Mirtazapine liver

A controlled trial of duloxetine (Cymbalta)—like venlafaxine a dual serotonin-norepinephrine reuptake inhibitor—in the treatment of GAD is currently underway. Anecdotal data suggests that nefazodone (Serzone) and mirtazapine (Remeron) may be effective in the treatment of GAD, though no controlled data is available. In addition, recent concerns regarding nefazodone and liver toxicity have limited this medication s utility. Please refer to Chapter 3 for more information regarding these antidepressants. 

There are reports of transient increases in liver enzymes occurring in 2% of patients receiving mirtazapine. Because of mirtazapine s wide therapeutic window, it is considered generally safe in overdose (Nelson, 1997). 

For these reasons, a mild elevation of this type during treatment with mirtazapine does not necessarily mean that the drug should be discontinued but rather that repeated monitoring should be done to determine whether it resolves. The drug should be discontinued if the elevation exceeds 3.0 times the upper limit of normal. A workup may be indicated to determine whether the elevation is symptomatic of an underlying liver disease (e.g., hepatitis C) rather than necessarily assuming it is due to mirtazapine. 

Mirtazapine is extensively metabolized in the liver, mainly by CYP1A2, CYP2D6, and CYP3A4. With once-daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in elderly people. 

Mirtazapine has been associated with increases in liver enzymes (SEDA-21,14). 

Hypothyroidism Obstructive liver disease Nephrotic syndrome Anorexia nervosa Acute intermittent porphyria Drugs Progestins, thiazide diuretics, glucocorticoids, / -blockers, isotretinoin, protease inhibitors, cyclosporine, mirtazapine, sirolimus Obesity... 

Drugs Alcohol, estrogens, isotretinoin, beta blockers, glucocorticoids, bile-acid resins, thiazides asparaginase, interferons, azole antifungals, mirtazapine, anabolic steroids, sirolimus, bexarotene Malnutrition Malabsorption Myeloproliferative diseases Chronic infectiousdiseases AIDS, tuberculosis Monoclonal gammopathy Chronic liver disease Malnutrition Obesity... 

Fluvoxamine inhibits the cytochrome P450 liver catabolic enzymes (predominantly this is inhibition of N-demethylation), leading to an increase in tricyclic antidepressant (TCA) serum levels. Plasma levels of several antidepressant drugs (e.g. amitriptyline, clomipramine, desipramine, imipramine, maprotiline, and nortriptyline) have been reported to increase by up to 4-fold during co-administration with fluvoxamine. Fluvoxamine at a daily dose of 50-100 mg causes a 3-4-fold increase in the plasma concentration of mirtazapine. 

Stormer E, von Moltke LL, Greenblatt DJ. Scaling drug biotransformation data from cDNA-expressed cytochrome P-450 to human liver a comparison of relative activity factors and human liver abundance in studies of mirtazapine metabolism. J Pharmacol Exp Ther 2000a 295 793-801. 

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