Hostname: page-component-5c6d5d7d68-wtssw Total loading time: 0 Render date: 2024-08-22T07:42:25.336Z Has data issue: false hasContentIssue false
  • English
  • Français

Interpreting the Efficacy Findings in the CATIE Study: What Clinicians Should Know

Published online by Cambridge University Press:  07 November 2014

Herbert Y. Meltzer  and
William V. Bobo
Herbert Y. Meltzer*
Affiliation:
Dr. Meltzer is professor of psychiatry and pharmacology, and director of the Psychopharmacology Division at, Vanderbilt University Medical Center in Nashville, Tennessee
William V. Bobo
Affiliation:
Dr. Bobo is assistant director of the Psychopharmacology Division at, Vanderbilt University Medical Center
*
Herbert Y. Meltzer, MD, Psychiatric Hospital at Vanderbilt, 1601 23rd Ave South, Nashville, TN 37215; Tel: 615-327-7049; Fax:, 615-327-7093; E-mail:, herbert.meltzer@vanderbilt.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial was an effectiveness/”pragmatic” clinical trial designed to compare the efficacy, tolerability, and cost-effectiveness of four atypical antipsychotics (olanzapine, quetiapine, risperidone and ziprasidone) and a conventional antipsychotic (perphenazine) for an 18-month period in patients with schizophrenia. The study randomized 1,460 patients with fewer exclusion criteria than in most trials in hopes that this would allow for a more representative sample of outpatients in “real world” practice. Olanzapine demonstrated significant superiority in time to discontinuation for all cause and for lack of efficacy, as well as likelihood of hospitalization for relapse; however, it was associated with a significantly higher rate of metabolic side effects. Perphenazine exhibited comparable effectiveness with quetiapine, risperidone, and ziprasidone, and appeared to be as well tolerated as the atypicals. However, it had the highest rate of drop out due to extrapyramidal symptoms and was restricted to patients who did not have tardive dyskinesia (TD). This article examines the phase 1 CATIE results to guide the clinician in understanding how to interpret the findings, which were intended to be a guide for clinical practice. The nature of the patient population, the doses of drugs relative to one another, inclusion of patients who were treatment resistant, and exclusion of patients with TD from randomization to perphenazine were potential sources of bias in the study. In particular, the use of a higher-than-usual peak dose of olanzapine may have led to the superior results achieved with it. Practical suggestions are given for choice of antipsychotic medication in patients with chronic schizophrenia.

Type
Research Article
Information
CNS Spectrums , Volume 11 , Issue S7 , 2006 , pp. 14 - 24
Copyright
Copyright © Cambridge University Press 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Summerfelt, T, Meltzer, HY. Efficacy vs. effectiveness in psychiatric research. Psychiatric Serv. 1998;49(6):834–835.CrossRefGoogle ScholarPubMed
2.Lieberman, JA, Stroup, TS, McEvoy, JP, et, al, for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209–1223.CrossRefGoogle ScholarPubMed
3.Stroup, TS, McEvoy, JP, Swartz, MS, et al.The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull. 2003;29(1):15–31.CrossRefGoogle ScholarPubMed
4.Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–276.CrossRefGoogle ScholarPubMed
5.Keefe, RS, Mohs, RC, Bilder, RM, et al.Neurocognitive assessment in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project schizophrenia trial: development, methodology, and rationale. Schizophr Bull. 2003;29(1):45–55.CrossRefGoogle ScholarPubMed
6.Woodward, ND, Purdon, SE, Meltzer, HY, Zald, DH. A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol. 2005;8:457–472.CrossRefGoogle ScholarPubMed
7.Jaffe, AB, Levine, J. Efficacy and effectiveness of first- and second-generation antipsychotics in schizophrenia. J Clin Psychiatry. 2003;65(suppl 17):3–6.Google Scholar
8.Glick, I, Marder, SR. Long-term maintenance therapy with quetiapine versus haloperidol decanoate in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry. 2005;66(5):638–641.CrossRefGoogle ScholarPubMed
