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Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial

  • Ragy R. Girgis (a1), Michael R. Phillips (a2), Xiaodong Li (a1), Kejin Li (a3), Huiping Jiang (a1), Chengjing Wu (a3), Naihua Duan (a1), Yajuan Niu (a3) and Jeffrey A. Lieberman (a1)...

Abstract

Background

The differential effects of so-called ‘first- and second-generation’ antipsychotic medications, when given in the first episode, on the long-term outcome of schizophrenia remain to be elucidated.

Aims

We compared the 9-year outcomes of individuals initially randomised to clozapine or chlorpromazine.

Method

One-hundred and sixty individuals with treatment-naive, first-episode schizophrenia or schizophreniform disorder in a mental health centre in Beijing, China were randomised to clozapine or chlorpromazine treatment for up to 2 years, followed by up to an additional 7 years of naturalistic treatment. The primary outcome was remission status for individuals in each group.

Results

Individuals in both groups spent essentially equal amounts of time in each clinical state over the follow-up time period (remission, 78%; intermediate, 8%; relapse, 14%). There were no significant differences on other measures of illness severity. The clozapine group was more likely than the chlorpromazine group to remain on the medication to which they were originally assigned (26% v. 10%, P = 0.01). There were no significant differences between the two groups on other secondary efficacy outcomes.

Conclusions

These findings support the comparability in effectiveness between antipsychotic medications but with slightly greater tolerability of clozapine in the treatment of first-episode psychosis.

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Copyright

Corresponding author

Jeffrey A. Lieberman, MD, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, 1051 Riverside Dr., Unit 4, New York, NY 10032, USA. Email: jlieberman@columbia.edu

Footnotes

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Aspects of this study have been presented at the 2009 Annual Meeting of the American Psychiatric Association (San Francisco, USA, 17 May), the 2009 Annual Meeting of the New York County District Branch of the American Psychiatric Association (New York, USA, 30 April) and the 11th Annual Symposium on Statistics in Psychiatry (Philadelphia, USA, 11 May 2009).

See editorials, pp. 266–268 and 269–271, this issue.

This work was supported by funds from the Novartis Pharmaceutical Company, which also supplied medications.

Declaration of interest

R.R.G. has received research support from Janssen and Lilly through APIRE and a travel stipend from Lilly, Forest, and Elsevier Science through the Society of Biological Psychiatry. N.D. has received research support from Pfizer. J.A.L. has received research grant support from Acadia, Allon, AstraZeneca, Bristol-Myers Squibb, Forest Labs, GlaxoSmithKline, Janssen, Merck, Organon, Pfizer, and Wyeth. He has acted as a consultant and an advisory board member for Astra-Zeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, and Pfizer; has been a consultant for Cephalon, Johnson & Johnson and Novartis; an advisory board member for Bioline, Forest Labs, Lundbeck, Organon and Wyeth; and a DSMB member for Solvay. J.A.L. has received no direct financial compensation or salary support for participation in research, consulting, advisory board or DSMB activities. J.A.L. holds a patent from Repligen.

