Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; Sierra Pacific Mental Illness Research Education and Clinical Centers, Palo Alto VA Health Care System, Palo Alto, CA, USA.
J Affect Disord. 2014 Dec;169 Suppl 1:S24-33. doi: 10.1016/S0165-0327(14)70006-0.
Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments.
Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-analyses, we assessed the number needed to treat (NNT) for response and the number needed to harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.
The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials.
NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies.
For acute bipolar depression, older approved treatments may have utility in high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug development needs to focus on not only efficacy but also on tolerability.
双相情感障碍的抑郁发作比躁狂发作更为普遍，但治疗方法的证据却较少。
我们使用多中心、随机、双盲、安慰剂对照试验和荟萃分析的数据，评估了针对老年和新型急性双相情感障碍治疗的反应所需的治疗人数（NNT）和所选副作用所需的危害人数（NNH）。
两种已获美国食品药品监督管理局批准的治疗双相情感障碍的老药，奥氮平-氟西汀合剂（OFC）和喹硫平（QTP）单药治疗，均有效（OFC 的反应 NNT=4，QTP 的 NNT=6），但同样可能产生危害（OFC 的体重增加 NNH=6；QTP 的镇静/嗜睡 NNH=5）。常用的未经批准的药物（拉莫三嗪单药治疗和辅助抗抑郁药）往往具有良好的耐受性（NNH 为两位数），尽管这是以疗效不足为代价的（拉莫三嗪的反应 NNT=12，辅助抗抑郁药的 NNT=29）。相比之下，新批准的药物鲁拉西酮不仅有效（单药治疗的反应 NNT=5，辅助治疗的 NNT=7），而且具有更好的耐受性（单药治疗的静坐不能 NNH=15，辅助治疗的恶心 NNH=16）。尽管辅助阿莫达非尼似乎具有良好的耐受性，但它在双相情感障碍中的疗效在随机对照试验中并未得到一致证明。
NNT 和 NNH 是分类指标；仅评估了部分 NNH；疗效（而非有效性）研究的适用性有限。
对于急性双相情感障碍，较老的已批准治疗方法在紧急情况下可能有用，而拉莫三嗪和抗抑郁药在非紧急情况下可能有用。新批准的鲁拉西酮最终可能在各种情况下都有用。新药开发不仅需要关注疗效，还需要关注耐受性。
