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Pharmacopsychiatry 2004; 37(4): 175-179
DOI: 10.1055/s-2004-827174
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

High Dose Antipsychotic Use in Schizophrenia: Findings of the REAP (Research on East Asia Psychotropic Prescriptions) Study

K. Sim1 , A. Su1 , J. Y. Leong1 , K. Yip1 , M.-Y. Chong2 , S. Fujii3 , S. Yang2 , G. S. Ungvari4 , T. Si5 , E. K. Chung6 , H.-Y. Tsang2 , N. Shinfuku3 , E. H. Kua7 , C. H. Tan7
  • 1Institute of Mental Health/Woodbridge Hospital, Singapore
  • 2Kaohsiung Medical University, Kaohsiung, Taiwan
  • 3Kobe University, Kobe, Japan
  • 4Chinese University of Hong Kong, Hong Kong
  • 5Peking University, Beijing, China
  • 6Seoul National Hospital, Seoul, Korea
  • 7National University of Singapore, Singapore
Further Information

Publication History

Received: 12.2.2003 Revised: 9.5.2003

Accepted: 3.7.2003

Publication Date:
01 July 2004 (online)

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Background: High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equivalents milligrams of antipsychotic per day) in the management of patients with schizophrenia are not uncommon, but most reports are from western countries. Recent functional neuroimaging studies have found that the previous notion concerning the use of antipsychotic medication, especially in high doses, was unsupported and untenable. Methods: This international study examined the use of high dose antipsychotic medication and its clinical correlates in schizophrenia patients within six East Asian countries/territories. Results: Within the study group (n = 2399), 430 patients (17.9 %) were prescribed high dose antipsychotics. Antipsychotic use varied significantly between countries, with Japan, Korea, and Singapore using higher doses than the other countries. High dose antipsychotic use was associated with younger age in Japan (p < 0.001), longer duration of admission (p < 0.001), duration of illness (p < 0.001, particularly in Korea and Taiwan), positive psychotic symptoms (p < 0.001, particularly in Japan and Korea), and aggression (p < 0.05, particularly in Japan), and also with a higher likelihood of extrapyramidal and autonomic adverse effects (p < 0.05, particularly in China). Country, younger age, the presence of delusions and disorganized speech, polypharmacy, and receiving depot medication but not atypical antipsychotic drugs were important predictors of high antipsychotic use.
Conclusions: This survey revealed that high antipsychotic dosing is not an uncommon practice in East Asia. It behooves the prescribing clinicians to constantly reevaluate the rationale for such a practice.

