Relevance of liver enzyme elevations with four different neuroleptics: A retrospective review of 7,263 treatment courses

Data on liver enzyme elevations were collected in a retrospective study of 7,263 treatment courses with haloperidol, clozapine, perphenazine, and pera zine. Charts of 233 patients hospitalized between 1980 and 1992 at Tubingen University Psychiatric Clinic were selected because clinically relevant in creases of Liver enzymes had been detected during monotherapy with one of t he four examined neuroleptics. At least one hepatic enzyme (mostly alanine aminotransferase [ALAT]) exceeded the established reference range of 3-fold elevations of ALAT, aspartate aminotransferase, gamma -glutamyl transpepti dase, and glutamate dehydrogenase and 2-fold elevations of alkaline phospha tase (AP) during monotherapy with clozapine in 15%, perazine in 7.6%, perph enazine in 4%, and haloperidol in 2.4% of the cases. If all Liver enzyme ab normalities with any elevation greater than the conventional upper limits a re considered, incidences were as follows: clozapine, 78%; perphenazine, 62 %; perazine, 59%; and haloperidol, 50%. Testing for overall differences wit hin the four neuroleptics resulted in significantly different incidences of Liver enzyme elevations (chi (2) test, p < 0.0001). Threefold increases of AP (>540 U/L) were seen in three patients receiving haloperidol (0.3%) onl y. Twofold increases of AP (>360 U/L) were distributed as follows: clozapin e, 1%; haloperidol, 0.8%; perazine, 0.3%; and perphenazine, 0.1%. Only in t he group with 1-fold elevations of AP (>180 U/L) were the differences withi n the drug regimens significant (clozapine, 40.3%; haloperidol, 33.2%; perp henazine, 23.4%; and perazine, 23.1%; chi (2) test, p < 0.0001). In the per iod under study, no instance of icterus occurred.