Psychiatric Annals

Racial and Ethnic Issues Affect Treatment for Bipolar Disorder

William B Lawson, MD, PhD; Tony Strickland, PhD

Abstract

1. US Department of Health and Human Services. Mental Health: Culture, Race, and Ethnicity. A Supplement to Mental Health: A Report of the Surgeon General. Available at: http://www.surgeongeneral.gov/library/mentalhealth/cre/execsummary- 1 .html. Accessed November 25, 2003.

2. Miranda J, Lawson W, Escobar J; NIMH Affective Disorders Workgroup. Ethnic minorities, Ment Health Serv Res. 2002;4(4):23 1-237.

3. Wells KB, Miranda J, Bauer MS. et al. Overcoming barriers to reducing the burden of affective disorders. Biol Psychiatry. 2002;52(6):655-675.

4. Lawson WB. Racial and ethnic factors in psychiatric research. Hasp Community Psychiatry. 1986;37(1):50-54.

5. Flaskerud JH, Hu LT. Racial/ethnic identity and amount and type of psychiatric treatment. Am J Psychiatry. 1992;149(3):379-384.

6. Strickland TL, Ranganath V, Lin KM, et al. Psychopharmacologic considerations in the treatment of black American populations. Psychophartnacol Bull. l991;274):441-448.

7. Chung H, Mahler JC, Kakuma T. Racial differences in the treatment of psychiatric inpatients. Psychiatr Serv. 1995;46(6):586-591.

8. Segal SP, Bola J, Watson M. Race, quality of care, and antipsychotic prescribing practices in psychiatric emergency services. Psychiatr Serv. 1996;47(3):282-286.

9. Strakowski SM, Lonczak HS, Sax K, et al. The effects of race on diagnosis and disposition from a psychiatric emergency service. J Clin Psychiatry. 1995;56(3): 101-107.

10. Mukherjee S, Shukla S, Woodie J, Rosen AM, Olarte S. Misdiagnosis of schizophrenia in bipolar patients: a multi-ethnic comparison. Am J Psychiatry. 1983;140(12):1571-1574.

11. Ghaemi SN, Boiman EE1 Goodwin FK. Diagnosing bipolar disorder and the effects of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61(10):804-808.

12. Lovell D, Gagliardi GJ. Peterson PD. Recidivism and use of services among persons with mental illness after release from prison. Psychiatr Serv. 2002;53(10):1290-1296.

13. Walkup JT, Mc Alpine DD, Olfson M, et al. Patients with schizophrenia at risk for excessive antipsychotic dosing. J Clin Psychiatiy. 2000;61(5):344-348.

14. Bell CC, Mehta H. The misdiagnosis of black patients with mani-depressive illness. J Natl MedAssoc. I980;72(2):141-145.

15. Bell CC, Mehta H. Misdiagnosis of black patient with manic-depressive illness: second in a series. J Natl Med Assoc. 1981:73(2): 101-107.

16. Strakowski S. How to avoid ethnic bias when diagnosing schizophrenia. Curr Psychiatry. 2003;2:72-82.

17. Hirschfeld RM, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64(1):53-59.

18. Brown DR, Ahmed F, Gary LE, Milburn NG. Major depression in a community sample of Africaa Americans. Am J Psychiatry. 1995;152(3):373-378.

19. Sussman LK, Robins LN, Earls F. Treatmentseeking for depression by black and white Americans. Soc Sei Med. I987;24(3):I87196.

20. Neighbors HW. The distribution of psychiatric morbidity in black Americans: a review and suggestion for research. Camm Mental Health J. 1984;20(3): 169-181.

21. Copeland LA, Zeber JE, Valenstein M, Blow FC. Racial disparity in the use of atypical antipsychotic medications among veterans. Am J Psychiatry. 2003:160(10): 1817-1822

22. Opolka JL, Rascati KL, Brown CM, et al. Ethnic differences in use of antipsychotic medication among Texas Medicaid clines with schizophrenia. J Clin Psychiatry. 2003;64(6):635-639.

23. Melfi CA, Croghan TW, Hanna MP. Access to treatment for depression in a medicaid population. J Health Care Poor Underserved. 1999;10(2):201-215.