Footnotes

References

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1 McGlashan, TH, Johannessen, JO. Early detection and intervention with schizophrenia: rationale. Schizophr Bull 1996; 22: 201–22.
2 Wyatt, RJ. Neuroleptics and the natural course of schizophrenia. Schizophr Bull 1991; 17: 325–51.
3 Emsley, R, Oosthuizen, PP, Kidd, M, Koen, L, Niehaus, DJ, Turner, HJ. Remission in first-episode psychosis: predictor variables and symptom improvement patterns. J Clin Psychiatry 2006; 67: 1707–12.
4 Marshall, M, Lewis, S, Lockwood, A, Drake, R, Jones, P, Croudace, T. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry 2005; 62: 975–83.
5 Perkins, D, Lieberman, J, Gu, H, Tohen, M, McEvoy, J, Green, A, et al. Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders. Br J Psychiatry 2004; 185: 1824.
6 Perkins, DO, Gu, H, Boteva, K, Lieberman, JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry 2005; 162: 1785–804.
7 Lieberman, JA, Tollefson, GD, Charles, C, Zipursky, R, Sharma, T, Kahn, RS, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005; 62: 361–70.
8 Lieberman, JA, Bymaster, FP, Meltzer, HY, Deutch, AY, Duncan, GE, Marx, CE, et al. Antipsychotic drugs: comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection. Pharmacol Rev 2008; 60: 358403.
9 Crespo-Facorro, B, Perez-Iglesias, R, Ramirez-Bonilla, M, Martinez-Garcia, O, Llorca, J, Vazquez-Barquero, JL. A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode nonaffective psychosis. J Clin Psychiatry 2006; 67: 1511–21.
10 Emsley, RA. Risperidone in the treatment of first-episode psychotic patients: a double-blind multicenter study. Risperidone Working Group. Schizophr Bull 1999; 25: 721–9.
11 Moller, HJ, Riedel, M, Jager, M, Wickelmaier, F, Maier, W, Kuhn, KU, et al. Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia. Int J Neuropsychopharmacol 2008; 11: 985–97.
12 Lieberman, JA, Tollefson, G, Tohen, M, Green, AI, Gur, RE, Kahn, R, et al. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry 2003; 160: 1396–404.
13 Sanger, TM, Lieberman, JA, Tohen, M, Grundy, S, Beasley, C Jr, Tollefson, GD. Olanzapine versus haloperidol treatment in first-episode psychosis. Am J Psychiatry 1999; 156: 7987.
14 Gaebel, W, Riesbeck, M, Wolwer, W, Klimke, A, Eickhoff, M, von Wilmsdorff, M, et al. Maintenance treatment with risperidone or low-dose haloperidol in first-episode schizophrenia: 1-year results of a randomized controlled trial within the German Research Network on Schizophrenia. J Clin Psychiatry 2007; 68: 1763–74.
15 Schooler, N, Rabinowitz, J, Davidson, M, Emsley, R, Harvey, PD, Kopala, L, et al. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. Am J Psychiatry 2005; 162: 947–53.
16 Green, AI, Lieberman, JA, Hamer, RM, Glick, ID, Gur, RE, Kahn, RS, et al. Olanzapine and haloperidol in first episode psychosis: two-year data. Schizophr Res 2006; 86: 234–43.
17 Kahn, RS, Fleischhacker, WW, Boter, H, Davidson, M, Vergouwe, Y, Keet, IP, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008; 371: 1085–97.
18 Lieberman, JA, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209–23.
19 Jones, PB, Barnes, TR, Davies, L, Dunn, G, Lloyd, H, Hayhurst, KP, et al. Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87.
20 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: 789–96.
21 Sikich, L, Frazier, JA, McClellan, J, Findling, RL, Vitiello, B, Ritz, L, et al. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry 2008; 165: 1420–31.
22 Leucht, S, Corves, C, Arbter, D, Engel, RR, Li, C, Davis, JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 2009; 373: 3141.
23 Breier, A, Hamilton, SH. Comparative efficacy of olanzapine and haloperidol for patients with treatment-resistant schizophrenia. Biol Psychiatry 1999; 45: 403–11.
24 Tollefson, GD, Birkett, MA, Kiesler, GM, Wood, AJ. Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine. Biol Psychiatry 2001; 49: 5263.
25 Lieberman, JA, Phillips, M, Gu, H, Stroup, S, Zhang, P, Kong, L, et al. Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine. Neuropsychopharmacology 2003; 28: 9951003.
26 Phillips, MR, Xiong, W, Zhao, ZA. Issues Involved in the Use of Scales for the Assessment of Negative and Positive Symptoms in Psychotic Patients [in Chinese]. Hubei Science and Technology Publishing House, 1990.
27 First, MB, Spitzer, RL, Gibbon, M, Williams, JBW. Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press, 1996.
28 Phillips, MR, Xiong, W, Wang, RW, Gao, YH, Wang, XQ, Zhang, NP. Reliability and validity of the Chinese versions of the Scales for Assessment of Positive and Negative Symptoms. Acta Psychiatr Scand 1991; 84: 364–70.
29 Guy, W. ECDEU Assessment Manual for Psychopharmacology. Revised DHEW Pub. (ADM). National Institute for Mental Health, 1976.
30 Jones, SH, Thornicroft, G, Coffey, M, Dunn, G. A brief mental health outcome scale – reliability and validity of the Global Assessment of Functioning (GAF). Br J Psychiatry 1995; 166: 654–9.
31 Simpson, GM, Angus, JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970; 212: 11–9.
32 Simpson, GM, Lee, JH, Zoubok, B, Gardos, G. A rating scale for tardive dyskinesia. Psychopharmacology (Berl) 1979; 64: 171–9.
33 Little, RJA, Rubin, DB. Statistical Analysis with Missing Data. John Wiley & Sons, 2002.
34 Agid, O, Remington, G, Kapur, S, Arenovich, T, Zipursky, RB. Early use of clozapine for poorly responding first-episode psychosis. J Clin Psychopharmacol 2007; 27: 369–73.
35 Gitlin, M, Nuechterlein, K, Subotnik, KL, Ventura, J, Mintz, J, Fogelson, DL, et al. Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia. Am J Psychiatry 2001; 158: 1835–42.
36 Robinson, D, Woerner, MG, Alvir, JM, Bilder, R, Goldman, R, Geisler, S, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 1999; 56: 241–7.
37 Szymanski, SR, Cannon, TD, Gallacher, F, Erwin, RJ, Gur, RE. Course of treatment response in first-episode and chronic schizophrenia. Am J Psychiatry 1996; 153: 519–25.
38 Lehman, AF, Lieberman, JA, Dixon, LB, McGlashan, TH, Miller, AL, Perkins, DO, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry 2004; 161: 156.
39 Penn, DL, Waldheter, EJ, Perkins, DO, Mueser, KT, Lieberman, JA. Psychosocial treatment for first-episode psychosis: a research update. Am J Psychiatry 2005; 162: 2220–32.
40 Kane, JM. Tardive dyskinesia rates with atypical antipsychotics in adults: prevalence and incidence. J Clin Psychiatry 2004; 65 (suppl 9): 1620.
41 Alvir, JM, Lieberman, JA, Safferman, AZ, Schwimmer, JL, Schaaf, JA. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med 1993; 329: 162–7.
42 Allison, DB, Mentore, JL, Heo, M, Chandler, LP, Cappelleri, JC, Infante, MC, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156: 1686–96.
43 Newcomer, JW. Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry. 2007; 68 (suppl 4): 813.
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Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial

