Successful use of amantadine and levodopa benserazide in chronic portal systemic encephalopathy. A crossover trial with conventional therapy

A crossover clinical comparison of amantadine, l-dopa-benserazide and conventional therapy (protein restriction, lactulose, supportive parenteral feeding) was performed in 10 patients with cirrhosis and severe long-standing portal-systemic encephalopathy. All patients did not respond to conventional therapy. During treatment with amantadine and l-dopa-benserazide, given alone or in association, all patients showed a significant overall improvement. Even if significant progressive decrease of arterial blood ammonia was observed throughout the study, neurological improvement could be not related to reduction of hyperammonaemia. Crossover to conventional therapy produced a marked worsening in the clinical state. No serious side effect attributable to the drugs was observed. As a central dopaminergic impairment is widely accepted in the pathogenesis of hepatic encephalopathy, successful results can be related to direct and/or indirect stimulating effects on dopamine receptors. Amantadine and l-dopa-benserazide are useful adjunctive pharmacological agents that can be effectively and safely used in patients with chronic hepatic encephalopathy with a poor response to intensive conventional management. The association of both drugs can be useful in cases of impending coma.