24. Melfi CA. Croghan TW, Hanna MP, Robinson RL. Racial variation in antidepressant treatment in a Medicaid population. J Clin Psychiatry. 20O0;61(1):16-21.

25. Olfson M, Marcus SC, Pincus HA, et al. Antidepressant prescribing practices of outpatient psychiatrists. Arch Gen Psychiatry. 1998;55(4):310-316.

26. Skaer TL, Selar DA. Robison LM, Galin RS. Trends in the rate of depressive illness and use of antidperessant pharmacotherapy by ethnicity/race: an assessment of office-based visits in the United States, 1992-1997. Clin Ther. 2000;22:1575-1589.

27. Blazer DG, Hybels CF. Simonsick EM1 HanIon JT Marked differences in antidepressant use by race in an elderly community sample: 1986-1996. Am J Psychiatry. 2000;157(7):1089-1094.…

The Surgeon General's Report on Mental Health, Culture, Race and Ethnicity provided a comprehensive review of diagnosis and treatment of ethnic minorities during a time of increasing national diversity, according to recent census data.1 The report documented that ethnic disparities in treatment availability still persist for many disorders. Bipolar affective disorder is no exception.

A recent review reported AfricanAmericans and Latinos are less likely to be treated and consistently receive suboptimal treatment when treatment is provided.2 There appears to be limited access to mental health services and to evidencebased, optimal treatment. Multiple studies have shown that African-Americans and other racial or ethnic minorities either are undertreated or are treated inappropriately.3,4 For example, ethnic minorities are less likely to receive psychotherapy.5 African-Americans are more likely to receive antipsychotic medication, depot medication, and higher doses of medication across diagnostic categories, perhaps leading to suboptimal response and poor compliance.6-8

These issues especially affect bipolar affective disorder.2,3 As noted in this issue, bipolar affective disorder is increasingly recognized as a spectrum of disorders that requires well skilled providers to adequately diagnose. Some studies have shown that the diagnosis may be missed 40% to 50% of the time, irrespective of ethnicity.9, 10 Moreover, treatment is complex and requires skilled clinicians, as polypharmacy is often required. We will discuss the implications of these concerns in this review.

LIMITED ACCESS TO TREATMENT DUE TO MISDIAGNOSIS

Bipolar affective disorder was thought to be rare among ethnic minorities, probably because of misdiagnosis and underdiagnosis. Despite improved diagnostic instruments, bipolar and other mood disorders continue to be under-recognized, especially for racial and ethnic minorities.9-11

Some individuals are never diagnosed and therefore never treated. They probably comprise a substantial percentage of the homeless and underemployed. Manies in particular are prone to inappropriate and dramatic, sometimes violent, behavior. It is probable that they comprise a significant percentage of the correctional population, which is disproportionately minority and increasingly recognized as the primary mental health provider in the United States.12

Misdiagnosis affects pharmacotherapy. For the past 2 decades, studies have shown that African-Americans with definitive symptoms of bipolar disorder were more likely to receive a diagnosis of schizophrenia and less likely to receive lithium therapy or other treatments for mood disorder. Recent studies continue to show that African-Americans with affective disorders are less likely to receive antimanic agents and more likely to receive antipsychotics.7,13-16 Patients on antipsychotics alone may be treated for acute symptoms of mania.

Most studies have focused on the misdiagnosis of bipolar I. Bipolar II, which requires major depression but hypomania rather then mania as its diagnostic criteria, is probably underdiagnosed as depression. This disorder is especially likely to be missed and may account for as much as 4% of the population.17 There is no data on ethnic minorities, but it is reasonable to assume that these patients are likely to be treated exclusively with antidepressants, although there is no treatment standard for this subgroup.10

DELAYED TREATMENT OR TREATMENT FROM NON-HEALTH PROFESSIONALS

Treatment-seeking behavior by ethnic minorities may have an important affect on treatment access and subsequent pharmacotherapy. For differing reasons, African-Americans, Latinos, and Asian-Americans often delay seeking treatment from standard mental health providers. African- Americans who are in distress or depressed often do not seek professional help, because of either lack of information or fear of hospitalization or involuntary commitment. When treatment is sought, it is usually after a delay. AsianAmericans also avoid treatment in the standard mental health system, often because of the stigma to the family.2,3,18,19

When treatment is sought, many times ethnic minorities may contact nonmental health professionals, including primary care providers, family members, friends, or the faith community.3-20 With the exception of primary care providers, help is being sought from individuals unfamiliar with pharmacotherapy. As previously noted, many individuals end up in the correctional system, where health treatment may be substandard or nonexistent.

