Skip to main content
SpringerLink
Log in

Ethnic Differences in the Risks of Adverse Reactions to Drugs Used in the Treatment of Psychoses and Depression

A Systematic Review and Meta-Analysis

  • Original Research Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Background: Factors such as age, sex and disease state alter a patient’s susceptibility to adverse drug reactions (ADRs). Ethnicity may also alter the risk of an ADR.

Objective: To review the evidence for ethnic differences in susceptibility to adverse reactions to drugs used to treat psychoses and depression.

Data sources: We searched MEDLINE (from 1951), EMBASE (from 1974), and PsycINFO (from 1950) to March 2006.

Study selection: Studies were included if there was a mention of ethnicity, ethnic or racial groups and a description of a procedure to investigate ADRs specifically or a description of ADRs that were a result of drugs in therapeutic use. Studies selected by any two reviewers were retained if they referred to drugs used in the treatment of psychoses and related disorders or antidepressant drugs. Of 124 studies describing ADRs to antipsychotics or antidepressants, 51 reported data from different ethnic groups.

Data extraction: Data were extracted independently from those studies selected for inclusion by two reviewers, using a standard data extraction form. Studies were assessed for bias in order to determine the quality of the study.

Data synthesis: In a pooled analysis of patients treated with antipsychotics, the relative risk (RR) of tardive dyskinesia in Black compared with White patients was 1.03 (95% CI 0.85, 1.24); the RR of extrapyramidal symptoms in East Asian compared with non-East Asian patients was 1.38 (95% CI 1.11, 1.72); the RR of hyperglycaemia in Black compared with non-Black patients was 1.55 (95% CI 0.95, 2.53); and the RR of diabetes mellitus in non-White compared with White patients was 1.35 (95% CI 0.95, 1.92). It was impossible to perform pooled analysis of data from studies investigating antidepressants due to insufficient data.

Conclusions: We found limited evidence of ethnic differences in the risk of ADRs. The clinical implications of these results remain unclear because of confounding factors. Further progress will require improved recruitment of patients from different ethnic groups and an established consensus on how to define ethnicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329(7456): 15–9

    Article  PubMed  Google Scholar 

  2. Aronson JK, Ferner RE. Joining the DoTS: new approach to classifying adverse drug reactions. BMJ 2003; 327(7425): 1222–5

    Article  PubMed  CAS  Google Scholar 

  3. Morley KI, Hall WD. Using pharmacogenetics and pharmacogenomics in the treatment of psychiatric disorders: some ethical and economic considerations. J Mol Med 2004; 82(1): 21–30

    Article  PubMed  Google Scholar 

  4. Jaquenoud SE, van der Velden JW, Rentsch K, et al. Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance. Drug Saf 2006; 29(9): 735–68

    Article  Google Scholar 

  5. McDowell SE, Coleman JJ, Ferner RE. Systematic review and meta-analysis of ethnic differences in risks of adverse reactions to drugs used in cardiovascular medicine. BMJ 2006; 332(7551): 1177–81

    Article  PubMed  CAS  Google Scholar 

  6. Xie HG, Kim RB, Wood AJ, et al. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol 2001; 41: 815–50

    Article  PubMed  CAS  Google Scholar 

  7. Bjornsson TD, Wagner JA, Donahue SR, et al. A review and assessment of potential sources of ethnic differences in drug responsiveness. J Clin Pharmacol 2003; 43(9): 943–67

    Article  PubMed  CAS  Google Scholar 

  8. Tate SK, Goldstein DB. Will tomorrow’s medicines work for everyone? Nat Genet 2004; 36 (11 Suppl.): 34–S42

    Article  Google Scholar 

  9. Jorde LB, Wooding SP. Genetic variation, classification and ‘race’. Nat Genet 2004; 36 (11 Suppl.): 28–S33

    Article  Google Scholar 

  10. Daar AS, Singer PA. Pharmacogenetics and geographical ancestry: implications for drug development and global health. Nat Rev Genet 2005; 6(3): 241–6

    Article  PubMed  CAS  Google Scholar 

  11. Schwartz RS. Racial profiling in medical research. N Engl J Med 2001; 344(18): 1392–3

    Article  PubMed  CAS  Google Scholar 

  12. Wilson JF, Weale ME, Smith AC, et al. Population genetic structure of variable drug response. Nat Genet 2001; 29(3): 265–9

    Article  PubMed  CAS  Google Scholar 

  13. Cooper RS, Kaufman JS, Ward R. Race and genomics. N Engl J Med 2003; 348(12): 1166–70

    Article  PubMed  Google Scholar 

  14. Risch N, Burchard E, Ziv E, et al. Categorization of humans in biomedical research: genes, race and disease. Genome Biol 2002; 3(7): 1–12

