利培酮或低剂量氟哌啶醇用于首发精神分裂症的维持治疗：德国精神分裂症研究网络内一项随机对照试验的1年结果

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.

作者信息

Gaebel Wolfgang, Riesbeck Mathias, Wölwer Wolfgang, Klimke Ansgar, Eickhoff Matthias, von Wilmsdorff Martina, Jockers-Scherübl Maria C, Kühn Kai-Uwe, Lemke Matthias, Bechdolf Andreas, Bender Stefan, Degner Detlef, Schlösser Ralf, Schmidt Lutz G, Schmitt Andrea, Jäger Markus, Buchkremer Gerd, Falkai Peter, Klingberg Stefan, Köpcke Wolfgang, Maier Wolfgang, Häfner Heinz, Ohmann Christian, Salize Hans J, Schneider Frank, Möller Hans-Jürgen

机构信息

Department of Psychiatry and Psychotherapy, Heinrich-Heine-University of Düsseldorf, Rhineland State Clinics Düsseldorf, Düsseldorf, Germany.

出版信息

J Clin Psychiatry. 2007 Nov;68(11):1763-74. doi: 10.4088/jcp.v68n1116.

DOI:10.4088/jcp.v68n1116

PMID:18052570

Abstract

OBJECTIVE

Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested.

METHOD

Between November 2000 and May 2004, 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals. 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria. In the randomized controlled trial, double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for analysis. For 127 patients, this was a continuation trial after 8 weeks of randomized, double-blind, acute treatment with the same drugs; 24 patients were additionally randomly assigned after open acute treatment.

RESULTS

With both antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved. Additionally, according to 2 post hoc defined measures of "marked clinical deterioration," significant differences occurred neither in the 2 respective deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time until deterioration. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Extrapyramidal symptoms were slightly higher with haloperidol. The overall dropout rate of 68%, however, was not significantly different between the 2 drug groups.

CONCLUSION

Against the background of an overall favorable outcome, the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia. Possible design-related reasons for this finding are discussed. With regard to the high dropout rate, special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment.

CLINICAL TRIALS REGISTRATION

ClinicalTrials.gov identifier: NCT00159081.

摘要

目的

已证实第二代抗精神病药物（SGA）在预防复发方面优于第一代抗精神病药物，主要体现在多发作患者中。实践指南推荐SGA作为一线治疗药物，尤其是在首发患者中，尽管针对这一群体的证据仍然有限。因此，对首发精神分裂症患者在接受利培酮维持治疗下的1年复发率是否低于低剂量氟哌啶醇进行了检验。

方法

在2000年11月至2004年5月期间，对德国13家精神病学大学医院的住院部1372例患者进行了资格筛查。根据ICD - 10 F20标准，159例症状缓解的患者在首次精神分裂症急性发作治疗后入组。在随机对照试验中，利培酮或氟哌啶醇的双盲抗精神病治疗以2至4毫克/天的目标剂量维持1年。151例患者符合分析条件。对于127例患者，这是在使用相同药物进行8周随机双盲急性治疗后的延续试验；24例患者在开放急性治疗后另外随机分配。

结果

使用两种抗精神病药物（利培酮，N = 77；氟哌啶醇，N = 74）均未出现复发。此外，根据两项事后定义的“明显临床恶化”指标，在各自的两种恶化率（利培酮 = 9%/23%；氟哌啶醇 = 8%/22%）以及直至恶化的时间方面均未出现显著差异。两种抗精神病药物在显著减轻症状和改善生活质量方面同样有效。氟哌啶醇的锥体外系症状略高。然而，两个药物组68%的总体脱落率并无显著差异。