OPTIMAL TREATMENT

Unlike other psychiatric disorders, polypharmacy is the rule rather than the exception in treating bipolar disorder. Mania and depression often occur in the same individuals, and both must be treated, often with different agents. Acute symptoms must be treated and maintenance treatment must be provided to prevent future exacerbations, also often with different agents. Consequently, the diagnostic issues and differing treatment demands may have special implications for racial and ethnic minorities. Many primary care providers or other generalists may not be as familiar with the complexity of treating this disorder, because it involves only a small percentage of their patient loads and easily can be confused with unipolar depression.10

Treatment compliance is often a major problem with bipolar disorder. Patients may have excellent functionality and may be asymptomatic between episodes. They frequently do not see the value of maintenance therapy. Poor compliance is probably even more common among ethnic minorities. Psychotherapeutic and rehabilitative support can improve compliance yet ethnic minorities are far more likely to be referred for medication alone and my not have access to rehabilitative or psychotherapy. The reasons for the lack of access are probably related to the limited access to mental health providers and the overdiagnosis of schizophrenia.3,16

Newer Medications

Antipsychotic medications and antidepressants continue to play key roles in the comprehensive treatment of bipolar disorder. Antipsychotics are often used to treat acute mania. Newer atypical, or second-generation, antipsychotics may offer additional benefits, including improved mood stabilization and less suicide risk. Suicide rates in bipolar disorder are the highest of any axis 1 disorder. Fewer extrapyramidal symptoms, which should improve compliance, and less tardive dyskinesia (more lilcely for affective disorder), are also benefits of newer medications.

Unfortunately, multiple studies show that African-Americans and Hispanics are less likely to have access to these medications. The reasons are complex but include cost. Many of these studies, however, included Medicaid patients, who should have similar incomes, or veterans, whose mental health costs are often covered.21,22

Antidepressant medication have been recognized to play a keep role in bipolar depression and mixed states. However the older tricyclic medications appear to convey a risk for manic exacerbation and rapid cycling.10 The newer specific serotonin reuptake inhibitors (SSRIs) and other third-generation antidepressants seem to be associated with less risk, yet these agents are also less available to ethnic minorities.23,27

PHARMACOKINETICS AND TOLERABILITY

Asians often are prescribed lower doses of psychotropic medications, including antipsychotics and antidepressants, and may have more side effects at standard doses. Pharmacokinetic differences have been found for first-generation antipsychotics and tricyclic antidepressants. Many of these agents are metabolized through the P450 microsomal enzyme system, where polymorphisms have been found for Asian populations that make them slow metabolizers. African-Americans also tend to be slow metabolizers of antipsychotics and antidepressants yet often are prescribed higher doses, increasing the risks of side effects and poor compliance.28-30

As noted, African-Americans often do not have the same access to newer agents such as atypical antipsychotics and selective serotonin reuptake inhibitors. Yet these newer agent are not metabolized as often through the CYP 2D6 systems, which tend to experience the most ethnic-related polymorphisms for psychotropic medications. These agents therefore show less ethnic polymorphism, which suggests a potential benefit for ethnic minorities.31

The already present risk of tardive dyskinesia associated with mood disorders is exacerbated in African-Americans taking first-generation antipsychotics. The risk is increased even further by the lack of availability of newer antipsychotic medications.32,33

Ethnic variability also has been found in antimanic medication. African Americans have been known to show a higher red blood cell to plasma lithium ratio than Caucasians,34,35 African-Americans also reported more side effects from lithium during a standardized interview. Moreover, side-effect ratings were directly related to the red blood cell to plasma lithium ratio. Other reports suggest an increased risk of other side effects with a high plasma to red blood cell ratio, such as lithium neuroleptic toxicity.34 It is not known if African-Americans require a lower clinical dose, but caution is warranted. It is premature to conclude that African-Americans should not receive lithium, especially considering evidence that lithium may provide better suicide protection compared with other antimanic agents.36

