Metabolic syndrome clozapine

As well as their effects on the brain, neuroleptics commonly produce other potentially lethal effects. They are all toxic to the heart, inducing conduction defects and arrhythmias. Olanzapine and clozapine also interfere with normal metabolism, causing what is known as metabolic syndrome. This syndrome has only recently been described and is defined as the occurrence of obesity, diabetes, hypertension and dyslipidaemia6 (Shirzadi Ghaemi 2006). The underlying cause of the syndrome is thought to be resistance to insulin. All these effects... 

A review of the literature (1975-2011) on metabolic syndrome reported a prevalence of 14.7-69.3% in non-Euro-American societies [67" ]. Olanzapine was associated with the highest incidence of metabolic syndrome while clozapine was associated with the highest prevalence. 

Susceptibility factors A study of tumour necrosis factor-alpha (TNF-a) in 99 patients with bipolar depression found that treatment with olanzapine, quetiapine, risperidone, paliperidone or clozapine was associated with significantly greater TNF-a and a higher likelihood of metabolic syndrome [74FI TNF-a was greater in those with metabolic syndrome and there was a significant effect on the indirect relationship between antipsychotic treatment and elevated waist circumference. 

Metabolism A functional polymorphism (Val66Met) of the brain-derived neurotrophic factor gene was found to be associated with clozapine-induced metabolic syndrome (significantly with fasting glucose levels) in males but not in females [121 ]. The increase in triglyceride levels with clozapine has been shown to be strongly predictive of clinical improvemenf [122 ]. 

Zhang Y, Chen M, Wu Z, Chen J, Yu S, Fang Y, et al. Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome preliminary results. PLoS One 2013 8(8) e72652. 

ARIPIPRAZOLE, HALOPERIDOL, CLOZAPINE, PIMOZIDE, RISPERIDONE, SERTINDOLE PROTEASE INHIBITORS Possibly T levels of antipsychotic Inhibition of CYP3A4- and/or CYP2D6-mediated metabolism Avoid co-administration of clozapine with ritonavir, and pimozide or sertindole with protease inhibitors. Use other antipsychotics with caution as 1 dose may be required with risperidone, watch closely for extrapyramidal side-effects and neuroepileptic malignant syndrome... 

Given concurrently with TCAs they may cause serious adverse effects. Fluvoxamine may raise levels of caffeine and theophylline, and fluoxetine can interfere with the metabolism of clozapine, cyclosporin, and tefenadine (18, 46). SSWs should never be given with MAO inhibitors because a fatal "serotonin syndrome" has been reported with fluoxetine in this combination (18). 

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