Naturalistic observation on the hepatic enzyme changes in patients treated with either risperidone or olanzapine alone.
ABSTRACT This retrospective study aimed to compare differences in hepatic enzyme elevation during treatment with either risperidone or olanzapine alone in patients with psychotic disorders. The charts were reviewed for six hundred and sixty-seven (667) inpatients with psychotic disorders who were treated with either risperidone (n=289) or olanzapine (n=145) alone at a university-affiliated hospital between 1998 and 2002. Frequencies of elevation greater than the reference level in any enzyme among aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphotase (ALP) were higher in the olanzapine-treated group (26.9%) than in the risperidone-treated group (14.2%) [odds ratio (OR)=2.225, 95% confidence interval (CI)=1.362-3.638, P=0.002]. Frequencies of elevation greater than the reference level in ALT were higher in the olanzapine-treated group than in the risperidone-treated group (OR=2.182, P=0.004), as were frequencies with two-fold (OR=3.064, P=0.017) and three-fold (OR=2.883, P=0.039) elevation. Recovery time was longer in the olanzapine-treated group than in the risperidone-treated group (P=0.0059), as was latency time (P=0.0044). These results suggest that there are potential differences in antipsychotic-associated hepatic enzyme alterations between risperidone and olanzapine treatment. Controlled, prospective studies should be conducted to identify the risk factors associated with an alteration in hepatic enzymes related to treatment with risperidone and olanzapine.
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ABSTRACT: Atypical antipsychotic drugs, such as olanzapine, have been shown to alleviate the positive, negative and, to a lesser degree, the cognitive symptoms of schizophrenia in many patients. However, the detailed mechanisms of action of these drugs have yet to be elucidated. We have carried out the first investigation aimed at evaluating the effects of olanzapine treatment on the glycosylation of serum proteins in schizophrenia patients. Olanzapine treatment resulted in increased levels of a disialylated biantennary glycan and reduced levels of a number of disialylated bi- and triantennary glycans on whole serum glycoproteins. These changes were not observed on a low-abundance serum protein fraction. α1 acid glycoprotein was identified as a carrier of some of the detected altered oligosaccharides. In addition, glycan analysis of haptoglobin, transferrin, and α1 antitrypsin reported similar findings, although these changes did not reach significance. Exoglycosidase digestion analysis showed that olanzapine treatment increased galactosylation and sialylation of whole serum proteins, suggesting increased activity of specific galactosyltransferases and increased availability of galactose residues for sialylation. Taken together, these findings indicate that olanzapine treatment results in altered glycosylation of serum proteins.Journal of Proteome Research 05/2012; 11(7):3743-52. · 5.06 Impact Factor
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ABSTRACT: Systematic assessment of the prevalence and pattern of liver function test (LFT) abnormalities associated with regular antipsychotics in adult humans and consideration of management of such abnormalities. Systematic search identifying cohort, cross-sectional or case studies/series, reporting LFT abnormalities in patients receiving regular antipsychotics. EMBASE, PsychINFO, and MEDLINE were searched for studies in English from record onset. Abstracts were independently screened for eligibility by 2 researchers. Ineligible studies included those that did not report LFT reference ranges, those that studied fewer than 10 patients on a given antipsychotic, and those studying children. Key variables in group studies were extracted. Case studies/series were examined for patient outcome. Ten group studies and 91 case studies/series were eligible, although quality was poor. All groups receiving regular antipsychotics had a prevalence of LFT abnormalities greater than chance. The median percentage of patients with any abnormal LFT on any antipsychotic was 32%, with a range of 5% to 78%. The median percentage of patients with clinically significant elevations was 4%, with a range of 0% to 15%. Transaminases were most commonly elevated. Abnormalities were generally asymptomatic, arose within 6 weeks, and were either stably persistent or resolved with continued treatment. Case reports suggested that antipsychotics can be associated with severe hepatitis, fatal in a small minority of cases. Chlorpromazine is most commonly associated with acute liver injury. The LFT abnormalities in patients receiving regular antipsychotics are common but generally mild and transient. Very rarely, a severe or fatal hepatic injury can emerge.Clinical neuropharmacology 09/2012; 35(5):244-53. · 1.84 Impact Factor
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ABSTRACT: Safe prescribing practices to minimize pharmaceutically induced liver damage or worsening of preexisting conditions require knowledge about medicines with hepatotoxic potential. This paper reviews psychotropic medications and their effects on the liver. A MEDLINE search was performed utilizing the phrase "drug-induced liver injury" with various categories of psychiatric drugs. Only articles written in English were utilized. Hepatotoxicity can be acute or chronic in nature. Medication discontinuation is necessary in acute forms, while close monitoring is required in milder forms of medication-induced chronic liver damage. Nefazodone, pemoline and/or tacrine are the highest offenders. Carbamazepine and valproate products (e.g., divalproex) can lead to this adverse event and should be avoided in patients with liver disease, persons with alcohol misuse or those consuming high doses of acetaminophen. Knowing the risk levels associated with various medicines is important; prescribing multiple drugs with hepatotoxic effects should be avoided. One should educate patients about early warning signs of liver injury. Always provide clinical and laboratory monitoring before and during the use of hepatotoxic drugs. Clinical features and laboratory results govern medication prescribing with ongoing risk-to-benefit ratio assessment during pharmacotherapy.General hospital psychiatry 11/2011; 34(1):53-61. · 2.67 Impact Factor