Diazepam/olanzapine/valproate semisodium interaction
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Encephalopathy: case report A 36-year-old woman developed encephalopathy while receiving valproate semisodium, olanzapine and diazepam [routes not stated]. The woman, who was admitted with a manic episode, initially received diazepam 30 mg/day for agitation. Valproate semisodium 1000 mg/day was then added; however, her condition continued to deteriorate. On hospital day 4, valproate semisodium was increased to 1500 mg/day and olanzapine 10 mg/day was added. She subsequently became drowsy [duration of treatment to reaction onset not stated]. Despite withdrawal of diazepam, the woman gradually went into a coma the next morning. All drugs were then discontinued. Tests revealed a serum valproate concentration of 120 mg/L (therapeutic range 45–125 mg/L). Some hours later, her serum valproate concentration had decreased; however she remained in a deep, nonreactive coma. EEG revealed severe encephalopathy. She was transferred to an ICU and intubated. Twenty-four hours later, she had fully recovered. Within the next 48 hours, the woman restarted olanzapine. There were no further adverse effects. Twelve days after the encephalopathy, EEG was normal. She was discharged on olanzapine 20 mg/day. Author comment: "First, the psychotropic effects of these three drugs may be potentiated by their association and may induce deeper sedation. Second, [valproate semisodium], olanzapine, and diazepam . . . may have saturated the binding sites of plasma proteins and thus increased the free fraction of these drugs, especially for [valproate semisodium]." Trojak B, et al. Valproate-induced encephalopathy related to concurrent antimanic medications. Journal of Neuropsychiatry and Clinical Neurosciences 23: E22-E23, No. 1, 2011. Available from: URL: http://dx.doi.org/10.1176/ 803065196 appi.neuropsych.23.1.e22 - France
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Reactions 14 Jan 2012 No. 1384
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