The antibiotic metronidazole is now commonly used to treat portosystemic encephalopathy. We describe a patient who became psychotic while receiving this drug.

A 65-year-old white woman with Child class B liver disease secondary to homozygous (phenotype ZZ) 1-antitrypsin deficiency was treated for portosystemic encephalopathy using lactulose and metronidazole. After receiving this regimen for approximately 3 months, the patient began to show agitation, emotional lability, verbal abuse, paranoia, and manic behavior, which were witnessed by both family members and medical staff. A computed tomographic scan of the head; thyroid function tests; an electroencephalogram; and assessments of serum ammonia level, vitamin B₁₂ level, rapid plasma reagin, and serum electrolytes all showed normal results. She received a diagnosis of medicine-related organic psychosis with mania. At that time, her metronidazole level was 24 µg/mL (the steady-state plasma level is 25 µg/mL in healthy persons receiving usual therapeutic doses) [1]. Metronidazole therapy was discontinued, and the patient returned to her normal mental status after 3 days. She continued to receive all previously prescribed medications, including lactulose. At her 6-week follow-up visit, she felt well and symptoms had not recurred.

Lactulose syrup is the first line of therapy for portosystemic encephalopathy. Severe diarrhea, however, may limit its usefulness. Therefore, metronidazole may be used instead of (or in combination with) lower doses of lactulose. Metronidazole is thought to improve portosystemic encephalopathy through a reduction in the concentration of ammonia-producing bacteria in the intestine [2]. Peripheral neuropathy is one of the major side effects associated with prolonged administration of high doses of metronidazole [3]. The drug does cross the blood-brain barrier [4], a fact that probably explains the known central nervous system side effects, which include convulsions, cerebellar dysfunction, and confusion. Metronidazole metabolism is slowed in patients with cirrhosis [5], which may result in accumulation of the drug and its metabolites, although our patient did not have a toxic metronidazole level.

Altered mental status in patients with cirrhosis and portal hypertension is often due to portosystemic encephalopathy. In all such patients, physicians should aggressively attempt to diagnose and treat any precipitating causes. If metronidazole is part of the treatment regimen for a cirrhotic patient who shows evidence of psychosis or deteriorated mental status without obvious precipitating causes, withdrawal of the drug should be considered.