References

  • 1 Adams C E, Fenton M K, Quraishi S, David A S. Systematic meta-review of depot antipsychotic drugs for people with schizophrenia.  Br J Psychiatry. 2001;  179 290-299
    CrossrefPubMedSearch in Google Scholar
  • 2 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed Washington DC; American Psychiatric Association 1994
    Search in Google Scholar
  • 3 American Psychiatric Association. Practice Guidelines for the Treatment of Patients with Schizophrenia. Washington, DC; American Psychiatric Press 1997
    Search in Google Scholar
  • 4 Baptista T, Kin N M, Beaulieu S, de Baptista E A. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives.  Pharmacopsychiatry. 2002;  35 205-219
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Baptista T, Lacruz A, Angeles F, Silvera R, de Mendoza S, Mendoza M T. et al . Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration.  Pharmacopsychiatry. 2001;  34 223-231
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Barnes T R, Curson D A. Long-term depot antipsychotics. A risk-benefit assessment.  Drug Saf. 1994;  10 464-479
    PubMedSearch in Google Scholar
  • 7 Bollini P, Pampallona S, Orza M J, Adams M E, Chalmers T C. Antipsychotic drugs: is more worse? A meta-analysis of the published randomized control trials.  Psychol Med. 1994;  24 307-316
    CrossrefPubMedSearch in Google Scholar
  • 8 Buchanan R W, Kreyenbuhl J, Zito J M, Lehman A. The schizophrenia PORT pharmacological treatment recommendations: conformance and implications for symptoms and functional outcome.  Schizophr Bull. 2002;  28 63-73
    PubMedSearch in Google Scholar
  • 9 Canales P L, Olsen J, Miller A L. Role of antipsychotic polypharmacotherapy in the treatment of schizophrenia.  CNS Drugs. 1999;  12 179-188
    PubMedSearch in Google Scholar
  • 10 Castle D, Morgan V, Jablensky A. Antipsychotic use in Australia: the patients’ perspective.  Aust N Z J Psychiatry. 2002;  36 633-641
    CrossrefPubMedSearch in Google Scholar
  • 11 Centorrino F, Eakin M, Bahk W M, Kelleher J P, Goren J, Salvatore P. et al . Inpatient antipsychotic drug use in 1998, 1993, and 1989.  Am J Psychiatry. 2002;  159 1932-1935
    CrossrefPubMedSearch in Google Scholar
  • 12 Chang I M. Anti-aging and health-promoting constituents derived from traditional oriental herbal remedies: information retrieval using the TradiMed 2000 DB.  Ann NY Acad Sci. 2000;  928 281-286
    PubMedSearch in Google Scholar
  • 13 Diaz F J, De Leon J. Excessive antipsychotic dosing in 2 U.S. State hospitals.  J Clin Psychiatry. 2002;  63 998-1003
    CrossrefPubMedSearch in Google Scholar
  • 14 Farde L, Nordstrom A L, Wiesel F A, Pauli S, Halldin C, Sedvall G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects.  Arch Gen Psychiatry. 1992;  49 538-544
    Search in Google Scholar
  • 15 Freudenreich O, Goff D C. Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current c ombinations.  Acta Psychiatr Scand. 2002;  106 323-330
    CrossrefPubMedSearch in Google Scholar
  • 16 Galletly C A. Antipsychotic drug doses in a schizophrenia inpatient unit.  Aust N Z J Psychiatry. 1992;  26 574-576
    PubMedSearch in Google Scholar
  • 17 Gerlach J. Depot neuroleptics in relapse prevention: advantages and disadvantages. Int Clin Psychopharmacol 1995 suppl 5: 17-20
    Search in Google Scholar
  • 18 Hamann J, Leucht S, Kissling W. Are the second-generation antipsychotics cost-effective? A critical review on the background of different health systems.  Pharmacopsychiatry. 2003;  36 18-26
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Hansen T E, Casey D E, Hoffman W F. Neuroleptic intolerance.  Schizophr Bull. 1997;  23 567-582
    PubMedSearch in Google Scholar
  • 20 Heinz A, Knable M B, Weinberger D R. Dopamine D2 receptor imaging and neuroleptic drug response.  J Clin Psychiatry. 1996;  57 (suppl 11) 84-88
    PubMedSearch in Google Scholar
  • 21 Hirsch S R, Barnes T R. Clinical use of high-dose neuroleptics.  Br J Psychiatry. 1994;  164 94-96
    PubMedSearch in Google Scholar
  • 22 Inagaki A, Inada T, Fujii Y, Yagi G. Equivalent doses of Psychotropics. Tokyo; Seiwa Shoten 1999
    Search in Google Scholar
  • 23 Ito C, Kubota Y, Sato M. A prospective survey on drug choice for prescriptions for admitted patients with schizophrenia.  Psychiatry Clin Neurosci. 1999;  53 (suppl) S35-40
    PubMedSearch in Google Scholar
  • 24 Kane J M. The use of higher-dose antipsychotic medication. Comment on the Royal College of Psychiatrists' consensus statement.  Br J Psychiatry. 1994;  164 431-432
    PubMedSearch in Google Scholar
  • 25 Kane J M, Aguglia E, Altamura A C, Ayuso Gutierrez J L, Brunello N, Fleischhacker W W. et al . Guidelines for depot antipsychotic treatment in schizophrenia. European Neuropsychopharmacology Consensus Conference in Siena, Italy.  Eur Neuropsychopharmacol. 1998;  8 55-66
    CrossrefPubMedSearch in Google Scholar
  • 26 Leblanc G, Cormier H J, Vaillancourt S, Gagne M A, Gingras C. Who are the patients treated in an outpatient clinic with high dosage neuroleptics?.  Can J Psychiatry. 1990;  35 12-24
    PubMedSearch in Google Scholar
  • 27 Lehman A F, Steinwachs D M. Patterns of usual care for schizophrenia: initial results from the Schizophrenia Patient Outcomes Research Team (PORT) Client Survey.  Schizophr Bull. 1998;  24 11-20
    PubMedSearch in Google Scholar
  • 28 Lehman A F, Steinwachs D M. Translating research into practice: the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations.  Schizophr Bull. 1998;  24 1-10
    PubMedSearch in Google Scholar
  • 29 McEvoy J, Haughty G, Steingard S. Optimal dose of neuroleptic in acute schizophrenia: a controlled study of the neuroleptic threshold and higher haloperidol dose.  Arch Gen Psychiatry. 1991;  48 739-745
    CrossrefPubMedSearch in Google Scholar
  • 30 Mossman D. A decision analysis approach to neuroleptic dosing: insights from a mathematical model.  J Clin Psychiatry. 1997;  58 66-73
    PubMedSearch in Google Scholar
  • 31 Patel M X, Nikolaou V, David A S. Psychiatrists' attitudes to maintenance medication for patients with schizophrenia.  Psychol Med. 2003;  33 83-89
    CrossrefPubMedSearch in Google Scholar
  • 32 Stahl S M. Antipsychotic polypharmacy, part 2: tips on use and misuse.  J Clin Psychiatry. 1999;  60 506-507
    PubMedSearch in Google Scholar
  • 33 Stahl S M. Antipsychotic polypharmacy: squandering precious resources?.  J Clin Psychiatry. 2002;  63 93-94
    CrossrefPubMedSearch in Google Scholar
  • 34 Tavcar R, Dernovsek M Z, Zvan V. Choosing antipsychotic maintenance therapy - a naturalistic study.  Pharmacopsychiatry. 2000;  33 66-71
    Thieme ConnectPubMedSearch in Google Scholar
  • 35 Walburn J, Gray R, Gournay K, Quraishi S, David A S. Systematic review of patient and nurse attitudes to depot antipsychotic medication.  Br J Psychiatry. 2001;  179 300-307
    CrossrefPubMedSearch in Google Scholar
  • 36 Walkup J T, McAlpine D D, Olfson M, Labay L E, Boyer C, Hansell S. Patients with schizophrenia at risk for excessive antipsychotic dosing.  J Clin Psychiatry. 2000;  61 344-348
    CrossrefPubMedSearch in Google Scholar
  • 37 Whitworth A B, Fleischhacker W W. Adverse effects of antipsychotic drugs. Int Clin Psychopharmacol 1995 suppl 5: 21-27
    Search in Google Scholar
  • 38 World Health Organization. International Statistical Classification of Diseases and Related Health Problems. 10 rev Geneva; World Health Organization 1992
    Search in Google Scholar

Dr Kang Sim, MBBS (Melbourne), M. Med. (Psychiatry)

Woodbridge Hospital/Institute of Mental Health

10 Buangkok View

Singapore 539747

Phone: +65 6385 0411

Fax: +65 63892963

Email: kang_sim@imh.com.sg