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Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians

By Adriana Foster, Zixuan Wang, Manzoor Usman, Edna Stirewalt and Peter Buckley

Abstract

There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders

Topics: Case Report
Publisher: Dove Medical Press
OAI identifier: oai:pubmedcentral.nih.gov:2656342
Provided by: PubMed Central
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    Citations

    1. (2004). A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation. Current Medicinal Chemistry,
    2. (2000). A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia. Mol Psychiatry,
    3. (2006). A functional variant of the dopamine D3 receptor is associated with risk and age at onset of essential tremor.
    4. (1976). Abnormal involuntary movement scale. In: ECDEU assessment manual for psychopharmacology.
    5. (2002). Abnormal movements and tardive dyskinesia in smokers and nonsmokers with schizophrenia genotyped for cytochrome P450 2D6.
    6. and their association with tardive dyskinesia in severe mental illness.
    7. (2002). Antipsychotic combination therapy in schizophrenia: A review of effi cacy and risks of current combinations.
    8. (2004). Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder.
    9. (2000). Association between cytochrome P4502D6 (CYP2D6) genotype, antipsychotic exposure, and abnormal involuntary movement scale (AIMS) score. Psychiatr Genet,
    10. (2001). Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry,
    11. (2004). Association in Japanese patients between neuroleptic malignant syndrome and functional polymorphisms of the dopamine D2 receptor gene. Molecular Psychiatry,
    12. (2000). Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: a generalization of Steen’s study on DRD3 and tardive dyskinesia.
    13. (1999). Association of the MscI polymorphism of the dopamine D3 receptor gene with tardive dyskinesia in schizophrenia.
    14. (2001). Association of the Taq1 polymorphism of the dopamine D2 receptor gene with predisposition to neuroleptic malignant syndrome.
    15. (2006). Association study of tardive dyskinesia and twelve DRD2 polymorphisms in schizophrenia patients.
    16. (2007). Challenges for corporate ethics in marketing genetic tests. Journal of Business Ethics advance online publication accessed 7/12/07 http://www.springerlink.com/content/ g6w320149833347h/?p=90f320134a9f4804b5bca7f6d3c3f60b&pi=0
    17. (1992). Clinical assessment of the extrapyramidal side effects of antipsychotic drugs.
    18. (2006). Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for
    19. (2006). Clinical implications of CYP2D6 genetic polymorphism during treatment with antipsychotic drugs. Current Drug Targets,
    20. (2005). Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism.
    21. (2005). Combined analysis of 635 patients confi rms an age related association of serotonin 2A receptor gene with tardive dyskinesia and specifi city for non-orofacial subtype.
    22. (2002). CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants.
    23. (1997). Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences.
    24. (2002). Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Clinical Pharmacokinetics,
    25. (2006). Diabetes risk associated with use of olanzapine, quetiapine and risperidone in veterans health administration patients with schizophrenia.
    26. (2001). Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics?
    27. (2001). Dopamine D3 receptor gene and tardive dyskinesia in Chinese schizophrenic patients.
    28. (2000). Dopamine D3 receptor variant and tardive dyskinesia. Eur Arch Psychiatry Clin Neurosci,
    29. (1997). Dopamine D3-receptor gene variant and susceptibility to tardive dyskinesia in schizophrenic patients. Mol Psychiatry,
    30. (2005). Drug metabolism and variability among patients in drug response.
    31. (1995). Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors.
    32. (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.
    33. (2000). Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness.
    34. (2007). Genetic Information Nondiscrimination Act of 2007, GovTrack.us (database of federal legislation).
    35. (1998). Genetic polymorphism for drug metabolism (CYP2D6) and tardive dyskinesia in schizophrenia. Schizophr Res,
    36. (2006). Genetic susceptibility to tardive dyskinesia among schizophrenia subjects: IV role of dopaminergic pathway gene polymorphisms. Pharmacogenetics and Genomics,
    37. (2005). Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects:
    38. (2006). Genetics of antipsychotic treatment emergent weight gain in schizophrenia.
