Clozapine/caffeine/valproic acid interaction
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Decreased serum clozapine concentration in a heavy smoker: case report A 23-year-old man with disorganised schizophrenia experienced decreased serum clozapine concentrations during clozapine treatment; interactions with valproic acid, caffeine and nicotine may have been contributory factors. The man, who had a history of substance abuse, began carrying out auto-lesionist acts at 16 years of age. Over the next 5 years, he was treated with clozapine, amisulpride, haloperidol and benzodiazepines. In April 2010, he was hospitalised under mandatory psychiatric hold following a delusional auto-lesionist act. While in hospital, he received multiple drugs, including clozapine ≤900 mg/day and valproic acid 500 mg/day [routes not stated]. He also smoked 15-20 cigarettes and drank 6-7 cups of coffee on a daily basis. In June 2010, clozapine was replaced with risperidone due to lack of efficacy. His psychopathological status deteriorated, and he developed new episodes of selfinjurious behaviour. Despite treatment with the maximum indicated dosage of clozapine, no clinical improvement was seen. In October 2010, he was moved to a therapeutic community; his medications included clozapine 800 mg/day and valproic acid 500 mg/day. His serum concentration of clozapine was 168.03 ng/mL, considerably lower than the therapeutic threshold of 350 ng/mL [outcome not stated]. Author comment: "The patient met several factors increasing or decreasing clozapine plasma levels: he was male and young, he had an inappropriate diet, he daily smoked 15-20 cigarettes, he took valproic acid, and he daily drank six to seven cups of coffee." Bersani FS, et al. Factors affecting interindividual differences in clozapine response: A review and case report. Human Psychopharmacology: Clinical and Experimental 26: 177-187, No. 3, Apr 2011. Available from: URL: http:// 803060983 dx.doi.org/10.1002/hup.1191 - Italy
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Reactions 1 Oct 2011 No. 1371
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