Hepatic Effects

Acute hepatitis has been associated with administration of imipramine (Horst et al. 1980; Moskovitz et al. 1982; Weaver et al. 1977) and desipramine (Powell et al. 1968; Price and Nelson 1983). Mild increases of liver enzymes (less than three times normal) are not uncommon and usually can be monitored safely over a period of days or weeks without apparent harmful consequences. These changes in liver enzymes do not appear to be related to drug concentrations (Price et al. 1984). Acute hepatitis is relatively uncommon but can occur. The etiology is not well established but in some cases appears to be a hypersensitivity reaction. It is characterized by very high enzyme levels (e.g., aspartate aminotransferase [AST] levels >800), which develop within days. The enzyme pattern can be either hepatocellular or cholestatic. Enzyme changes may precede clinical symptoms, especially in the hepatocellular form. If a random blood test indicates mildly elevated liver enzymes, enzyme levels can be followed for a few days. Because of the rapid rise in liver enzyme levels in acute hepatitis, that condition will become evident quickly and will be easily distinguished from mild, persistent enzyme level elevations.

Acute hepatitis is a dangerous and potentially fatal condition. The antidepressant must be discontinued and should not be introduced again because the next reaction may be more severe. Unfortunately, it is not uncommon for the patient to be receiving several medications, so that the offending agent may be hard to identify. The risk of severe drug-induced hepatitis is not well established. This author has observed four cases associated with desipramine in the course of treating approximately 500 patients.

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