    Article  Google Scholar 

  15. McKenzie K, Samele C, Van Horn E, et al. Comparison of the outcome and treatment of psychosis in people of Caribbean origin living in the UK and British Whites: report from the UK700 trial. Br J Psychiatry 2001; 178: 160–5

    Article  PubMed  CAS  Google Scholar 

  16. Morgan C, Mallett R, Hutchinson G, et al. Pathways to care and ethnicity: 1, sample characteristics and compulsory admission-report from the AESOP study. Br J Psychiatry 2005; 186: 281–9

    Article  PubMed  CAS  Google Scholar 

  17. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33(1): 159–74

    Article  PubMed  CAS  Google Scholar 

  18. British National Formulary. No. 50, 50th edition. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2005

  19. Higgins J, Green S. Assessment of study quality. Cochrane handbook for systematic reviews of interventions 4.2.5. Chichester: The Cochrane Collaboration, 2005

    Google Scholar 

  20. Bhopal R. Glossary of terms relating to ethnicity and race: for reflection and debate. J Epidemiol Community Health 2004; 58(6): 441–5

    Article  PubMed  CAS  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557–60

    Article  PubMed  Google Scholar 

  22. Egger M, Smith GD, Phillips AN. Meta-analysis: principles and procedures. BMJ 1997; 315(7121): 1533–7

    Article  PubMed  CAS  Google Scholar 

  23. Review Manager (RevMan). Oxford: The Cochrane Collaboration, 2002

  24. Morgenstern H, Glazer WM, Gibowski LD, et al. Predictors of tardive dyskinesia: results of a cross-sectional study in an outpatient population. J Chronic Dis 1987; 40(4): 319–27

    Article  PubMed  CAS  Google Scholar 

  25. Sramek J, Roy S, Ahrens T, et al. Prevalence of tardive dyskinesia among three ethnic groups of chronic psychiatric patients. Hosp Community Psychiatry 1991; 42(6): 590–2

    PubMed  CAS  Google Scholar 

  26. Richardson MA, Reilly MA, Read LL, et al. Phenylalanine kinetics are associated with tardive dyskinesia in men but not in women. Psychopharmacology (Berl) 1999; 143(4): 347–57

    Article  CAS  Google Scholar 

  27. Morgenstern H, Glazer WM. Identifying risk factors for tardive dyskinesia among long-term outpatients maintained with neuroleptic medications: results of the Yale Tardive Dyskinesia Study. Arch Gen Psychiatry 1993; 50(9): 723–33

    Article  PubMed  CAS  Google Scholar 

  28. Van Os J, Fahy T, Jones P, et al. Tardive dyskinesia: who is at risk? Acta Psychiatr Scand 1997; 96(3): 206–16

    Article  PubMed  Google Scholar 

  29. Jeste DV, Caligiuri MP, Paulsen JS, et al. Risk of tardive dyskinesia in older patients: a prospective longitudinal study of 266 outpatients. Arch Gen Psychiatry 1995; 52(9): 756–65

    Article  PubMed  CAS  Google Scholar 

  30. Chakos MH, Alvir JM, Woerner MG, et al. Incidence and correlates of tardive dyskinesia in first episode of schizophrenia. Arch Gen Psychiatry 1996; 53(4): 313–9

    Article  PubMed  CAS  Google Scholar 

  31. Van Os J, Walsh E, Van Horn E, et al. Changes in negative symptoms and the risk of tardive dyskinesia: a longitudinal study. UK700 Group. Acta Psychiatr Scand 2000; 101(4): 300–6

    PubMed  Google Scholar 

  32. Oosthuizen PP, Emsley RA, Maritz JS, et al. Incidence of tardive dyskinesia in first-episode psychosis patients treated with low-dose haloperidol. J Clin Psychiatry 2003; 64(9): 1075–80

    Article  PubMed  CAS  Google Scholar 

  33. Chong SA, Mahendran R, Machin D, et al. Tardive dyskinesia among Chinese and Malay patients with schizophrenia. J Clin Psychopharmacol 2002; 22(1): 26–30

    Article  PubMed  Google Scholar 

  34. Bhatia T, Sabeeha MR, Shriharsh V, et al. Clinical and familial correlates of tardive dyskinesia in India and Israel. J Postgrad Med 2004; 50(3): 167–72

