A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression
A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression
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DOI：
10.1038/npp.2014.138
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发表时间：
2014-11-01
影响因子：
7.6
通讯作者：
Holmes, Traci
中科院分区：
文献类型：
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作者：
Brown, E. Sherwood;Park, John;Holmes, Traci
双相情感障碍（BPD）抑郁症的治疗具有挑战性。因此，需要额外的药物选择。在目前的报告中，研究了神经类固醇孕烯醇酮对BPD抑郁症状的影响。成人（n = 80）患有BPD，抑郁情绪状态，随机分为孕烯醇酮组（滴定至500 mg/天）或安慰剂组，作为附加治疗，为期12周。结果测量包括17项汉密尔顿抑郁评定量表（HRSD）、抑郁症状自述量表（IDS-SR）、汉密尔顿焦虑评定量表（HRSA）和青年躁狂症评定量表（YMRS）。在基线和第12周评估血清神经类固醇水平。使用混合模型ANCOVA分析数据，其中治疗分配的间因子、访问的内因子（重复）、基线值以及年龄和性别为协变量。在基线后至少进行一次访问的参与者（n = 73）中，观察到HRSD （F(5288) = 2.61, p = 0.025）的周交互作用显著，但没有观察到IDS-SR。根据IDS-SR (chi（2)(1) = 3.99, p = 0.046）评估，孕烯醇酮组的抑郁缓解率（61%）高于安慰剂组（37%），但HRSD没有。孕烯醇酮组观察到基线至退出时神经类固醇水平的大变化，而安慰剂组没有。孕烯醇酮组HRSA与异孕烯醇酮（r(22) = 0.43, p = 0.036）、孕烯醇酮（r(22) = 0.48, p = 0.019）水平变化呈负相关。孕烯醇酮耐受性良好。结果表明孕烯醇酮可以改善BPD患者的抑郁症状，并且可以安全使用。
Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n = 80) with BPD, depressed mood state, were randomized to pregnenolone (titrated to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n = 73), a significant treatment by week interaction for the HRSD (F(5,288) = 2.61, p = 0.025), but not IDS-SR, was observed. Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (chi(2)(1) = 3.99, p = 0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels were observed in the pregnenolone group but not in the placebo group. In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22) = 0.43, p = 0.036) and pregNANolone (r(22) = 0.48, p = 0.019) levels. Pregnenolone was well tolerated. The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered.