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A 36-year-old man with bipolar affective disorder developed cholestasis leading to hypercholesterolaemia and pseudohyponatraemia during treatment with quetiapine, lamotrigine and zopiclone [routes not stated].
The man, who also had type I diabetes mellitus, was jaundiced on presentation and reported a 3-week history of pruritus, malaise, dark urine, pale stools and progressive abdominal discomfort. At this point he had been receiving quetiapine 400 mg/day, lamotrigine 500 mg/day and lithium for 16, 11 and 4 months, respectively; zopiclone 7.5 mg/day had been added 1 month earlier. The results of outpatient laboratory tests were suggestive of obstructive liver disease; however, the results of viral serology and autoimmune marker tests were negative. Moderate hepatosplenomegaly was noted during a gastroenterology consult, while ultrasonography performed 4 weeks after symptom onset found no biliary calculi and endoscopic retrograde cholangiopancreatography was normal. A subsequent liver biopsy revealed neutrophilic bile ductular injury.
Drug-induced cholestasis was diagnosed, quetiapine and lamotrigine were suspected and discontinued, and the man's lithium dose was increased. Six weeks post-onset, laboratory testing revealed hyponatraemia and he was hospitalised. Further investigations revealed profound hypercholesterolaemia characterised by a markedly low HDL-cholesterol and mild hypertriglyceridaemia. The cause of his hyponatraemia was not determined. However, conservative treatment with IV fluids led to an increase in his sodium level and he was discharged receiving lithium, zopiclone, colestyramine and ursodeoxycholic acid.
Six weeks later, lamotrigine was restarted without recurrence of the man's symptoms. His abnormal laboratory parameters returned to normal and colestyramine and ursodeoxycholic acid were gradually stopped. A quetiapine rechallenge was not attempted and he remained well at last follow-up. Subsequently, lipoprotein electrophoresis results indicated that lipoprotein X comprised a large proportion of plasma lipids. Lipoprotein X was considered a possible cause of his pseudohyponatraemia. Repeat lipoprotein electrophoresis results were normal 16 weeks after stopping quetiapine.Author Comment"The normalisation of laboratory parameters after quetiapine and lamotrigine were withdrawn, and the successful reintroduction of lamotrigine, favours the conclusion that quetiapine, or the combination of quetiapine, lamotrigine and zopiclone was the cause. We specify zopiclone in particular because the symptoms began around the time of its introduction".
1. Klinke JA, Shapira SC, Akbari E, Holmes DT.Quetiapine-associated cholestasis causing lipoprotein-X and pseudohyponatraemia. Journal of Clinical Pathology 63: 741-743, Aug 2010. Available from: URL: http://dx.doi.org/10.1136/jcp.2008.064063. - Canada.
Copyright Wolters Kluwer Health Adis International Sep 25, 2010