9.McGrath, BM, Tempier, RP. Patients' opinions of olanzapine and risperidone following long-term treatment: results from a cross-sectional survey. Pharmacopsychiatry. 2005;38(4):147–157.CrossRefGoogle ScholarPubMed
10.Moller, HJ. Novel antipsychotics in the long-term treatment of schizophrenia. World J Biol Psychiatry. 2004;5(1):9–19.CrossRefGoogle ScholarPubMed
11.Schooler, N, Rabinowitz, J, Davidson, M, Emsley, R, et al.Early Psychosis Global Working Group. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. Am J Psychiatry. 2005;162(5):947–953.CrossRefGoogle Scholar
12.Swartz, MS, Perkins, DO, Stroup, TS, McEvoy, JP, Nieri, JM, Haak, DC. Assessing clinical and functional outcomes in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Schizophr Bull. 2003;29(1):33–43.CrossRefGoogle ScholarPubMed
13.Sachdev, P. The current status of tardive dyskinesia. Aus N Z J Psychiatry. 2000;34(3):355–369.CrossRefGoogle ScholarPubMed
14.Margolese, HC, Chouinard, G, Kolivakis, TT, et al.Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia. Can J Psychiatry. 2005;50(11):703–714.CrossRefGoogle ScholarPubMed
15.Stroup, TS, Lieberman, JA, McEvoy, JP, et al.Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipyschotic. Am J Psychiatry. 2006;163:611–622.CrossRefGoogle Scholar
16.McEvoy, JP, Lieberman, JA, Stroup, TS, et al.Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic teatment. Am J Psychiatry. 2006;163:600–610.CrossRefGoogle ScholarPubMed
17.Chakos, M, Lieberman, J, Hoffman, E, Bradford, D, Sheitman, B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry. 2001;158(4):518–526.CrossRefGoogle ScholarPubMed
18.Moller, HJ. Are the new antipsychotics no better than the classical neuroleptics? The problematic answer from the CATIE study. Eur Arch Psychiatry Clin Neurosci. 2005;255(6):371–372.CrossRefGoogle Scholar
19.Ragins, M. Should the CATIE study be a wake-up call? Psychiatr Serv. 2005;56(12):1489.CrossRefGoogle ScholarPubMed
20.Amador, XF, Fitzpatrick, M. Science to services: consumers need “real-world” science. Schizophr Bull. 2003;29(1):133–137.CrossRefGoogle ScholarPubMed
21.Kane, J, Honigfeld, G, Singer, J, Meltzer, H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45(9):789–796.CrossRefGoogle ScholarPubMed
22.Beasley, CM Jr, Tollefson, G, Tran, P, Satterlee, W, Sanger, T, Hamilton, S. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology. 1996;14(2):111–123.CrossRefGoogle ScholarPubMed
23.Beasley, CM Jr, Hamilton, SH, Crawford, AM, et al.Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. Eur Neuropsychopharmacol. 1997;7(2):125–137.CrossRefGoogle ScholarPubMed
24.Breier, A, Berg, PH, Thakore, JH, et al.Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia. Am J Psychiatry. 2005;162(10):1879–1887.CrossRefGoogle ScholarPubMed
25.Claus, A, Bollen, J, de Cuyper, H, et al.Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: A multicentre double-blind comparative study. Acta Psychiatr Scand. 1992;85:295–305.CrossRefGoogle ScholarPubMed
26.Chouinard, G, Jones, B, Remington, G, et al.A Canadian placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol. 1993;13:25–40.CrossRefGoogle ScholarPubMed
27.Duggan, L, Fenton, M, Rathbone, J, Dardennes, R, El-Dosoky, A, Indran, S. Olanzapine for schizophrenia. Cochrane Database Syst Rev. 2005;(1):CD001359.Google Scholar
28.Lee, MA, Thompson, PA, Meltzer, HY. Effects of clozapine on cognitive function in schizophrenia. J Clin Psychiatry. 1994;55(suppl b):82–87.Google ScholarPubMed
29.Meltzer, HY, Sumiyoshi, T, Jayathilake, K. Melperone in the treatment of neuroleptic-resistant schizophrenia. Psychiatr Res. 2001;105:201–209.CrossRefGoogle ScholarPubMed
30.Jayathilake, K, Meltzer, DO, Small, J, Meltzer, HY. Comparison of clozapine and high dose olanzapine in treatment-resistant patients with schizophrenia in a double blind, randomized, 6 month clinical trial. Neuropsychopharmacology. 2005;30(suppl 1):S202.Google Scholar
