The role of race and ethnicity in psychiatric diagnosis and treatment has received increased attention over the last 2 decades. In addition, recent studies conducted to determine the effects of psychotropic drugs among various racial and ethnic groups highlight the importance of considering race and ethnicity during psychopharmacologic interventions.

Information regarding differences in drug metabolism, effectiveness, and incidence of adverse effects provides opportunities for psychiatrists to adjust pharmacologic treatment to achieve optimal treatment outcomes while minimizing intolerable side effects. These differences have been explained by inconsistencies in access, stigma, fear of medicines, differing spiritual and cultural beliefs about mental illness, and general mistrust of the healthcare system by many racial and ethnic groups.

The articles in this supplement offer a significant contribution to the scientific foundation needed to minimize the patient and clinician factors contributing to the current disparities in mental health care. Recent data, such as those presented in this supplement, describe the role of ethnicity in the pharmacologic treatment of psychiatric disorders and offer hope for improved quality of care for ethnically diverse patient populations. The authors discuss differences in drug metabolism, the impact of these differences on development of various metabolic disorders, and how these differences may be useful in managing intolerable side effects and improving patient compliance and treatment outcome. The information included in these articles should assure that clinical decision making and prescribing practices include sensitivity to safety, tolerability, and dosing for an increasingly ethnically diverse population.

Atypical antipsychotics have become widely accepted as the first-line standard of care in the treatment of psychotic disorders, such as schizophrenia and bipolar disorder, which occur in ethnically and racially diverse patients. Accumulating data indicate that ethnicity factors may impact the efficacy and safety of atypical antipsychotics. Given the increasingly heterogeneous ethnic and racial composition of the United States, it is important for practicing clinicians to understand how race and ethnicity may influence the pharmacotherapeutic use of atypical antipsychotics.

The three articles in this supplement to CNS Spectrums, address how race and ethnicity may influence the efficacy, safety, tolerability, and dosing of atypical antipsychotics in today’s heterogeneous patient population.

L. DiAnne Bradford, PhD, reviews the most recent advances in ethnopharmacology and how gender, race, and ethnicity can influence, through metabolic biotransformation, the pharmacokinetic and pharmacodynamic properties of atypical antipsychotics. Dr. Bradford will also review how antipsychotic-related adverse events may be associated with the differences in oxidative enzyme activity across ethnic and racial groups and how these factors should be given careful consideration in the management of patients of different ethnic/genetic profiles.

David C. Henderson, MD, examines the emerging data that suggest metabolic differences among various racial and ethnic groups may predispose patients to serious medical complications, such as obesity, dyslipidemia, and diabetes mellitus. Dr. Henderson discusses the impact of these racial/ethnic metabolic differences when clinicians are prescribing atypical antipsychotics and also compares the risks of metabolic issues associated with specific agents within the class of atypical antipsychotics.

Since the risk of antipsychotic-induced adverse events is often related to plasma drug concentrations, factors that influence the metabolic transformation of these agents can substantially influence this risk. The cytochrome P450 (CYP) enzyme system, particularly CYP2D6, is very important for the metabolism of many typical and atypical antipsychotic agents. However, there is substantial ethnic/racial pharmacogenetic variability in the phenotypic (ie, metabolic rate) or genotypic (ie, presence of functional or nonfunctional alleles) expression of these enzyme systems. Caucasians have a bimodal distribution of CYP2D6 enzyme activity, with individuals classified either as extensive or poor metabolizers. In contrast, while there are few poor metabolizers among people of Asian descent, a substantial proportion of this population exhibits an intermediate rate of metabolism. African American populations also have a substantial number of intermediate metabolizers, and about the same number of poor metabolizers as Caucasians. Mexican Americans may have a slightly higher metabolic rate than other ethnic groups. Numerous studies have demonstrated that CYP2D6 metabolic status influences the clearance of conventional and atypical antipsychotics. African Americans and Asians, with CYP2D6 phenotypes or genotypes indicative of poor metabolizers, frequently exhibit significantly higher plasma drug concentrations and longer half-lives compared to extensive metabolizers. Importantly, this increased drug exposure is associated with an increased risk of extrapyramidal symptoms. Data on metabolic polymorphism of antipsychotics are lacking among African Americans. There are also some data suggesting that genetic polymorphism can influence the risk of antipsychotic-induced weight gain. These findings highlight the need to consider race/ethnicity when prescribing, dosing, and monitoring antipsychotic agents.

