BackgroundFour medications are FDA approved for bipolar depression: lurasidone (LUR), cariprazine (CAR), quetiapine IR & XR (QUE), and olanzapine-fluoxetine combination (OFC). Indirect comparisons for efficacy using Number Needed to Treat (NNT) and for tolerability using Number Needed to Harm (NNH) can be useful clinical benchmarks to aid treatment decisions. Benefit and risk may also be examined using the Likelihood to be Helped or Harmed (LHH). In this post-hoc analysis, we examined the benefit-risk ratio of the four treatments using LHH.MethodIndividual and pooled monotherapy data from short-term clinical registration trials of patients with bipolar depression were assessed for LUR, CAR, pooled QUE (300 and 600 mg), and pooled OFC (considered as monotherapy for this study at fixed doses of 6/25, 6/50, 12/50 mg) data. NNT estimates were calculated using the proportions of MADRS responders (defined as ≥ 50% improvement at study endpoint) and MADRS remitters (defined as a score of ≤ 10 [for LUR and CAR] and ≤ 12 [for QUE and OFC]) at study endpoint. NNH data were calculated for the proportions of patients who discontinued due to an adverse event (AE) and for individual AEs commonly associated with each treatment. LHH was calculated as the ratio of NNH/NNT to determine the benefit-risk ratio.ResultsThe NNT estimates for response vs. placebo were: 5 for both LUR 20–60 mg and 80–120 mg; 10 for both CAR 1.5 mg and 3.0 mg; 6 for QUE; and 4 for OFC. The NNTs for remission vs placebo were: 7 for LUR 20–60 mg and 9 for LUR 80–120 mg; 10 for CAR 1.5 mg and 13 for CAR 3.0 mg; 6 for QUE; and 5 for OFC. The NNH estimates for discontinuations due to AEs were: 642 for LUR 20–60 mg and −151 for LUR 80–120 mg; 298 for CAR 1.5 mg and 31 for CAR 3.0 mg; 10 for QUE; and −37 for OFC. NNH values that were negative were assigned a value of 1000 to permit LHH to be calculated. The LHHs for response vs discontinuation due to an AE were: 128.4 for LUR 20–60 mg and 200 for LUR 80–120 mg; 29.8 for CAR 1.5 mg and 3.1 for CAR 3.0 mg; 1.7 for QUE; and 250 for OFC. The LHHs for response vs akathisia were: 3.6 for LUR 20–60 mg and 2.4 for LUR 80–120 mg; 3.6 for CAR 1.5 mg and 1.3 for CAR 3.0 mg; 34 for QUE; and not available (NA) for OFC. The LHHs for response vs EPS were: 8 for LUR 20–60 mg and 3.2 for LUR 80–120 mg; 5 for CAR 1.5 mg and 2.5 for CAR 3.0 mg; NA for QUE; and NA for OFC. The LHH for response vs weight gain was 5.8 for LUR 20–60 mg and 1110 for LUR 80–120 mg; 5 for both doses of CAR; 2.7 for QUE; and 1.5 for OFC.ConclusionsLHH can illustrate the trade-offs regarding potential benefits versus potential harms. Across a variety of measures, the lower-dose groups for both LUR and CAR generally evidenced a better benefit-risk profile than the higher-dose groups. While quetiapine and OFC demonstrated robust efficacy, their reduced tolerability resulted in a more marginal benefit-risk ratio for some of the outcomes.FundingSunovion Pharmaceuticals Inc.

中文翻译：

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使用受帮助或受伤害的可能性 (LHH) 分析评估批准的双相抑郁症治疗的效益风险比

背景 FDA 批准了四种治疗双相抑郁症的药物：鲁拉西酮 (LUR)、卡利拉嗪 (CAR)、喹硫平 IR & XR (QUE) 和奥氮平-氟西汀组合 (OFC)。使用需要治疗的数量 (NNT) 对疗效进行间接比较，使用需要伤害的数量 (NNH) 对耐受性进行间接比较，可以作为有助于治疗决策的有用临床基准。利益和风险也可以使用被帮助或伤害的可能性 (LHH) 来检查。在这项事后分析中，我们使用 LHH 检查了四种治疗方法的效益风险比。方法对双相抑郁症患者的短期临床注册试验的个体和汇总单药治疗数据进行了 LUR、CAR、汇总 QUE（300 和600 mg）和汇总的 OFC（被认为是本研究的单一疗法，固定剂量为 6/25、6/50、12/50 mg）数据。NNT 估计值是使用研究中 MADRS 响应者（定义为研究终点改善 ≥ 50%）和 MADRS 缓解者（定义为分数≤10 [对于 LUR 和 CAR] 和≤ 12 [对于 QUE 和 OFC]）的比例计算的端点。NNH 数据针对因不良事件 (AE) 而停药的患者比例以及通常与每种治疗相关的个体 AE 进行计算。LHH 被计算为 NNH/NNT 的比率以确定收益-风险比。结果 NNT 对反应与安慰剂的估计为：LUR 20-60 mg 和 80-120 mg 均为 5；CAR 1.5 mg 和 3.0 mg 均为 10；6 为 QUE；和 4 个用于 OFC。缓解与安慰剂的 NNT 为：LUR 20-60 mg 为 7，LUR 80-120 mg 为 9；CAR 1.5 mg 为 10，CAR 3.0 mg 为 13；6 为 QUE；和 5 个用于 OFC。因 AE 导致的停药的 NNH 估计值为：LUR 20–60 mg 为 642，LUR 80–120 mg 为 -151；CAR 1.5 mg 为 298，CAR 3.0 mg 为 31；10 为 QUE；OFC 为 -37。为负的 NNH 值被指定为 1000 以允许计算 LHH。因 AE 引起的反应与停药的 LHH 分别为：LUR 20-60 mg 为 128.4，LUR 80-120 mg 为 200；CAR 1.5 mg 为 29.8，CAR 3.0 mg 为 3.1；1.7 为 QUE；OFC 为 250。反应与静坐不能的 LHH 分别为：LUR 20-60 mg 为 3.6，LUR 80-120 mg 为 2.4；CAR 1.5 mg 为 3.6，CAR 3.0 mg 为 1.3；34 为 QUE；并且不适用于 OFC。响应与 EPS 的 LHH 为：LUR 20-60 mg 为 8，LUR 80-120 mg 为 3.2；CAR 1.5 mg 为 5，CAR 3.0 mg 为 2.5；不适用于 QUE；和 NA 用于 OFC。LUR 20-60 mg 的反应与体重增加的 LHH 为 5.8，LUR 80-120 mg 的 LHH 为 1110；两种剂量的 CAR 均为 5；2.7 用于 QUE；和 1。5 for OFC. 结论LHH 可以说明潜在利益与潜在危害之间的权衡。在各种测量中，LUR 和 CAR 的低剂量组通常证明比高剂量组更好的收益-风险特征。虽然喹硫平和 OFC 显示出强大的疗效，但它们降低的耐受性导致某些结果的边际效益风险比更高。 资金 Sunovion Pharmaceuticals Inc.