The development of newer treatments would especially benefit racial and ethnic minorities with bipolar disorder. Unfortunately, African Americans and other minorities often do not participate in clinical trials.4,37 A major reason for this is the lack of ethnic-minority selection for clinical-trial inclusion. However, many minorities refuse to participate. Widespread awareness of the Tuskegee study is a major reason African Americans refuse to volunteer for studies.38 This was a federally sponsored study initiated in the 30s in which African American men diagnosed with syphilis had treatment withheld without their knowledge. Only newspaper exposés in the 70s ended the study. As a result, research of any kind is viewed with suspicion, consequently those most in need of new treatments do no have them available.

SUMMARY

Racial and ethnic minorities with bipolar disorder may not have adequate access to treatment and services. Because ethnic minorities are often under-represented in most studies, additional research is clearly needed in order to better understand the barriers to access.3,4

This review suggests several ways to improve care, such as improving diagnostic accuracy and access to treatment and newer medications. Additional research is needed to address the risk and cost associated with newer treatments for ethnic minorities, as well as to explore the efficacy of each medication in various ethnic groups.

In addition, further research is needed on the development of novel agents that are better tolerated by AfricanAmericans and other ethnic minorities. Unfortunately, African- Americans are often under-represented in clinical trials or as investigators.

REFERENCES

1. US Department of Health and Human Services. Mental Health: Culture, Race, and Ethnicity. A Supplement to Mental Health: A Report of the Surgeon General. Available at: http://www.surgeongeneral.gov/library/mentalhealth/cre/execsummary- 1 .html. Accessed November 25, 2003.

2. Miranda J, Lawson W, Escobar J; NIMH Affective Disorders Workgroup. Ethnic minorities, Ment Health Serv Res. 2002;4(4):23 1-237.

3. Wells KB, Miranda J, Bauer MS. et al. Overcoming barriers to reducing the burden of affective disorders. Biol Psychiatry. 2002;52(6):655-675.

4. Lawson WB. Racial and ethnic factors in psychiatric research. Hasp Community Psychiatry. 1986;37(1):50-54.

5. Flaskerud JH, Hu LT. Racial/ethnic identity and amount and type of psychiatric treatment. Am J Psychiatry. 1992;149(3):379-384.

6. Strickland TL, Ranganath V, Lin KM, et al. Psychopharmacologic considerations in the treatment of black American populations. Psychophartnacol Bull. l991;274):441-448.

7. Chung H, Mahler JC, Kakuma T. Racial differences in the treatment of psychiatric inpatients. Psychiatr Serv. 1995;46(6):586-591.

8. Segal SP, Bola J, Watson M. Race, quality of care, and antipsychotic prescribing practices in psychiatric emergency services. Psychiatr Serv. 1996;47(3):282-286.

9. Strakowski SM, Lonczak HS, Sax K, et al. The effects of race on diagnosis and disposition from a psychiatric emergency service. J Clin Psychiatry. 1995;56(3): 101-107.

10. Mukherjee S, Shukla S, Woodie J, Rosen AM, Olarte S. Misdiagnosis of schizophrenia in bipolar patients: a multi-ethnic comparison. Am J Psychiatry. 1983;140(12):1571-1574.

11. Ghaemi SN, Boiman EE1 Goodwin FK. Diagnosing bipolar disorder and the effects of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61(10):804-808.

12. Lovell D, Gagliardi GJ. Peterson PD. Recidivism and use of services among persons with mental illness after release from prison. Psychiatr Serv. 2002;53(10):1290-1296.

13. Walkup JT, Mc Alpine DD, Olfson M, et al. Patients with schizophrenia at risk for excessive antipsychotic dosing. J Clin Psychiatiy. 2000;61(5):344-348.

14. Bell CC, Mehta H. The misdiagnosis of black patients with mani-depressive illness. J Natl MedAssoc. I980;72(2):141-145.

15. Bell CC, Mehta H. Misdiagnosis of black patient with manic-depressive illness: second in a series. J Natl Med Assoc. 1981:73(2): 101-107.

