The Monash Alfred Psychiatry Research Centre, The Alfred and Monash University Central Clinical School, Monash University, Melbourne, Australia.
IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.
Mol Psychiatry. 2015 Jun;20(6):695-702. doi: 10.1038/mp.2014.33. Epub 2014 Apr 15.
Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean = 35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.
许多患有精神分裂症的女性尽管采用了最佳的现有治疗方法，但仍存在症状。虽然之前的研究表明，雌激素辅助治疗可能有效，但在临床应用之前需要进行大规模的临床试验。这项研究是首例针对治疗抵抗性精神分裂症女性的大规模随机对照试验。这项雌二醇贴剂确证试验是一项 8 周、三臂、双盲、随机对照试验，于 2006 年至 2011 年进行。183 名女性参与者年龄在 18 至 45 岁之间（平均年龄 35 岁），患有精神分裂症或分裂情感障碍，且持续存在精神病症状（阳性和阴性综合征量表，PANSS 评分>60），尽管抗精神病药物的稳定剂量至少已使用 4 周。平均病程超过 10 年。参与者接受了经皮雌二醇 200 μg、经皮雌二醇 100 μg 或相同的安慰剂贴片。对于完成研究的 180 名女性，预先设定的结果测量是在基线和第 7、14、28 和 56 天测量的 PANSS 评分变化。认知功能在基线和第 56 天使用重复神经心理状态测试进行评估。数据使用潜在增长曲线模型进行分析。与安慰剂组相比，两个雌二醇组的 PANSS 阳性、一般和总症状都有更大程度的降低（P<0.01），而 200 μg 雌二醇组的效果比 100 μg 雌二醇组更显著。雌二醇 200 μg 治疗组的 PANSS 阳性症状子量表的效果最大（效应大小 0.44，P<0.01）。这项研究表明，雌二醇是治疗抵抗性精神分裂症女性的一种有效且具有临床意义的辅助治疗方法，尤其对阳性症状有效。