  • Ragy R. Girgis (a1), Michael R. Phillips (a2), Xiaodong Li (a1), Kejin Li (a3), Huiping Jiang (a1), Chengjing Wu (a3), Naihua Duan (a1), Yajuan Niu (a3) and Jeffrey A. Lieberman (a1)...
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eLetters

Re:Clozapine v. chlorpromazine in treatment na?ve, first-episode schizophrenia

Jeffrey A, Lieberman, Department of Psychiatry
16 November 2011

We appreciate Dr. Nebhinani's interest in our study (1) as well as the opportunity to respond to the six comments. First, our study was analyzed using the intent-to-treat principle. Implicit in the intent-to-treat principle is that the outcome is not the effect of treatment per se,but rather the effect of initial assignment irrespective of treatment(s) received (2). Second, we agree that there are controversies as to the definition of first-episode psychosis (3). As reported by Breitborde et al., 'duration of psychosis' possesses the most construct validity, followed by other criteria, such as 'duration of antipsychotic medication use' and 'first treatment contact' (3). We conservatively identified first-episode subjects using both duration of psychosis and duration of antipsychotic medication use as two of our criteria. Furthermore, we included a maximum age criterion (i.e., 40 years old at the time when symptoms began) and symptom criteria to further narrow and restrict our study participants to those who are most likely to have first-episode psychosis. Third, our conclusions and main outcomes used the intent-to-treat principle and were based on the entire sample, rather than primarilybased on the 29 individuals who remained on their originally assigned medication after nine years. We described characteristics of this smaller group, without an intent to generalize, due to the obvious lack of representativeness in this subgroup of patients. Furthermore, it is important to note that the generalizability of a clinical finding is determined by the representativeness of the sample observed, rather than the sample size observed.

