Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-28T01:26:22.389Z Has data issue: false hasContentIssue false
  • English
  • Français

Aripiprazole for Patients with Schizophrenia and Schizoaffective Disorder: An Open-Label, Randomized, Study Versus Haloperidol

Published online by Cambridge University Press:  07 November 2014

Irismar Reis de Oliveira ,
Hélio Elkis ,
Wagner Farid Gattaz ,
Ana Cristina Chaves ,
Eduardo Pondé de Sena ,
Fabio Gomes de Matos e Souza ,
João Alberto Campos ,
João Romildo Bueno ,
Jorge Alberto Costa e Silva  and
Mário Rodrigues Louzã
...Show all authors
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction: Aripiprazole, a dopamine D2 receptor partial agonist, has also partial agonist activity at serotonin (5-HT)1A receptors and antagonist activity at 5-HT2A receptors.

Methods: In this 8-week, multicenter, randomized, parallel-group, open-label, flexible-dose study, patients diagnosed with schizophrenia or schizoaffective disorder were randomized to aripiprazole 15–30 mg/day or haloperidol 10–15 mg/day.

Results: Patients treated with both aripiprazole and haloperidol improved from baseline in Positive and Negative Syndrome Scale total, positive, and negative scores as well as in Clinical Global Impressions scores (all P<.001). At the end of the study, the percentage of patients classified as responders—according to ≥40% reduction in the Positive and Negative Syndrome Scale negative subscale score—was significantly higher in the aripiprazole group (20%) than in the haloperidol group (0%) (P<.05). Additionally, a higher number of patients receiving haloperidol required more anticholinergic medications (P<.001) than aripiprazole-treated patients, whereas more aripiprazole (45.5%) than haloperidol-treated patients (12.9%) required benzodiazepines (P=.002). At endpoint, rates of preference of medication were higher in the aripiprazole group (63.2%) than in the haloperidol group (21.7%), as expressed by patients and caregivers (P=.001).

Conclusion: Aripiprazole and haloperidol had similar efficacy in terms of reduction of overall psychopathology. Although aripiprazole has been demonstrated to be superior concerning negative symptoms and in terms of tolerability (extrapyramidal symptoms) and preferred by patients and caregivers than haloperidol, significantly more aripiprazole-treated patients required benzodiazepines.

Type
Original Research
Information
CNS Spectrums , Volume 14 , Issue 2 , February 2009 , pp. 93 - 102
Copyright
Copyright © Cambridge University Press 2009

