Keck Paul E
Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267 0559, USA.
Bipolar Disord. 2005;7 Suppl 4:34-40. doi: 10.1111/j.1399-5618.2005.00213.x.
Bipolar depression, the most common phase of bipolar disorder, causes significant morbidity and mortality. Traditional drugs such as lithium, lamotrigine or antidepressants each offer some clinical efficacy; however, efficacy can be limited and side effects are sometimes problematic. Thus there is a major unmet need for effective, well-tolerated agents for the treatment of bipolar depression. The atypical antipsychotics, with their proven efficacy against manic symptoms, are emerging as candidates for use against the depressive phase of bipolar disorder. Several studies have shown that some atypicals improve depressive symptoms in mixed episodes in patients with bipolar disorder; however, few studies have been performed in patients specifically with bipolar depressive episodes. In a randomized, placebo-controlled trial in patients with acute bipolar I depression, olanzapine monotherapy and an olanzapine-fluoxetine combination significantly improved Montgomery-Asberg Depression Rating Scale (MADRS) total scores compared with placebo (p < 0.001) with corresponding effect sizes (improvement of active treatment over placebo divided by pooled standard deviation) of 0.32 and 0.68, respectively. Importantly, there were no significant differences in rates of switch into mania among the three groups. Recent results from an 8-week, randomized placebo-controlled trial in patients with bipolar I and II disorder who were experiencing a bipolar depressive episode showed that quetiapine (300 and 600 mg/day) had significantly greater efficacy compared with placebo in improving the core symptoms of depression, including suicidal thoughts. Quetiapine significantly improved MADRS total scores compared with placebo (p < 0.001); effect sizes (improvement of quetiapine over placebo divided by pooled standard deviation) of 0.66 and 0.80 for 300 and 600 mg/day quetiapine, respectively, were observed. Both doses of quetiapine significantly improved symptoms of anxiety, sleep quality and global quality of life (all, p < 0.001 versus placebo). These initial findings suggest that atypical antipsychotics may prove to be important future treatments for patients with bipolar depression.
双相抑郁是双相情感障碍最常见的阶段，会导致显著的发病和死亡。传统药物如锂盐、拉莫三嗪或抗抑郁药都有一定的临床疗效；然而，疗效可能有限，且副作用有时会成为问题。因此，对于治疗双相抑郁的有效且耐受性良好的药物存在重大未满足需求。非典型抗精神病药物已被证明对躁狂症状有效，正逐渐成为治疗双相情感障碍抑郁期的候选药物。多项研究表明，一些非典型抗精神病药物可改善双相情感障碍患者混合发作时的抑郁症状；然而，针对单纯双相抑郁发作患者的研究较少。在一项针对急性双相I型抑郁患者的随机、安慰剂对照试验中，与安慰剂相比，奥氮平单药治疗及奥氮平-氟西汀联合治疗显著改善了蒙哥马利-艾斯伯格抑郁量表（MADRS）总分（p < 0.001），相应的效应量（活性治疗组相对于安慰剂组的改善程度除以合并标准差）分别为0.32和0.68。重要的是，三组之间转为躁狂的发生率没有显著差异。一项针对双相I型和II型障碍且正经历双相抑郁发作患者的为期8周的随机安慰剂对照试验的最新结果显示，喹硫平（300和600毫克/天）在改善抑郁核心症状（包括自杀念头）方面与安慰剂相比具有显著更高的疗效。与安慰剂相比，喹硫平显著改善了MADRS总分（p < 0.001）；观察到300毫克/天和600毫克/天喹硫平的效应量（喹硫平相对于安慰剂的改善程度除以合并标准差）分别为0.66和0.80。两种剂量的喹硫平均显著改善了焦虑症状、睡眠质量和总体生活质量（所有指标，与安慰剂相比p < 0.001）。这些初步发现表明，非典型抗精神病药物可能会成为未来治疗双相抑郁患者的重要药物。