    PubMed  CAS  Google Scholar 

  35. Jann MW, Chang WH, Davis CM, et al. Haloperidol and reduced haloperidol plasma levels in Chinese vs. non-Chinese psychiatric patients. Psychiatry Res 1989; 30(1): 45–52

    Article  PubMed  CAS  Google Scholar 

  36. Binder RL, Levy R. Extrapyramidal reactions in Asians. Am J Psychiatry 1981; 138(9): 1243–4

    PubMed  CAS  Google Scholar 

  37. Lin KM, Finder E. Neuroleptic dosage for Asians. Am J Psychiatry 1983; 140(4): 490–1

    PubMed  CAS  Google Scholar 

  38. Sramek JJ, Sayles MA, Simpson GM. Neuroleptic dosage for Asians: a failure to replicate. Am J Psychiatry 1986; 143(4): 535–6

    PubMed  CAS  Google Scholar 

  39. Lin KM, Poland RE, Nuccio I, et al. A longitudinal assessment of haloperidol doses and serum concentrations in Asian and Caucasian schizophrenic patients. Am J Psychiatry 1989; 146(10): 1307–11

    PubMed  CAS  Google Scholar 

  40. Lindenmayer JP, Czobor P, Volavka J, et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry 2003; 160(2): 290–6

    Article  PubMed  Google Scholar 

  41. Sernyak MJ, Gulanski B, Rosenheck R. Undiagnosed hyperglycemia in patients treated with atypical antipsychotics. J Clin Psychiatry 2005; 66(11): 1463–7

    Article  PubMed  CAS  Google Scholar 

  42. Sernyak MJ, Gulanski B, Leslie DL, et al. Undiagnosed hyperglycemia in clozapine-treated patients with schizophrenia. J Clin Psychiatry 2003; 64(5): 605–8

    Article  PubMed  CAS  Google Scholar 

  43. Henderson DC, Nguyen DD, Copeland PM, et al. Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study. J Clin Psychiatry 2005; 66(9): 1116–21

    Article  PubMed  CAS  Google Scholar 

  44. Barner JC, Worchel J, Yang M. Frequency of new-onset diabetes mellitus and use of antipsychotic drugs among Central Texas veterans. Pharmacotherapy 2004; 24(11): 1529–38

    Article  PubMed  Google Scholar 

  45. Lamberti JS, Costea GO, Olson D, et al. Diabetes mellitus among outpatients receiving clozapine: prevalence and clinical-demographic correlates. J Clin Psychiatry 2005; 66(7): 900–6

    Article  PubMed  Google Scholar 

  46. Sumiyoshi T, Roy A, Anil AE, et al. A comparison of incidence of diabetes mellitus between atypical antipsychotic drugs: a survey for clozapine, risperidone, olanzapine, and quetiapine. J Clin Psychopharmacol 2004; 24(3): 345–8

    Article  PubMed  Google Scholar 

  47. Lamberti JS, Crilly JF, Maharaj K, et al. Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs. J Clin Psychiatry 2004; 65(5): 702–6

    Article  PubMed  Google Scholar 

  48. Correll CU, Frederickson AM, Kane JM, et al. Metabolic syndrome and the risk of coronary heart disease in 367 patients treated with second-generation antipsychotic drugs. J Clin Psychiatry 2006; 67(4): 575–83

    Article  PubMed  CAS  Google Scholar 

  49. Zipursky RB, Gu H, Green AI, et al. Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol. Br J Psychiatry 2005; 187: 537–43

    Article  PubMed  Google Scholar 

  50. Basson BR, Kinon BJ, Taylor CC, et al. Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone. J Clin Psychiatry 2001; 62(4): 231–8

    Article  PubMed  CAS  Google Scholar 

  51. Andersen SW, Clemow DB, Corya SA. Long-term weight gain in patients treated with open-label olanzapine in combination with fluoxetine for major depressive disorder. J Clin Psychiatry 2005; 66(11): 1468–76

    Article  PubMed  CAS  Google Scholar 

  52. Munro J, O’Sullivan D, Andrews C, et al. Active monitoring of 12,760 clozapine recipients in the UK and Ireland: beyond pharmacovigilance. Br J Psychiatry 1999; 175: 576–80

    Article  PubMed  CAS  Google Scholar 

  53. Meged S, Stein D, Sitrota P, et al. Human leukocyte antigen typing, response to neuroleptics, and clozapine-induced agranulocytosis in Jewish Israeli schizophrenic patients. Int Clin Psychopharmacol 1999; 14(5): 305–12

    PubMed  CAS  Google Scholar 

  54. Lieberman JA, Yunis J, Egea E, et al. HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Arch Gen Psychiatry 1990; 47(10): 945–8

