‘Drop attacks’ in this context were thought to be atonic seizures, which are the result of sudden loss of muscle tone [Berman et al. 1992] or flexion tonic seizures [Antelo et al. 1994] resulting from muscle contraction rather

than loss of muscle tone. Eight cases of clozapine-induced stuttering have been reported [Hallahan et al. 2007; Lyall et al. 2007; Begum, 2005; Duggal et al. 2002; Supprian et al. 1999; Thomas et al. 1994]. These occurred at doses ranging between 125 mg [Thomas et al. 1994] and 700 mg [Supprian et al. 1999] with two authors Belnacasan (VX-765) suggesting a dose-dependent relationship Inhibitors,research,lifescience,medical [Hallahan et al. 2007; Thomas et al. 1994]. Three case reports associated clozapine-induced stuttering with seizure activity [Begum, 2005; Duggal et al. 2002; Supprian et al. 1999] and this view is supported by four cases where the use of http://www.selleckchem.com/products/Calcitriol-(Rocaltrol).html valproate Inhibitors,research,lifescience,medical greatly improved speech difficulties [Lyall et al. 2007; Begum, 2005; Duggal et al. 2002; Supprian et al. 1999], including facial tics as reported by Begum. Three patients went on to have a generalized seizure [Hallahan et al. 2007; Duggal et al. 2002; Supprian et al. 1999]. Special Inhibitors,research,lifescience,medical cases: Cigarette smoking and Asian patients Cigarette smoking reduces clozapine plasma levels by up to 50% and higher doses may be required in smokers than in nonsmokers. Plasma level reduction

may be even greater in those receiving valproate [Taylor et al. 2009a]. Inhibitors,research,lifescience,medical Tobacco smoke contains polycyclic aromatic hydrocarbons that induce liver enzymes, in particular CYP1A2 which in turn increases the metabolism of

clozapine. This effect is particularly important when patients give up smoking; the enzyme activity lessens causing the clozapine plasma level to rise substantially, often requiring a reduction in dose. Nicotine replacement agents, however, have no effect on this process. Close monitoring of clozapine plasma levels is crucial, as seizures have occurred 8 weeks following smoking cessation in a clozapine responder [McCarthy, 1994]. The patient was also on fluoxetine, which can raise clozapine levels by 30–75% [Spina et al. 1998; Centorrino et Inhibitors,research,lifescience,medical al. 1994] however, the author observed seizure Cilengitide occurrence only after the smoking cessation. Seizures were reported in two Asian patients on low-dose (200 mg) clozapine: in one case a male Chinese patient discontinued low-dose benzodiazepine (lorazepam), and a seizure occurred 40 hours after the last lorazepam dose [Lane et al. 1999]. The authors hypothesized that stopping the lorazepam may have unmasked the underlying seizure potential from clozapine. In the second case [Ravasia and Dickson, 1998] a tonic—clonic seizure was observed in a female Vietnamese patient whose clozapine plasma level was 1076 μg/l preseizure. Considering the lack of more familiar risk factors, the authors suggested the patient may have been a slow metabolizer of clozapine, and that race may be a risk factor for seizures on clozapine.