As the United States population continues to grow and diversify, physicians must be equipped to treat patients of different races and ethnicities. Current data suggest that certain ethnic minority groups may be predisposed to a variety of clinical conditions, including obesity, diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease. Furthermore, as physicians begin to turn more frequently to atypical antipsychotics in psychiatric illness, they face a growing concern regarding the development of metabolic side effects, especially in a US population that is gradually becoming more obese from a demographic standpoint. In addition, certain ethnic groups may be more susceptible to these metabolic effects. The metabolic side effects induced by the atypical antipsychotics vary greatly, with the newer agents generally displaying fewer and less severe side effects, indicating that the particular agent chosen is of critical importance. A risk/benefit assessment, taking into consideration any genetic predisposition, preexisting risk factors, and the side-effect profile of the specific agent, is paramount to the successful management of these patients. The ultimate goal is careful consideration of possible metabolic side effects in patients taking atypical antipsychotics, in order to avoid serious consequences.

Optimal treatment for patients with mental health illness depends upon accurate diagnosis, individualized treatment, patient adherence to effective agents, and an intact family support system. Healthcare system (eg, limited access to certain medications), provider (eg, bias and discrimination), and patient factors (eg, biologic and cultural) greatly influence the level of mental health care given, especially to minority populations. Furthermore, limited data in African Americans, Hispanics, and Asians suggest that there are racial, ethnic, and cultural variations in responsiveness to antipsychotic medications, as well as potential differences in the types, rates, and severity of adverse events. Non-Caucasian patients tend to receive older, less-expensive agents, sometimes at higher doses (African Americans, leading to potentially intolerable side effects and early withdrawal of therapy or a less than optimal therapeutic response, respectively. Differences in response may have a biologic, pharmacokinetic, or pharmacodynamic basis and may also be influenced by lifestyle factors (eg, diet, smoking). Variations in dopamine receptor occupancy and cytochrome P450 polymorphism may explain some racial/ethnic differences in antipsychotic effects and adverse-event profiles, suggesting that dosing may need to be individualized based on ethnicity. The newer atypical antipsychotics, while seemingly better tolerated compared with conventional antipsychotics, may not be totally devoid of bothersome side effects (eg, extrapyramidal side effects) in minorities. While further research is needed, recognition of potential interracial/ethnic pharmacogenetic differences may help minimize intolerable side effects and achieve optimal psychosis management.

The articles in this supplement demonstrate that ethnicity and ethnopharmacology have emerged as important considerations in the treatment of patients with mental illness. Patients from ethnically diverse backgrounds often demonstrate varying levels of response and tolerability to drugs such as atypical antipsychotics. In part, this response may be due to the particular agent itself, yet metabolic differences between populations may also impact these varied effects. Specific isoforms of the cytochrome P450 enzyme system can dictate the rate at which patients metabolize certain medications, thus genotypic variability among these enzymes predicts the phenotypic response or metabolic rate. For example, patients from certain ethnic groups such as Caucasians and Hispanics tend to be extensive metabolizers, while African Americans and Asians tend to be slower metabolizers.

Total dose and resulting plasma drug levels are closely related to adverse effects. Thus, patients exhibiting slow or poor oxidative enzyme activity may face increased drug exposure and potentially higher rates of adverse events. The undesirable antipsychotic-induced side effects include metabolic issues such as weight gain, insulin resistance, and dyslipidemia. Certain ethnic groups are at a higher risk for developing these metabolic problems. Side effects such as extrapyramidal symptoms and tardive dyskinesia, which have traditionally been attributed to conventional antipsychotics, may occur with atypicals although much less frequently. Movement disorders caused by the use of an atypical antipsychotic become particularly apparent when plasma drug levels are high. Patients with a slow metabolism will be exposed to high plasma drug levels, even on standard dosages of an atypical antipsychotic.

Therefore, given a genetic predisposition and the potential for metabolic side effects with atypical antipsychotics, a careful risk/benefit assessment is crucial for the successful management of patients with mental illness.

Other patient factors as well as clinician factors can influence the response and tolerability of treatment. Provider biases can affect access to certain medications, while misconceptions about how to treat certain ethnic groups can affect the initial choice of medication and dosage. Ultimately, sensitivity and an awareness of pharmacologic issues as they relate to an expanding and ethnically diverse population must become a high priority for clinicians treating patients with atypical antipsychotics. Side effects of these medications can be minimized with vigilance and a thorough understanding of the risks and benefits.

Continued research is necessary to further understand the field of ethnopharmacology and to lead psychiatry into the future of individualized, metabolically directed therapies.