31.Sumiyoshi, T, Jayathilake, K, Meltzer, HY. A comparison of two doses of melperone, an atypical antipsychotic drug, in the treatment of schizophrenia. Schizophr Res. 2003;62:65–72.CrossRefGoogle ScholarPubMed
32.Meltzer, HY. Treatment-resistant schizophrenia—the role of clozapine. Curr Med Res Opin. 1997;14:1–20.CrossRefGoogle ScholarPubMed
33.de Leon, J, Armstrong, SC, Cozza, KL. The dosing of atypical antipsychotics. Psychosomatics. 2005;46(3):262–273.CrossRefGoogle ScholarPubMed
34.Davis, JM, Chen, N. Dose response and dose equivalence of antipsychotics. J Clin Psychopharmacol. 2004;24(2):192–208.CrossRefGoogle ScholarPubMed
35.Coley, KC, Carter, CS, DaPos, SV, Maxwell, R, Wilson, JW, Branch, RA. Effectiveness of antipsychotic therapy in a naturalistic setting: a comparison between risperidone, perphenazine, and haloperidol. J Clin Psychiatry. 1999;60:850–856.CrossRefGoogle Scholar
36.Geddes, J, Freemantle, N, Harrison, P, Bebbington, P. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ. 2000;321:1371–1376.CrossRefGoogle ScholarPubMed
37.Malla, A, Payne, L. First-episode psychosis: psychopathology, quality of life, and functional outcome. Schizophr Bull. 2005;31:650–671.CrossRefGoogle ScholarPubMed
38.American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27:596–601.CrossRefGoogle Scholar
39.Meltzer, HY. The metabolic consequences of long-term treatment with olanzapine, quetiapine and risperidone: are there differences? Int J Neuropsychopharmacol. 2005;8(2):153–156.CrossRefGoogle ScholarPubMed
40.Newcomer, J. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19(suppl 1):1–93.CrossRefGoogle ScholarPubMed
41.Ader, M, Kim, SP, Catalano, KJ, et al.Metabolic dysregulation with atypical antipsychotics occurs in the absence of underlying disease: a placebo-controlled study of olanzapine and risperidone in dogs. Diabetes. 2005;54(3):862–871.CrossRefGoogle ScholarPubMed
42.Freedman, R. The choice of antipsychotic drugs for schizophrenia. N Engl J Med. 2005;353(12):1286–1288.CrossRefGoogle ScholarPubMed
43. International Psychopharmacology Project. IPAP schizophrenia algorithm. Available at: http://www.ipap.org/schiz/contentlist.php). Accessed: February 2, 2006.Google Scholar
44.Potkin, SG, Saha, AR, Kujawa, MJ, et al.Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2003;60(7):681–690.CrossRefGoogle ScholarPubMed
45.Tharyan, P, Adams, CE. Electroconvulsive therapy for schizophrenia. Cochrane Database Syst Rev. 2005;(2):CD000076.Google Scholar
46.Mauskopf, J, Muroff, M, Gibson, PJ, Grainger, DL. Estimating the costs and benefits of new drug therapies: Atypical antipsychotic drugs for schizophrenia. Schizophr Bull. 2002;28(4):619–635.CrossRefGoogle ScholarPubMed
47.Revicki, DA. Cost effectiveness of the newer atypical antipsychotics: a review of the pharmacoeconomic research evidence. Curr Opin Investig Drugs. 2001;2(1):110–117.Google ScholarPubMed
48.Tunis, SL, Ascher-Svanum, H, Stensland, M, Kinon, BJ. Assessing the value of antipsychotics for treating schizophrenia: The importance of evaluating and interpreting the clinical significance of individual service costs. Pharmacoeconomics. 2004;22(1):1–8.CrossRefGoogle ScholarPubMed
49.Rosenheck, RA. Cost-effectiveness of atypical antipsychotics in the CATIE schizophrenia trial. Neuropsychopharmacology. 2005;(suppl 1):S32.Google Scholar
50.Harrington, C, Gregorian, R, Gemmen, E, et al. The Lewin Group. Access and utilization of new antidepressant and antipsychotic medications. Falls Church, Va: The Office of the Assistant Secretary for Planning and Evaluation, the National Institute of Mental Health, US Dept. of Health and Human Services; 2000. Available at: http://aspe.hhs.gov/health/reports/Psychmedaccess/). Accessed: February 13, 2006.Google Scholar
51. IMS Health. Atypical antipsychotics: generating evidence to inform policy and practice. Available at: http://research.imshealth.com/research_schizophrenia.htm. Accessed February 14, 2006.Google Scholar
52.Geddes, J. Generalizing evidence to inform policy and practice: the example of the second generation ‘atypical’ antipsychotics. Schizophr Bull. 2003;29:105–114.CrossRefGoogle ScholarPubMed