Eden Evins A, Demopulos Christina, Nierenberg Andrew, Culhane Melissa A, Eisner Lori, Sachs Gary
Department of Psychiatry of the Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Bipolar Disord. 2006 Feb;8(1):75-80. doi: 10.1111/j.1399-5618.2006.00243.x.
Because there is a high rate of partial response to standard thymoleptic medication, novel augmentation strategies for treatment-resistant bipolar disorder are needed. In an open trial, donepezil augmentation was associated with improvement in manic symptoms in 9 of 11 subjects.
We conducted a 6-week, double-blind, placebo-controlled trial of donepezil for treatment-resistant bipolar mania. Eligible subjects had a Young Mania Rating Scale (YMRS) score of at least 15 despite two or more weeks of proven therapeutic levels of lithium or valproate. Subjects who completed the trial were eligible for an 8-week open trial of donepezil. Subjects were started on donepezil 5 mg/day and were eligible for dose increase to 10 mg/day after 4 weeks.
Twelve subjects were enrolled. Eleven subjects received at least 1 week of study medication and were included in the analysis. No subjects in the donepezil group (0/6) and 60% (3/5) in the placebo group met response criteria of >30% reduction in YMRS score (Fisher's Exact p = 0.061). YMRS scores were higher at trial endpoint in the donepezil group 20.17 (3.66) compared with the placebo group [11.20 (4.60), Z = -2.476, p = 0.01]. There were no differences at trial endpoint in Hamilton Rating Scale for Depression (HAM-D) or Brief Psychiatric Rating Scale (BPRS) scores in either the intent-to-treat or the completer analyses.
Donepezil does not appear to be an effective adjunctive treatment for refractory manic symptoms. The strength of the conclusion of this trial is limited by the possibility of a false-negative result due to the small sample.
由于对标准心境稳定剂药物的部分缓解率较高，因此需要针对难治性双相情感障碍的新型增效策略。在一项开放性试验中，11名受试者中有9名在使用多奈哌齐增效治疗后躁狂症状得到改善。
我们进行了一项为期6周的双盲、安慰剂对照试验，以评估多奈哌齐治疗难治性双相躁狂的疗效。符合条件的受试者尽管已接受锂盐或丙戊酸盐治疗达有效治疗水平两周以上，但杨氏躁狂量表（YMRS）评分仍至少为15分。完成试验的受试者有资格参加为期8周的多奈哌齐开放性试验。受试者起始剂量为多奈哌齐5毫克/天，4周后可将剂量增加至10毫克/天。
共纳入12名受试者。11名受试者接受了至少1周的研究药物治疗，并纳入分析。多奈哌齐组无受试者（0/6）达到YMRS评分降低>30%的反应标准，而安慰剂组有60%（3/5）的受试者达到该标准（Fisher精确检验p = 0.061）。试验终点时，多奈哌齐组的YMRS评分更高，为20.17（3.66），而安慰剂组为[11.20（4.60），Z = -2.476，p = 0.01]。在意向性分析或完成者分析中，试验终点时汉密尔顿抑郁量表（HAM-D）或简明精神病评定量表（BPRS）评分在两组之间均无差异。
多奈哌齐似乎不是治疗难治性躁狂症状的有效辅助治疗药物。由于样本量较小，该试验结论存在假阴性结果的可能性，因此结论的力度有限。
