Toxic hepatitis and single daily dosage imipramine therapy

Liver function abnormalities have occasionally been associated with imipramine since the drug was introduced in 1957. The mechanism by which the drug produces hepatotoxicity has not been determined but may involve a direct toxic effect or a hypersensitivity reaction. In this case, a patient receiving 6 mg/kg (300 mg) of imipramine daily developed elevated liver enzymes while the plasma imipramine concentration was found to be in a therapeutic range. This case suggests that single daily dosing of tricyclic antidepressants may be more hazardous to the liver than divided doses.