Clozapine ethnicity

These differences may become particularly germane if co-prescribing with some antipsychotics is undertaken. For example, in certain individuals, combinations of clozapine with benzodiazepines may lead to unexpected adverse events, including delirium and augmented respiratory depression (Jackson, Markowitz Brewer-ton, 1995 Grohmann et al, 1989). Presumably if there are additive or synergistic effects of ethnicity on clearance of one or both substances, adverse events may be enhanced. Similar interactions are theoretically possible with olanzapine, as adverse interactions have been described between olanzapine and benzodiazepines, at least in the elderly (Kryzhanovskaya etal, 2006). 

With respect to other ethnic groups, African Americans may have a differential sensitivity to weight gain on clozapine (de Leon etal, 2007). They may also require lower doses than Caucasians (Kelly et al, 2006) and inter-individual as well as ethnic responsiveness maybe partly explained by differences in dopamine receptor polymorphisms (Hwang et al, 2005). It is conceivable that side effects may also be differentially expressed based on pharmacodynamic differences resulting from polymorphisms in other receptor types (histaminergic, muscarinic, etc.). This area remains largely unexplored with respect to ethnic differences in antipsychotic side effects. 

Ng, C. H. et al. (2005). An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels. Int. Clin. Psychopharmacol., 20, 163-8. 

Corzo, D., et al., "The Major Histocompatibility Complex Region Marked by HSP and HSP70-2 Variant is Associated with Clozapine-induced Agranulocytosis in Two Different Ethnic Groups," Blood, 86, 3835-3840 (1995). 

Kohn, Y., Ebstein, R.P., Heresco-Levy, U., Shapira, B., Nemanov, L., Gritenko, I., Avnon, M., and Lerer, B. (1997) Dopamine D4 receptor gene polymorphisms relation to ethnicity., no association with schizophrenia and response to clozapine in Israeli subjects. Eur Neuropsychopharmacol, 7 39-43. 

Corzo D, el al. 1995. The major histocompatibility complex region marked by HSP70-1 and HSP70-2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups. Blood 86 3835-3840. 

There may be ethnic differences in susceptibility to ADRs. Corzo et al (1995) identified an association of alleles of the HLA-B and DR loci with increased risk of clozapine-induced agranulocytosis. Patients with abnormal pscudocholinesterase levels have prolonged apnea after receiving succi-nylcholine. Patients with low activity on N-acetyl transferase are more likely to develop lupus-like reactions to procainamide, hydralazine and isonia-zid (Peck et al 1993). 

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