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

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
• 2 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed Washington DC; American Psychiatric Association 1994
• 3 American Psychiatric Association. Practice Guidelines for the Treatment of Patients with Schizophrenia. Washington, DC; American Psychiatric Press 1997
• 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
• 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
• 6 Barnes T R, Curson D A. Long-term depot antipsychotics. A risk-benefit assessment.  Drug Saf. 1994;  10 464-479
• 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
• 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
• 9 Canales P L, Olsen J, Miller A L. Role of antipsychotic polypharmacotherapy in the treatment of schizophrenia.  CNS Drugs. 1999;  12 179-188
• 10 Castle D, Morgan V, Jablensky A. Antipsychotic use in Australia: the patients’ perspective.  Aust N Z J Psychiatry. 2002;  36 633-641
• 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
• 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
• 13 Diaz F J, De Leon J. Excessive antipsychotic dosing in 2 U.S. State hospitals.  J Clin Psychiatry. 2002;  63 998-1003
• 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
• 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
• 16 Galletly C A. Antipsychotic drug doses in a schizophrenia inpatient unit.  Aust N Z J Psychiatry. 1992;  26 574-576
• 17 Gerlach J. Depot neuroleptics in relapse prevention: advantages and disadvantages. Int Clin Psychopharmacol 1995 suppl 5: 17-20
• 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
• 19 Hansen T E, Casey D E, Hoffman W F. Neuroleptic intolerance.  Schizophr Bull. 1997;  23 567-582
• 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
• 21 Hirsch S R, Barnes T R. Clinical use of high-dose neuroleptics.  Br J Psychiatry. 1994;  164 94-96
• 22 Inagaki A, Inada T, Fujii Y, Yagi G. Equivalent doses of Psychotropics. Tokyo; Seiwa Shoten 1999
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 30 Mossman D. A decision analysis approach to neuroleptic dosing: insights from a mathematical model.  J Clin Psychiatry. 1997;  58 66-73
• 31 Patel M X, Nikolaou V, David A S. Psychiatrists' attitudes to maintenance medication for patients with schizophrenia.  Psychol Med. 2003;  33 83-89
• 32 Stahl S M. Antipsychotic polypharmacy, part 2: tips on use and misuse.  J Clin Psychiatry. 1999;  60 506-507
• 33 Stahl S M. Antipsychotic polypharmacy: squandering precious resources?.  J Clin Psychiatry. 2002;  63 93-94
• 34 Tavcar R, Dernovsek M Z, Zvan V. Choosing antipsychotic maintenance therapy - a naturalistic study.  Pharmacopsychiatry. 2000;  33 66-71
• 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
• 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
• 37 Whitworth A B, Fleischhacker W W. Adverse effects of antipsychotic drugs. Int Clin Psychopharmacol 1995 suppl 5: 21-27
• 38 World Health Organization. International Statistical Classification of Diseases and Related Health Problems. 10 rev Geneva; World Health Organization 1992