1 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
3 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
CNS Spectr. 2013 Dec;18 Suppl 1:4-20; quiz 21. doi: 10.1017/S1092852913000746. Epub 2013 Nov 15.
OBJECTIVES/INTRODUCTION: Herein we review the evidence supporting Food and Drug Administration (FDA) approved and emerging treatments for bipolar depression.
A PubMed search of all English-language articles published up to July 2013 was conducted. The search terms were quetiapine, olanzapine-fluoxetine, olanzapine, lurasidone, ketamine, modafinil/armodafinil, and lamotrigine. The search was augmented with a manual review of relevant article reference lists, as well as posters presented at national and international meetings. Articles selected for review were based on the adequacy of sample size, the use of standardized diagnostic instruments, validated assessment measures, and overall manuscript quality.
Olanzapine-fluoxetine combination (OFC), quetiapine, and lurasidone are FDA-approved for the acute treatment of bipolar depression. Lurasidone is the most recently approved agent for bipolar depression. Olanzapine-fluoxetine combination and quetiapine are approved as single modality therapies while lurasidone is approved as a monotherapy and as an adjunct to lithium or divalproex. The overall effect size of the 3 treatments in mitigating depressive symptoms is similar. Clinically significant weight gain and metabolic disruption as well as sedation are significant limitations of OFC and quetiapine. The minimal propensity for weight gain as well as the metabolic neutrality of lurasidone in the bipolar population is a clinically significant advantage. Evidence also supports lamotrigine with compelling evidence as an adjunct to lithium and in recurrence prevention paradigm; suggested evidence also exists for ketamine and modafinil/armodafinil; notwithstanding, these treatments remain investigational.
Relatively few agents are FDA-approved for bipolar depression. The selection and sequencing of agents in bipolar depression should give primacy to those agents that are FDA-approved. Further refinement of the selection process will need to pay careful attention to the relative hazards of weight gain and metabolic disruption in this highly susceptible population. Other agents with differential mechanisms (eg, ketamine) offer a promising alternative in bipolar depression.
目的/引言：本文回顾了支持美国食品和药物管理局（FDA）批准和新兴治疗双相情感障碍的证据。
对截至 2013 年 7 月所有已发表的英文文章进行了 PubMed 检索。检索词为喹硫平、奥氮平-氟西汀、奥氮平、鲁拉西酮、氯胺酮、莫达非尼/阿莫达非尼和拉莫三嗪。通过手动审查相关文章的参考文献列表以及在国内和国际会议上提交的海报，对检索进行了补充。选择进行审查的文章是基于样本量是否充足、是否使用标准化诊断工具、使用验证评估措施以及总体手稿质量。
奥氮平-氟西汀联合（OFC）、喹硫平和鲁拉西酮被 FDA 批准用于急性双相情感障碍治疗。鲁拉西酮是最近批准用于双相情感障碍的药物。奥氮平-氟西汀联合和喹硫平被批准为单一疗法，而鲁拉西酮被批准为单药治疗以及锂或丙戊酸钠的辅助治疗。3 种治疗方法缓解抑郁症状的总体效果大小相似。OFC 和喹硫平的显著限制是临床显著的体重增加和代谢紊乱以及镇静。鲁拉西酮在双相人群中增加体重的可能性最小，以及代谢中性是一个显著的临床优势。证据还支持拉莫三嗪与锂联合使用，并在预防复发模式中具有强烈的辅助作用；也有证据表明氯胺酮和莫达非尼/阿莫达非尼也有作用；尽管如此，这些治疗方法仍在研究中。
相对较少的药物获得 FDA 批准用于双相情感障碍。在双相情感障碍中选择和使用药物应优先考虑那些获得 FDA 批准的药物。在这个高度敏感的人群中，需要仔细注意体重增加和代谢紊乱的相对风险，进一步完善选择过程。具有不同机制（如氯胺酮）的其他药物为双相情感障碍提供了有希望的替代选择。
