenderness and the liver was not enlarged. Hepatitis serology was negative, and the patient denied concurrent use of herbal supplements, alcohol, or any illicit substances. Due to the effectiveness of mirtazapine in treating his depression and sleep qualities, the patient opted for a dose reduction to 15 mg per night rather than total discontinuation. Four weeks later, the enzyme levels had decreased but still remained above the normal range. The patient chose to discontinue the medication. Two months after discontinuation, liver enzymes returned to normal range. The patient refused rechallenge with mirtazapine.


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  		Table 1. Patient's Liver Enzymes Throughout Treatment

 

Discussion. Based on the temporal association of increased enzymes, lack of other identifiable causes, and a return to near-baseline enzyme levels after discontinuation, the association between mirtazapine and the raised liver enzymes in this patient is probable, according to the Naranjo probability scale.3 Although mirtazapine is an effective antidepressant, clinicians should be aware that, in addition to the possibility of elevated lipids, dose-dependent but asymptomatic elevation of liver enzymes may occur and should be monitored as part of regular follow-up.

Footnotes

Dr. Osinowo is a member of the Speaker's Bureau of Pfizer.

References

  1. Package insert. Remeron (mirtazapine tablets). West Orange, NJ: Organon USA, Inc., 2005.
  2. Hui CK, Yuen MF, Wong WM, Lam SK, Lai CL. Mirtazapine-induced hepatotoxicity. J Clin Gastroenterol 2002;35:270-1.[CrossRef][Medline]
  3. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.[Medline]




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