Could mirtazapine treatment continue in a patient with slightly increased transaminases?/nA depress

Fråga: Could mirtazapine treatment continue in a patient with slightly increased transaminases?

A depressed male patient was unsuccessfully treated with Zoloft (sertraline) for one month. This drug was subsequently exchanged for Remeron (mirtazapine) at an initial dose of 30 mg/d. One day after changing antidepressant, slight increases in aminotransferases and gamma glutamyl transferase were noted (ALT 1.23 ucat/L, reference value <0.80 ucat/L; AST 0.92 ucat/L, reference value <0.80 ucat/L and GGT 1.37 ucat/L, reference value <1.30 ucat/L).

After ten days, the mirtazapine dose was increased to 45 mg/d. One week thereafter, ALT had increased further to 1.62 ucat/L, AST to 1.76 ucat/L and GGT to 1.78 ucat/L. All other test results were normal, including bilirubin (umol/L, reference value <26 umol/L).

Hepatitis serology showed signs of a previous hepatitis A, but no ongoing disease. There is allegedly no over-consumption of alcohol. The antidepressant effect of mirtazapine is satisfying.

Sammanfattning: Mild elevations in serum transaminases are seen in two percent of mirtazapine-treated patients. Although severe liver reactions have been described, they are typically reversible.

In the present case, treatment could continue, provided that liver enzymes are closely monitored.

Svar: A mild rise in serum transaminases is a well-known side effect of mirtazapine and significant elevations of ALT are observed in approximately two percent of the treated patients (1-2). Most of these patients never develop hepatic decompensation and the transaminase levels may normalise despite continuation of mirtazapine (2). However, there are several reports of severe liver reactions to mirtazapine (2-3). Typically, these reactions have been reversible, with full recovery after cessation.

In the Swedish Drug Information System, there are eighteen reports of liver reactions where a causal relationship to mirtazapine treatment has been deemed possible or probable. Although most reported reactions were characterised as severe, they all proved reversible after discontinuation of mirtazapine (3).

Slightly increased liver enzymes are often acceptable in drug treatment, but should merit close observation. In pronounced elevations prompt withdrawal is imperative (4).

In the present case, continuation of mirtazapine treatment seems justifiable. However, it should be accompanied with close surveillance of liver enzymes. We recommend renewed sampling every week for one month and less frequently for another two months. If values are not normalised by then, a further investigation of the underlying cause may be necessary, since pathologic levels were already present at initiation of mirtazapine treatment. Any significant rise in transaminases to e.g. three times the upper reference limit should cause termination of mirtazapine therapy. 1 Remeron. Produktresume (2002-12-17) 2 Hui C-K, Yuen M-F, Wong W-M, Lam S-K, Lai C-L. Mirtazapine-induced hepatotoxicity. J Clin Gastroenterol 2002;35:270-1. 3 Swedis (The Swedish Drug Information System) (cited 2003-03-17) 4 Davies DM, Ferner RE, de Glanville H, editors. Davie´s textbook of adverse drug reactions. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1998. p. 279.