Racial/Ethnic Differences in the Pharmacokinetics of Antipsychotics: Focusing on East Asians

Abstract

Empirical clinical studies have suggested that East Asian patients may require lower dosages of psychotropic drugs, such as antipsychotics, lithium, and antidepressants, than non-Asians. Both the pharmacokinetic and pharmacodynamic properties of a drug can affect the clinical response of an illness. The levels of antipsychotics used for the treatment of schizophrenia may affect patient clinical responses; several factors can affect these levels, including patient medication adherence, body weight (BW) or body mass index, smoking habits, and sex. The cytochrome P450 (CYP) system is a major factor affecting the blood levels of antipsychotics because many antipsychotics are metabolized by this system. There were notable genetic differences between people of different races. In this study, we determined the racial or ethnic differences in the metabolic patterns of some selected antipsychotics by reviewing therapeutic drug monitoring studies in East Asian populations. The plasma concentrations of haloperidol, clozapine, quetiapine, aripiprazole, and lurasidone, which are metabolized by specific CYP enzymes, were determined to be higher, under the same daily dose, in East Asian populations than in Western populations.

Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

“…Unfortunately, biological diversity has not received enough attention in psychopharmacology practice, in general, and in patients of East Asian ancestry, specifically. Supplementary Table 14 (in the online-only Data Supplement) uses as examples four other psychiatric drugs (diazepam, 52,[180][181][182][183][184] carbamazepine, [185][186][187] olanzapine, 21,25,131,157,188 and haloperidol 24,61,64,[189][190][191] ) in which paying attention to East Asian ancestry may be important. The literature provides reasonable information concerning lower diazepam dosing in East Asians and for genotyping human leukocyte antigen-B*15:02 before starting carbamazepine in East Asian countries, except Japan.…”

“…The literature provides reasonable information concerning lower diazepam dosing in East Asians and for genotyping human leukocyte antigen-B*15:02 before starting carbamazepine in East Asian countries, except Japan. 185,186 On the other hand, it is likely that patients of East Asian ancestry may need lower doses of olanzapine 131 and haloperidol 191 and this appears to have been ignored by Western textbooks and articles.…”

Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta‐analysis

“…For example, the risk of extrapyramidal side effects increases dose‐dependently 11 . Second, empirical clinical studies suggest that East Asian patients may require lower dosages of psychotropic drugs, such as antipsychotics, lithium, and antidepressants, than non‐Asians 12 . Racial and ethnic groups differ genetically in the activity of cytochrome P450, which participates in the metabolism of many drugs 12 .…”

“…Second, empirical clinical studies suggest that East Asian patients may require lower dosages of psychotropic drugs, such as antipsychotics, lithium, and antidepressants, than non‐Asians 12 . Racial and ethnic groups differ genetically in the activity of cytochrome P450, which participates in the metabolism of many drugs 12 . Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of more than 20% of clinically prescribed drugs, including such as BRE and ARI 13 .…”

“…Because the CYP2D6 gene is highly polymorphic, individuals exhibit varying degrees of CYP2D6 enzyme activity, which could affect the safety and efficacy of drugs cleared and/or activated by CYP2D6 14 . A recent pharmacokinetic study reported that the plasma concentrations of some antipsychotics, including BRE, metabolized by specific CYP enzymes, might be higher with the same daily dose in East Asian populations than in Western populations 12 . A Japanese study has shown BRE1 to be effective in people with AR‐MDD 9 ; however, an international study with predominantly Caucasian participants did not 15 .…”