Fourth, as described in the article, we did not have any missing baseline data for weight for those subjects whose weights were included inour metabolic analyses. In addition, we disagree that we indicated that there were no differences in side effects between the two groups. Rather, we descriptively reported differences in tardive dyskinesia and agranulocytosis between the two treatment groups. Finally, we did not claim that the metabolic findings in this study are generalizable, but we do agree with Dr. Nebhinani that it would have been valuable to report on additional metabolic indices (e.g., lipids and blood pressure). Unfortunately, these data were not available.

Fifth, we reported the average percentages of time that participants in each group took other antipsychotic medications or resumed the originalmedication during the follow-up period, rather than the percentages of individuals in each group on any treatment regimen at 9 year follow-up. Therefore, the results (55% for the chlorpromazine group and 73% for the clozapine group) represent averages over the entire seven year period, rather than cross-sectional results at the nine year follow-up time point.The clinical status of these patients over the entire nine years of the study were reported in detail in the article, both in terms of symptom measures, functional status, global clinical status, medication status, side effects, remission status, and status in the study (i.e., still in the study or dropped out).

Finally, we agree that individuals with schizophreniform disorder arelikely to have better outcomes than individuals with schizophrenia, by definition. However, all diagnoses were randomly and equally assigned to the two treatment groups. Therefore, including this diagnosis is unlikely to have affected the between-group outcomes of this study.

Ragy R. Girgis, Naihua Duan, Jeffrey A. Lieberman. Department of Psychiatry, College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute

1.Girgis RR, Phillips MR, Li X, Li K, Jiang H, Wu C, et al. Clozapine v. chlorpromazine in treatment-naive, first-episode schizophrenia: 9-year outcomes of a randomised clinical trial. Br J Psychiatry. 2011. 2.Lachin JM. Statistical considerations in the intent-to-treat principle.Control Clin Trials. 2000;21(3):167-89. 3.Breitborde NJK, Srihari VH, Woods SW. Review of the operational definition for first-episode psychosis. Early Interv Psychia. 2009;3(4):259-65.

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Conflict of interest: None declared

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Moral, Ethical and Geopolitical Considerations of Chinese Research.

David Denton, CT2 Psychiatry
02 November 2011

Dear Editor,

I am troubled by the provenance of the Girgis et al study published in the BJPsych, October 2011 and particularly struggle with the wider geopolitical, ethical and moral dilemmas.

Whilst learned colleagues will comment on the merits of a small naturalistic study, with questionable methodology, lack of power calculation, consideration of confidence intervals, p values, genetics andcomparability, I would also like to also consider the importance of the political and ethical landscape under which this study was conducted.

It is estimated that one-third of China's 7.8 million persons with schizophrenia and 95% of those with affective disorders have never received formal psychiatric diagnosis or treatment. 1

Psychiatry and the pharmaceutical industry in China has had a fairly chequered past and it is not clear how much these problems have improved over the last few years.

Amongst these include Robin Munro, former Director of the Hong Kong Office of Human Rights Watch who drew worldwide attention to the abuses offorensic psychiatry in China in general, and of Falun Gong practitioners in particular.2

We do not know in this study whether the Novartis medication was manufactured in China. If so, I would be concerned by Manufacturing Practice (GMP) in China since 1995 which has seen widespread corruption which has severely undermined the effectiveness of this certification. In 2007, the SFDA reinforced its administrative oversight in an effort to reduce corruption by revising the practices of GMP regulation.3

Zheng Xiaoyu , director of the State Food and Drug Administration of the People's Republic of China was sentenced to death in the first instance trial at Beijing No.1 Intermediate Court on May 29, 2007 for corruption.4,5 It is within this moral landscape that one must be cautiousof research coming from this region.

China is expected to become the world's third-largest prescription drug market in 2011 and it appears that its pharmaceutical revenue is growing fast and that the market there may double by 2013.6

Whilst applauding the BJPsych and RCPsych efforts to work constructively with our Chinese counterparts, we must also consider in a transparent way the human right abuses, potential corruption and the influence of the large influx of research and development money in China with a view to companies maximising profits in todays economic climate andthe influence this has on research.

As doctors we need to continue to advocate on behalf of patients withserious mental illness and cast a critical eye on such activities around the world whilst respectfully guiding such fledgling research in developing areas of the globe.