    39. (2005). Genotype A1/A2 associated with neuroleptic malignant syndrome. Bipolar Disorders,
    40. (1999). Genotypic association between the dopamine D3 receptor and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry,
    41. (2006). Haloperidol versus placebo for schizophrenia. Cochrane Database of Systematic Reviews,
    42. (2006). Hyperlipidemia following treatment with antipsychotic medications.
    43. (2006). Imaging genomics and response to treatment with antipsychotics in schizophrenia.
    44. (2003). Impaired fasting glucose tolerance in fi rst-episode, drug-naive patients with schizophrenia.
    45. (2002). Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use.
    46. (2001). Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia.
    47. (2001). Lack of association between serotonin-2A receptor gene (HTR2A) polymorphisms and tardive dyskinesia in schizophrenia. Mol Psychiatry,
    48. (2007). Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia.
    49. (2007). Mapping translational research in personalized therapeutics.
    50. (2006). Medical risk in patients with bipolar disorder and schizophrenia.
    51. (2006). National Trends in the outpatient treatment of children and adolescents with antipsychotic drugs.
    52. (2001). No relationship between −141C Ins/ Del polymorphism in the promoter region of dopamine D2 receptor and extrapyramidal adverse effects of selective dopamine D2 antagonists in schizophrenic patients: a preliminary study. Psychiatry Research,
    53. (2003). Outpatient use of major antipsychotic drugs in ambulatory care settings, Medgenmed [computer fi le].
    54. (2004). Pathophysiology of antipsychotic drug-induced movement disorders.
    55. (2005). Pharmacogenetic studies of response to risperidone and other newer atypical antipsychotics.
    56. (2004). Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Molecular Psychiatry,
    57. (2006). Pharmacogenetics of antipsychotic therapy: pivotal research issues and the prospects for clinical implementation.
    58. (2004). Pharmacogenetics of cytochrome P450 and its applications in drug therapy, the past, present and future.
    59. (2004). Pharmacogenetics of psychotropic drug response.
    60. (2002). Pharmacogenetics of tardive dyskinesia. Combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism.
    61. (2005). Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a fi rst-episode psychosis. Pharmacogenetics and Genomics,
    62. (2004). QTc interval, CYP2D6 and CYP2C9 genotypes and risperidone plasma concentrations.
    63. (2002). Relationship between adverse effects of antipsychotic treatment and dopamine D[sub2] receptor polymorphisms in patients with schizophrenia. Molecular Psychiatry,
    64. (2003). Relationship between functional dopamine D2 and D3 receptors gene polymorphism and neuroleptic malignant syndrome.
    65. (2001). Relationship between Taq1 A dopamine D2 receptor (DRD2) polymorphism and prolactin response to bromperidol.
    66. (2007). Risperdal® prescribing information [online].
    67. (2006). Role of CYP pharmacogenetics and drug-drug interactions in the effi cacy and safety of atypical and other antipsychotic agents.
    68. (1997). Search for a susceptibility locus to tardive dyskinesia. Hum Psychopharmacol Clin Exp,
    69. (2006). Side effects of atypical antipsychotics: extrapyramidal symptoms and the metabolic syndrome. Harvard Review of Psychiatry,
    70. (2001). Susceptibility to neurolepticinduced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor. Biol Psychiatry,
    71. (1998). Tardive dyskinesia and debrisoquine 4-hydroxylase (CYP2D6) genotype in Japanese schizophrenics. Schizophr Res,
    72. (2006). The amplichip CYP450 genotyping test-integrating a new clinical tool. Mol Diag Ther,
    73. (2006). The cardiovascular and respiratory health of people with schizophrenia. Acta Psychiatrica Scandinavica,
    74. (2005). The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation.
    75. (2005). The dosing of atypical antipsychotics.
    76. (2002). The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment. Clinical Pharmacology and Therapeutics,
    77. (2005). The role of 5-HT2C receptor in the pharmacogenetics of antipsychotic drug treatment.
    78. (2006). The SOHO (Schizophrenia Outpatient Health Outcome) study: implications for treatment of schizophrenia.
    79. (2004). Using pharmacogenetics and pharmacogenomics in the treatment of psychiatric disorders: some ethical and economic considerations.
    80. (2005). Weight gain associated with the -759 C/T polymorphism of the 5HT2C receptor and olanzapine.

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