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

REFERENCES

1.De Oliveira, IR, Juruena, MF. Treatment of psychosis: 30 years of progress. J Clin Pharm Ther. 2006; 31: 523–534.CrossRefGoogle ScholarPubMed
2.Tandon, R, Belmaker, RH, Gattaz, WF, et al. World Psychiatric Association Pharmacopsychiatry Section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia. Schizophr Res. 2008; 100: 20–38.Google Scholar
3.Goff, DC, Evins, AE. Negative symptoms in schizophrenia: neurobiological models and treatment response. Harv Rev Psychiatry. 1998; 6: 59–77.Google Scholar
4.Siris, SG. Depression in schizophrenia: perspective in the era of “atypical” antipsychotic agents. Am J Psychiatry. 2000; 157: 1379–1389.Google Scholar
5.Keefe, RS, Silva, SG, Perkins, DO, Lieberman, JA. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull. 1999; 25: 201–;222.Google Scholar
6.Meltzer, HY. Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology (Berl). 1989; 99(suppl): S18–;S27.Google Scholar
7.Kapur, S, Seeman, P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci. 2000; 25: 161–166.Google ScholarPubMed
8.Lahti, AC, Weiler, MA, Corey, PK, Lahti, RA, Carlsson, A, Tamminga, CA. Antipsychotic properties of the partial dopamine agonist (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine(preclam ol) in schizophrenia. Biol Psychiatry. 1998; 43: 2–11.Google Scholar
9.Naber, D, Lambert, M. Aripiprazole: a new atypical antipsychotic with a different pharmacological mechanism. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28: 1213–1219.Google Scholar
10.Kikuchi, T, Tottori, K, Uwahodo, Y, et al. 7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1 H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther. 1995; 274: 329–336.Google Scholar
11.Burris, KD, Molski, TF, Xu, C, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther. 2002; 302: 381–389.CrossRefGoogle ScholarPubMed
12.Jordan, S, Koprivica, V, Chen, R, Tottori, K, Kikuchi, T, Altar, CA. The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol. 2002; 441: 137–140.Google Scholar
13.Hirose, T, Uwahodo, Y, Yamada, S, et al. Mechanism of action of aripiprazole predicts clinical efficacy and a favourable side-effect profile. J Psychopharmacol. 2004; 18: 375–383.Google Scholar
14.Sovner, R, Parnell-Sovner, N. Use of buspirone in the treatment of schizophrenia. J Clin Psychopharmacol. 1989; 9: 61–62.CrossRefGoogle ScholarPubMed
15.Millan, MJ. Improving the treatment of schizophrenia: focus on serotonin (5-HT)(1 A) receptors. J Pharmacol Exp Ther. 2000; 295: 853–861.Google Scholar
16.Richelson, E. Receptor pharmacology of neuroleptics: relation to clinical effects. J Clin Psychiatry. 1999; 60(suppl 10):5–14.Google ScholarPubMed
17.Kane, JM, Carson, WH, Saha, AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002; 63: 763–771.CrossRefGoogle ScholarPubMed
18.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: 681–690.Google Scholar
19.Tandon, R, Marcus, RN, Stock, EG, et al. A prospective, multicenter, randomized, parallel-group, open-label study of aripiprazole in the management of patients with schizophrenia or schizoaffective disorder in general psychiatric practice: Broad Effectiveness Trial With Aripiprazole (BETA). Schizophr Res. 2006; 84: 77–89.Google Scholar
20.Cutler, AJ, Marcus, RN, Hardy, SA, O'Donnel, A, Carson, WH, McQuade, RD. The efficacy and safety of lower doses of aripiprazole for the treatment of patients with acute exacerbation of schizophrenia. CNS Spectr. 2006; 11: 691–702.Google Scholar
21.McEvoy, JP, Daniel, DG, Carson, WH Jr, McQuade, RD, Marcus, RN. A randomized, doubleblind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia. J Psychiatr Res. 2007; 41: 895–905.CrossRefGoogle ScholarPubMed
22.Wolf, J, Janssen, F, Lublin, H, et al. A prospective, multicentre, open-label study of aripiprazole in the management of patients with schizophrenia in psychiatric practice in Europe: Broad Effectiveness Trial with Aripiprazole in Europe (EU-BETA). Curr Med Res Opin. 2007; 23: 2313–2323.Google Scholar
23.Pigott, TA, Carson, WH, Saha, AR, Torbeyns, AF, Stock, EG, Ingenito, GG; Aripiprazole Study Group. Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study. J Clin Psychiatry. 2003; 64: 1048–1056.Google Scholar
24.Kasper, S, Lerman, MN, McQuade, RD, et al. Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol. 2003; 6: 325–337.Google Scholar
25.Chan, HY, Lin, WW, Lin, SK, et al. Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control: a randomized trial. J Clin Psychiatry. 2007; 68: 29–36.CrossRefGoogle ScholarPubMed
26.Kane, JM, Meltzer, HY, Carson, WH Jr, McQuade, RD, Marcus, RN, Sanchez, R; the Aripiprazole Study Group. Aripiprazolefo treatment-resistant schizophrenia: results of a multicenter, randomized, double-blind, comparison study versus perphenazine. J Clin Psychiatry. 2007; 68: 213–223.CrossRefGoogle Scholar
27.Marder, SR, McQuade, RD, Stock, E, et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res. 2003; 61: 123–136.Google Scholar
28.Chaves, AC, Seeman, MV. Sex selection bias in schizophrenia antipsychotic trials. J Clin Pshychopharmacol. 2006; 26: 489–494.Google Scholar
29.Kerwin, R, Millet, B, Herman, E, et al. A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study. Eur Psychiatry. 2007; 22: 433–443.Google Scholar
30.Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.Google Scholar
31.Kay, SR, Fiszbein, A, Opler, LA. The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia. Schizophr Bull. 1987; 13: 261–276.Google Scholar
32.Kay, SR, Opler, LA, Lindenmayer, JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatric Res. 1988; 23: 99–110.Google Scholar
33.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
34.Guy, W. ECDEU Assessment Manual for Psychopharmacology: Revised. (DHEW Publication No. ADM 76-338) Rockville, Md: National Institute of Mental Health; 1976.Google Scholar
35.Ware, JE Jr, Sherbourne, CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992; 30: 473–483.Google Scholar
36.Simpson, GM, Angus, JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand. 1970; 45(suppl 212): 11–19.Google Scholar
37.Barnes, TR. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989; 154: 672–676.CrossRefGoogle ScholarPubMed
38.Lingjaerde, O, Ahlfors, UG, Bech, P. The UKU Side-Effect Rating Scale. Acta Psychiatr Scand. 1987; 76(suppl 334): 81–94.Google Scholar
39.Moher, D, Schulz, KF, Altman, D; CONSORT Group. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA. 2001; 285: 1987–1991.Google Scholar
40.Leucht, S, Pitchel-Walz, G, Engel, RR, Kissling, W. Amisulpride, an unusual “atypical” antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry. 2002; 159: 180–190.CrossRefGoogle ScholarPubMed
41.Marder, SR, West, B, Lau, GS, et al. Aripiprazole effects in patients with acute schizophrenia experiencing higher or lower agitation: a post hoc analysis of 4 randomized, placebocontrolled clinical trials. J Clin Psychiatry. 2007; 68: 662–668.Google Scholar
42.Rosa, AR, Sanchez-Moreno, J, Martinez-Aran, A, et al. Validity and reliability of the Functioning Assessment Short Test (FAST) in bipolar disorder. Clin Pract Epidemol Ment Health. 2007; 3: 5.Google Scholar
43.Shimoda, K, Someya, T, Morita, S, et al. Lower plasma levels of haloperidol in smoking than in nonsmoking schizophrenic patients. Ther Drug Monit. 1999; 21: 293–296.Google Scholar