China's central government in 2009 announced, a major overhaul of itshealth-care system is currently taking place with basic medical insurance coverage for 90% of its 1.3 billion people. The government has said it plans to increase its spending on health care by 16% in 2011, to roughly $26 billion. Part of that goes to reimbursements for pharmaceuticals.7

To conclude, further research and collaboration with the Peoples Republic of China must be more closely scrutinised whilst they continue toimprove infrastructure and develop a moral and ethical tradition guided bythe international community whilst respecting cultural identity.

1.Murray, C.J.L., and Lopez A.D. (1996) The global burden of disease.Cambridge: Harvard University Press.

2.Munro R: Judicial psychiatry in China and its political abuses. Columbia Journal of Asian Law 14:1-128, 2000

3.Price Waterhouse Coopers; Investing in China's Pharmaceutical Industry - 2nd Edition. http://www.pwc.com/en_GX/gx/pharma-life-sciences/assets/en-pharma_03-26-small.pdf

4.http://www.chinadaily.com.cn/china/2007-07/10/content_5424937.htm

5.http://www.thepharmaletter.com/file/42943/sfda-unsatisfactory-drug-regulation-in-china.html

6.Merk Annual Report 2010;Audited by KPMG forecast for the Pharmaceuticals business sector. http://merck.onlinereport.eu/2010/ar/managementreport/reportonexpecteddevelopments/pharmaceuticals.html



7.http://online.wsj.com/article/SB10001424052748703858404576213883923849302.html

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Conflict of interest: None declared

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Clozapine v. chlorpromazine in treatment na?ve, first-episode schizophrenia

Naresh Nebhinani, Psychiatrist
05 October 2011

Girgis et al1 presented the data with respect to the usefulness of clozapine versus chlorpromazine in patients with first episode schizophrenia. Authors must be complemented for conducting a follow-up study of the same cohort after 9 years and being able to have such a high retention rate. Further, the study provides information with respect to the naturalistic setting reflecting the true clinical situation and authors have also taken care of possible confounders with appropriate statistical analysis along with proper explanation for the same. However, there are certain issues with the study. First, the title of the article is somewhat misleading because the randomization phase of the study was only for the initial 2 years and after that the patients have received treatment at the discretion of the clinicians. The title would have been appropriate if the authors were describing the outcome in terms of efficacy/effectiveness and side effect profile by using the survival analysis focusing on either of the medications. But actually the authors described the effect of use of clozapine and chlorpromazine for the initial 1 years and outcome at the 9 year follow-up. Second, we need to understand that there are controversies in relation to the definition of first episode psychosis and the definition used by the authors may appear to be very broad2. Third, the sample size in each treatment group which remained on the same medication [clozapine (N=21) or chlorpromazine group (N=8)] at the 9 year follow-up is too small to generalize. Hence, to conclude that there is no difference between clozapine and chlorpromazine with respect to effectiveness would be wrong. Ideally to make such conclusion, a larger sample size is required which would continue the medication for the evaluation duration. Fourth, the authors also conclude that there is no difference in the metabolic and other side effects between the 2 groups, besides having incomplete baseline data for weight there is no mention of other metabolic variables such as high density lipoprotein, triglyceride, and blood pressure. Fifth, more than half of study sample (55% in chlorpromazine group v. 73% in clozapine group) was not on any antipsychotic medication at 9 year follow-up, but authors have not elaborated about their clinical status. Last of all, one-forth of participants (24%) was diagnosed with schizophreniform disorder which might have directly affected the outcome as this group of disorders is considered to have better outcome than schizophrenia.

References

1. Girgis RR, Phillips MR, Li X, Li K, Jiang H, Wu C, Duan N, Niu Y, Lieberman JA. Clozapine v. chlorpromazine in treatment-naive, first- episode schizophrenia: 9-year outcomes of a randomised clinical trial. Br J Psychiatry 2011; 199: 281-288.

2. Breitborde NK, Srihari VH, Woods SW. Review of the operational definition for first- episode psychosis. Early Intervention in Psychiatry 2009; 3: 259-265.
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Conflict of interest: None Declared

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