    Article  PubMed  CAS  Google Scholar 

  55. Fleck DE, Keck Jr PE, Corey KB, et al. Factors associated with medication adherence in African American and white patients with bipolar disorder. J Clin Psychiatry 2005; 66(5): 646–52

    Article  PubMed  Google Scholar 

  56. Ciliberto N, Bossie CA, Urioste R, et al. Lack of impact of race on the efficacy and safety of long-acting risperidone versus placebo in patients with schizophrenia or schizoaffective disorder. Int Clin Psychopharmacol 2005; 20(4): 207–12

    Article  PubMed  Google Scholar 

  57. Raskin A, Crook TH. Antidepressants in black and white inpatients: differential response to a controlled trial of chlorpromazine and imipramine. Arch Gen Psychiatry 1975; 32(5): 643–9

    Article  PubMed  CAS  Google Scholar 

  58. Matsuda KT, Cho MC, Lin KM, et al. Clozapine dosage, serum levels, efficacy, and side-effect profiles: a comparison of Korean-American and Caucasian patients. Psychopharmacol Bull 1996; 32(2): 253–7

    PubMed  CAS  Google Scholar 

  59. Ng CH, Chong SA, Lambert T, et al. An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels. Int Clin Psychopharmacol 2005; 20(3): 163–8

    Article  PubMed  Google Scholar 

  60. Moeller FG, Chen YW, Steinberg JL, et al. Risk factors for clozapine discontinuation among 805 patients in the VA hospital system. Ann Clin Psychiatry 1995; 7(4): 167–73

    Article  PubMed  CAS  Google Scholar 

  61. Strickland TL, Lin KM, Fu P, et al. Comparison of lithium ratio between African-American and Caucasian bipolar patients. Biol Psychiatry 1995; 37(5): 325–30

    Article  PubMed  CAS  Google Scholar 

  62. Marcos LR, Cancro R. Pharmacotherapy of Hispanic depressed patients: clinical observations. Am J Psychother 1982; 36(4): 505–12

    PubMed  CAS  Google Scholar 

  63. Sleath B, Rubin RH, Wurst K. The influence of Hispanic ethnicity on patients’ expression of complaints about and problems with adherence to antidepressant therapy. Clin Ther 2003; 25(6): 1739–49

    Article  PubMed  Google Scholar 

  64. Currier MB, Molina G, Kato M. Citalopram treatment of major depressive disorder in Hispanic HIV and AIDS patients: a prospective study. Psychosomatics 2004; 45(3): 210–6

    Article  PubMed  CAS  Google Scholar 

  65. Wagner GJ, Maguen S, Rabkin JG. Ethnic differences in response to fluoxetine in a controlled trial with depressed HIV-positive patients. Psychiatr Serv 1998; 49(2): 239–40

    PubMed  CAS  Google Scholar 

  66. Alonso M, Val E, Rapaport MH. An open-label study of SSRI treatment in depressed hispanic and non-Hispanic women [letter]. J Clin Psychiatry 1997; 58(1): 31

    Article  PubMed  CAS  Google Scholar 

  67. Diaz E, Woods SW, Rosenheck RA. Effects of ethnicity on psychotropic medications adherence. Community Ment Health J 2005; 41(5): 521–37

    Article  PubMed  Google Scholar 

  68. Ayalon L, Arean PA, Alvidrez J. Adherence to antidepressant medications in black and Latino elderly patients. Am J Geriatr Psychiatry 2005; 13(7): 572–80

    PubMed  Google Scholar 

  69. Ng CH, Norman TR, Naing KO, et al. A comparative study of sertraline dosages, plasma concentrations, efficacy and adverse reactions in Chinese versus Caucasian patients. Int Clin Psychopharmacol 2006; 21(2): 87–92

    Article  Google Scholar 

  70. Allen JJ, Rack PH, Vaddadi KS. Differences in the effects of clomipramine on English and Asian volunteers: preliminary report on a pilot study. Postgrad Med J 1977; 53 Suppl. 4: 79–86

    PubMed  CAS  Google Scholar 

  71. Livingston RL, Zucker DK, Isenberg K, et al. Tricyclic antidepressants and delirium. J Clin Psychiatry 1983; 44(5): 173–6

    PubMed  CAS  Google Scholar 

  72. Clayton AH, Pradko JF, Croft HA, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002; 63(4): 357–66

    Article  PubMed  Google Scholar 

  73. Bailey RK, Mallinckrodt CH, Wohlreich MM, et al. Duloxetine in the treatment of major depressive disorder: comparisons of safety and efficacy. J Natl Med Assoc 2006; 98(3): 437–47

