High incidence of multisystemic reactions to zimeldine

Forty-five patients suffering from a major depression were administered zimeldine, amitriptyline or placebo (15 patients in each group) in a double-blind controlled study. In the zimeldine group, seven of the 14 patients treated for more than one week presented a toxic syndrome consisting in a severe prostration, fever, myalgias and arthralgias. In all patients presenting this syndrome, laboratory analyses revealed an elevation of alkaline phosphatase and of aspartate and alanine aminotransferases and a decrease in white blood cell and platelet counts. Three patients presented a mild proteinuria and hematuria. Although an immunological mechanism cannot be ruled out, several characteristics of this reaction suggest the formation of a metabolite of zimeldine with direct cellular toxicity. The relatively high starting dose of 200 mg/day of zimeldine administered in the present study and the increment to 300 mg/day after only seven days might have contributed to the high incidence of toxic reactions observed.