Case report: Valproic acid and risperidone treatment leading to development of hyperammonemia and mania
ABSTRACT This case report describes two children who developed hyperammonemia together with frank manic behavior during treatment with a combination of valproic acid and risperidone. One child had been maintained on valproic acid for years and risperidone was added. In the second case, valproic acid was introduced to a child who had been treated with risperidone for years. In both cases, discontinuing the valproic acid resulted in normalization of ammonia levels and cessation of the manic behavior. This case report alerts physicians to the importance of obtaining serum ammonia levels in children treated with valproic acid and risperidone who present with manic behavior.
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ABSTRACT: Hyperammonemia is one of the side effects of treatment with valproic acid (VPA), but the risk factors and mechanisms involved remain obscure. This study analyzed the risk factors for hyperammonemia associated with VPA therapy in adult epilepsy patients. A retrospective analysis of 2724 Japanese patients (1217 males and 1507 females aged from 16 to 76years) treated with VPA between January 2006 and December 2010 were analyzed. The ammonia level increased markedly in a VPA dose-dependent manner, and was significantly elevated in patients who also used hepatic enzyme inducers such as phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ), and combinations of these drugs. When a blood ammonia level exceeding 200μg/dl was defined as hyperammonemia, the risk factors for hyperammonemia according to multiple regression analysis were a VPA dose >20mg/kg/day (odds ratio (OR): 4.1; 95% confidence interval (CI): 1.6-10.8) and concomitant use of PHT (OR: 11.0; 95% CI: 3.1-38.7), concomitant PB (OR: 4.3; 95% CI: 1.0-17.9), concomitant CBZ (OR: 2.8; 95% CI: 0.6-11.9), and concomitant topiramate (OR: 2.8; 95% CI: 1.2-6.5). Regimens containing multiple inducers were associated with an increased risk of hyperammonemia. Identification of risk factors for hyperammonemia associated with VPA therapy can help to minimize side effects during its clinical use.Epilepsy research 04/2012; 101(3):202-9. DOI:10.1016/j.eplepsyres.2012.04.001 · 2.19 Impact Factor
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ABSTRACT: Valproate (VPA)-induced hyperammonemic encephalopathy (VHE) is a serious drug-related adverse effect characterized by lethargy, vomiting, cognitive slowing, focal neurological deficits and decreased levels of consciousness ranging from drowsiness to coma. We present a case series (n=5) and also review previous cases of VHE (n=30) in psychiatric patients to provide an update on risk factors, clinical correlates and management of VHE. To our knowledge, there are 30 (16 female, 14 male) previously reported VHE cases in psychiatric patients. Risk factors for VHE include VPA-drug interactions, mental retardation, carnitine deficiency and presence of urea cycle disorders. Length of VPA treatment, VPA dosage, serum VPA levels and serum ammonia levels do not appear to correlate with onset or severity of VHE.VPA discontinuation is the primary treatment of VHE, although, l-carnitine, lactulose and neomycin have been used adjunctively in some patients. Clinicians should consider VHE in patients taking VPA who present with lethargy, gastrointestinal symptoms, confusion and decreased levels of drowsiness. VPA discontinuation is currently the mainstay of treatment for VHE, although more research is warranted to delineate the underlying risk factors for VHE and consolidate treatment modalities for this potentially life-threatening drug adverse effect.General hospital psychiatry 02/2012; 34(3):290-8. DOI:10.1016/j.genhosppsych.2011.12.009 · 2.90 Impact Factor