    PubMed  Google Scholar 

  74. Roy-Byrne PP, Perera P, Pitts CD, et al. Paroxetine response and tolerability among ethnic minority patients with mood or anxiety disorders: a pooled analysis. J Clin Psychiatry 2005; 66(10): 1228–33

    Article  PubMed  CAS  Google Scholar 

  75. Kumana CR, Lauder IJ, Chan M, et al. Differences in diazepam pharmacokinetics in Chinese and white Caucasians: relation to body lipid stores. Eur J Clin Pharmacol 1987; 32(2): 211–5

    Article  PubMed  CAS  Google Scholar 

  76. Lin KM, Poland RE, Lau JK, et al. Haloperidol and prolactin concentrations in Asians and Caucasians. J Clin Psychopharmacol 1988; 8(3): 195–201

    Article  PubMed  CAS  Google Scholar 

  77. Chang WH, Chen TY, Lee CF, et al. Low plasma reduced haloperidol/haloperidol ratios in Chinese patients. Biol Psychiatry 1987; 22(11): 1406–8

    Article  PubMed  CAS  Google Scholar 

  78. Nikelly AG. Does DSM-III-R diagnose depression in non-Western patients? Int J Soc Psychiatry 1988; 34(4): 316–20

    Article  PubMed  CAS  Google Scholar 

  79. Mumford DB. Detection of psychiatric disorders among Asian patients presenting with somatic symptoms. Br J Hosp Med 1992; 47(3): 202–4

    PubMed  CAS  Google Scholar 

  80. Kirmayer LJ, Young A. Culture and somatization: clinical, epidemiological, and ethnographic perspectives. Psychosom Med 1998; 60(4): 420–30

    PubMed  CAS  Google Scholar 

  81. Simon GE, VonKorff M, Piccinelli M, et al. An international study of the relation between somatic symptoms and depression. N Engl J Med 1999; 341(18): 1329–35

    Article  PubMed  CAS  Google Scholar 

  82. Ruiz P, Varner RV, Small DR, et al. Ethnic differences in the neuroleptic treatment of schizophrenia. Psychiatr Q 1999; 70(2): 163–72

    Article  PubMed  CAS  Google Scholar 

  83. Opolka JL, Rascati KL, Brown CM, et al. Ethnicity and prescription patterns for haloperidol, risperidone, and olanzapine. Psychiatr Serv 2004; 55(2): 151–6

    Article  PubMed  Google Scholar 

  84. National Center for Chronic Disease Prevention and Health Promotion. Age-adjusted prevalence of diagnosed diabetes per 100 population, by race/ethnicity and sex, United States, 1980–2005 [online]. Available from URL: http://www.cdc.gov/diabetes/statistics/prev/national/tableraceeth-sex.htm [Accessed 2006 Apr 11]

  85. The Information Centre. Health survey for England 2004: health of ethnic minorities. Leeds: The Information Centre, 2006

    Google Scholar 

  86. Shai I, Jiang R, Manson JE, et al. Ethnicity, obesity, and risk of type 2 diabetes in women: a 20-year follow-up study. Diabetes Care 2006; 29(7): 1585–90

    Article  PubMed  Google Scholar 

  87. International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication [online]. Available from URL: http://www.icmje.org/#prepare [Accessed 2006 Apr 11]

  88. Derry S, Kong LY, Aronson JK. Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials. BMC Med Res Methodol 2001; 1: 7

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Sarah E. McDowell was supported by the Antidote Trust Fund of the Sandwell and West Birmingham Hospitals NHS Trust. The funding source had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review or approval of the manuscript. The authors have no conflicts of interest directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Queen Elizabeth Psychiatric Hospital, Birmingham, UK

    Sara Ormerod

  2. West Midlands Centre for Adverse Drug Reactions, City Hospital, Dudley Road, Birmingham, B18 7QH, UK

    Sarah E. McDowell &  Robin E. Ferner

  3. Department of Clinical Pharmacology, University of Birmingham, Birmingham, UK

    Jamie J. Coleman &  Robin E. Ferner

Authors
  1. Sara Ormerod
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah E. McDowell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jamie J. Coleman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robin E. Ferner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robin E. Ferner.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ormerod, S., McDowell, S.E., Coleman, J.J. et al. Ethnic Differences in the Risks of Adverse Reactions to Drugs Used in the Treatment of Psychoses and Depression. Drug-Safety 31, 597–607 (2008). https://doi.org/10.2165/00002018-200831070-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200831070-00005

Keywords

Search

Navigation