pregnenolone 和脱氢表雄酮作为精神分裂症和分裂情感障碍的辅助治疗：一项为期 8 周、双盲、随机、对照、2 中心、平行组试验。

Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial.

机构信息

Department of Psychiatry, The Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel.

出版信息

J Clin Psychiatry. 2010 Oct;71(10):1351-62. doi: 10.4088/JCP.09m05031yel. Epub 2010 Jun 15.

DOI:10.4088/JCP.09m05031yel

PMID:20584515

Abstract

OBJECTIVE

Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are reported to have a modulatory effect on neuronal excitability, synaptic plasticity, and response to stress; they are associated with mood regulation and cognitive performance. We investigated the influence of PREG and DHEA on psychotic symptoms and cognitive functioning as an add-on to ongoing antipsychotic treatment of patients with chronic schizophrenia or schizoaffective disorder.

METHOD

This 8-week, double-blind, randomized, placebo-controlled, 2-center study compared 30 mg/d of PREG (PREG-30), 200 mg/d of PREG (PREG-200), 400 mg/d of DHEA, and placebo as an adjunctive treatment of 58 chronic schizophrenia or schizoaffective disorder patients (DSM-IV). The data were collected from February 2005 until June 2007. The outcome measures were symptomatic and neurocognitive changes, functioning, and tolerability as assessed primarily by the Clinical Global Impressions-Severity of Illness scale and the Positive and Negative Syndrome Scale. Analyses are presented for 44 patients who completed 8 weeks of treatment and for 14 noncompleters.

RESULTS

Compared with subjects who received placebo, those administered PREG-30 had significant reductions in positive symptom scores and extrapyramidal side effects (EPS) and improvement in attention and working memory performance, whereas subjects treated with PREG-200 did not differ on outcome variable scores for the study period. The general psychopathology severity and general functioning of patients receiving placebo and PREG-30 improved more than that of those subjects treated with DHEA, while EPS improved more in subjects treated with DHEA than in patients receiving placebo. Negative symptoms and akathisia were not significantly benefited by any treatment. The administration of PREG and DHEA was well tolerated.

CONCLUSIONS

Low-dose PREG augmentation demonstrated significant amelioration of positive symptoms and EPS and improvement in attention and working memory performance of schizophrenia and schizoaffective disorder patients. Further double-blind controlled studies are needed to investigate the clinical benefit of pregnenolone augmentation.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00174889.

摘要

目的

孕烯醇酮（PREG）和脱氢表雄酮（DHEA）据报道对神经元兴奋性、突触可塑性和应激反应具有调节作用；它们与情绪调节和认知表现有关。我们研究了 PREG 和 DHEA 对精神病症状和认知功能的影响，作为对慢性精神分裂症或分裂情感障碍患者正在进行的抗精神病治疗的附加治疗。

方法

这是一项为期 8 周、双盲、随机、安慰剂对照、2 中心的研究，比较了 30mg/d 的 PREG（PREG-30）、200mg/d 的 PREG（PREG-200）、400mg/d 的 DHEA 和安慰剂作为 58 例慢性精神分裂症或分裂情感障碍患者（DSM-IV）的辅助治疗。数据收集于 2005 年 2 月至 2007 年 6 月。主要通过临床总体印象-疾病严重程度量表和阳性和阴性综合征量表评估疗效，评估指标为症状和神经认知变化、功能和耐受性。对完成 8 周治疗的 44 例患者和 14 例未完成治疗的患者进行了分析。

结果

与接受安慰剂的患者相比，接受 PREG-30 治疗的患者阳性症状评分和锥体外系副作用（EPS）显著降低，注意力和工作记忆表现改善，而接受 PREG-200 治疗的患者在研究期间的各项研究结果变量评分上无差异。接受安慰剂和 PREG-30 治疗的患者的一般精神病严重程度和一般功能改善程度大于接受 DHEA 治疗的患者，而接受 DHEA 治疗的患者的 EPS 改善程度大于接受安慰剂的患者。任何治疗均未显著改善阴性症状和静坐不能。PREG 和 DHEA 的给药均耐受良好。