Merck Research Laboratories, Rahway, NJ, USA.
BMC Psychiatry. 2011 Jun 20;11:101. doi: 10.1186/1471-244X-11-101.
Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.
In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ≥4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures.
Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3.
These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.
在两项随机、安慰剂对照、奥氮平对照的临床试验中，阿塞那平在治疗双相 I 型障碍患者急性当前躁狂或混合发作时，显示出优于安慰剂的疗效。我们报告了这些试验中探索性事后分析的结果，这些分析评估了阿塞那平对基线时有显著抑郁症状的这些试验患者的抑郁症状的影响。
在原始试验（A7501004[NCT00159744]、A7501005[NCT00159796]）中，977 名患者被随机分配至灵活剂量舌下含服阿塞那平（第 1 天每日 2 次 10mg；此后每日 2 次 5 或 10mg）、安慰剂或口服奥氮平 5-20mg 每日 1 次，治疗 3 周。根据基线时的抑郁症状，将患者分为以下三种人群：（1）蒙哥马利-阿斯伯格抑郁评定量表（MADRS）总分≥20 分（n=132）；（2）双相障碍临床总体印象-抑郁（CGI-BP-D）量表严重程度评分≥4 分（n=170）；（3）由研究机构筛选的混合发作诊断（n=302）。对于每个人群，使用抑郁症状测量的从基线的最小二乘均数变化，分别比较阿塞那平和奥氮平与安慰剂的疗效。
在所有人群中，阿塞那平组在第 7 天和第 21 天的 MADRS 总分较安慰剂组下降更为显著；奥氮平组与安慰剂组之间的差异无统计学意义。在所有分类中，阿塞那平组在第 7 天，人群 1 中在第 21 天的 CGI-BP-D 评分下降均显著大于安慰剂组；奥氮平组在第 21 天的人群 1 中，第 7 天的人群 2 和人群 3 中 CGI-BP-D 评分下降均显著大于安慰剂组。
这些事后分析表明，阿塞那平可降低基线时有临床相关抑郁症状的急性躁狂或混合发作的双相 I 型障碍患者的抑郁症状；奥氮平的结果似乎不太一致。需要开展阿塞那平治疗急性双相抑郁患者的对照研究，以确认这些发现的普遍性。
