2. Triple Whammy—HIV, Mental Disorders, African Americans
A combination of factors contributes to the underuse or inappropriate use of psychotropic medications among African Americans, including skepticism about the mental healthcare system and clinicians’ practices. [Lawson 1996] Examples of the latter include underdiagnosis and inadequate prescribing of medications for affective disorders and overdiagnosis of schizophrenia and overuse of antipsychotics, resulting in more adverse effects and less favorable outcomes. Another factor is the potential ethnic differences in pharmacokinetics, which may require different dosing strategies. Together, these factors may lead African Americans with mental health problems to first pursue nonprofessional treatments, to seek delayed diagnosis and treatment, to experience more about
Researchers have reported significant differences between African American and white attitudes toward the use of psychotropic medications, with African Americans being less willing to use them. Schnittker reported that African Americans’ skepticism about psychotropic medications may stem from particular beliefs about such drugs, rather than from general attitudes about healthcare services, concluding that beliefs about healthcare will continue to represent an important factor in African Americans and other ethnicities’ use of specific treatment modalities for mental health issues. [Schnittker 2003]
Against this background of attitudes and practices concerning mental healthcare are the possible concerns regarding genetic variations that influence patients’ response to medications. Ethnopsychopharmacology examines both potential differences between ethnic groups’ responses to psychotropic medications and the reasons for such differences, including genetic, biological, environmental, and psychosocial factors. Greater understanding of the polymorphisms in the hepatic cytochrome P (CYP)-450 enzyme systems that are responsible for metabolizing most psychotropic medications lies behind much of the research in this field. However, some of the findings of that are conflicting, leaving many issues without definitive answers.
Pharmacokinetics and Pharmacodynamics. Pharmacokinetics refers to how a drug is absorbed, distributed, metabolized, and excreted from the body, and it is controlled by specific isoenzymes in the CYP450 system whose action can vary among individuals. For example, the 2D6 isoenzyme metabolizes many tricyclic and serotonergic antidepressants and most antipsychotics.
Pharmacodynamics refers to the role of specific receptors in mediating a drug’s effects and is determined by such factors as age, genetics, and comorbid conditions. Individual differences in pharmacodynamics between individuals with the same blood level and clearance rate of a medication may result in experiencing more or fewer adverse events or occurrence of adverse events at a lower dose. Moreover, culturally determined attitudes regarding illness and healthcare may influence individual responses to psychotropic medications. For example, some cultures may regard illness as an unavoidable condition that cannot be relieved by medication, [Keitel 1996] and other cultures treat illnesses with a variety of modalities, eg, combining licensed drugs with herbal preparations. [Chien 1993] Clinicians need to be cognizant of such beliefs so as to design a recommended treatment plan to which an individual patient is likely to adhere.
An analysis by Risby reported that a mutation in as many as 33% of African Americans is associated with decreased 2D6 metabolic rate, leading to a greater risk of adverse events and toxicities.[Risby 1996] In addition, polymorphisms in the 2D19 isoenzyme—found in approximately 18% to 22% of African Americans—have been associated with reduced metabolization of some benzodiazepines. [Strickland 1997]
Together, the differences in the 2D6 and 2D19 isoenzyme metabolization rates of commonly prescribed psychotropic medications may mean that more African Americans vs whites are likely to experience slower metabolization—with the potential for more frequent occurrence of adverse events—when receiving antidepressant, anxiolytic, and antipsychotic medications.[Pi 2005] This suggests that clinicians may need to exercise greater caution and weigh additional individual factors in prescribing such drugs for African American patients. [Strickland 1997]
A more recent analysis by Lesser and colleagues comparing African American and white responses to treatment with the antidepressant citalopram somewhat contradicts yet refines this recommendation. [Lesser 2010] These investigators reported comparable rates of efficacy and adverse effects in both African American and white patients, with the cautionary remark that “availability of services, number and frequency of visits, access to medication, careful monitoring of symptoms with subsequent dose escalations, etc. rather than individual differences in response, are likely contributors to disparities in outcome.” That is, access to and quality of mental healthcare services and careful monitoring of treatment may be of greater importance to patient outcomes than differences in ethnic response patterns.