16. Strakowski S. How to avoid ethnic bias when diagnosing schizophrenia. Curr Psychiatry. 2003;2:72-82.

17. Hirschfeld RM, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64(1):53-59.

18. Brown DR, Ahmed F, Gary LE, Milburn NG. Major depression in a community sample of Africaa Americans. Am J Psychiatry. 1995;152(3):373-378.

19. Sussman LK, Robins LN, Earls F. Treatmentseeking for depression by black and white Americans. Soc Sei Med. I987;24(3):I87196.

20. Neighbors HW. The distribution of psychiatric morbidity in black Americans: a review and suggestion for research. Camm Mental Health J. 1984;20(3): 169-181.

21. Copeland LA, Zeber JE, Valenstein M, Blow FC. Racial disparity in the use of atypical antipsychotic medications among veterans. Am J Psychiatry. 2003:160(10): 1817-1822

22. Opolka JL, Rascati KL, Brown CM, et al. Ethnic differences in use of antipsychotic medication among Texas Medicaid clines with schizophrenia. J Clin Psychiatry. 2003;64(6):635-639.

23. Melfi CA, Croghan TW, Hanna MP. Access to treatment for depression in a medicaid population. J Health Care Poor Underserved. 1999;10(2):201-215.

24. Melfi CA. Croghan TW, Hanna MP, Robinson RL. Racial variation in antidepressant treatment in a Medicaid population. J Clin Psychiatry. 20O0;61(1):16-21.

25. Olfson M, Marcus SC, Pincus HA, et al. Antidepressant prescribing practices of outpatient psychiatrists. Arch Gen Psychiatry. 1998;55(4):310-316.

26. Skaer TL, Selar DA. Robison LM, Galin RS. Trends in the rate of depressive illness and use of antidperessant pharmacotherapy by ethnicity/race: an assessment of office-based visits in the United States, 1992-1997. Clin Ther. 2000;22:1575-1589.

27. Blazer DG, Hybels CF. Simonsick EM1 HanIon JT Marked differences in antidepressant use by race in an elderly community sample: 1986-1996. Am J Psychiatry. 2000;157(7):1089-1094.

28. Bradford LD, Kirlin WG. Polymorphism of CYP2D6 in Black populations: implications for psychopharmacology. Int J Neuropsychopharmcol. 1998:1(2):173-185.

29. Lin KM, Finder E. Neuroleptic dosage for Asians. Am J Psychiatry. 1983:140(4):490491.

30. Lin KM, Poland RE. Ethnicity, Culture, and Psychopharmacology. In: Bloom FE, Kupier DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York. NY: Raven Press; 1995.

31. Sathirakul K, Chan C, Teng L, et al. Olanzapine pharmacokinetics are similar in Chinese and Caucasian subjects. Br J Clin Pharmacol. 2003;56(2): 184- 187.

32. Morgenstern H. Glazer WM. Identifying risk factors for tardive dyskinesia among chronic outpatients maintained on neuroleptic medications: results of the Yale tardive dyskinesia study. Arch Gen Psychiatry. I993;50(9):723733.

33. Glazer WM, Morgenstern H, Doucette J. Race and tardive dyskinesia among outpatients at a CMHC. Hasp Comm Psychiatry. 1994;45(1):38-42.

34. Okpaku S, Frazer A, Mendels J. A pilot study of racial differences in erythrocyte lithium transport. Am J Psychiatry. 1980;137(1):120-121.

35. Strickland TL, Lin KM, Fu P, Anderson D. Zheng Y. Comparison of lithium ratio between African-American and Caucasian bipolar patients. Biol Psychiatry. 1995;37(5):325-330.

36. Goodwin FK, Fireman B, Simon GE, et al: Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA. 2003;290(11):1467-1473.

37. Svenson CK. Representation of American blacks in clinical trials of new drugs. JAMA. 1989;261:263-265.

38. Shavers VL, Lynch CF, Burmeister LF. Knowledge of the Tuskegee study and its impact on the willingness to participate in medical research studies. J Natl Med Assoc. 2000:92(12):563-5 72.

10.3928/0048-5713-20040101-06

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