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Treatment of bipolar depression: making sensible decisions

机译：治疗躁郁症：做出明智的决定

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A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/ fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression.
机译：在治疗与躁郁症相关的严重抑郁发作中的主要挑战是将这种疾病与与严重抑郁症相关的严重抑郁发作区分开。前者误认为后者会导致不正确的治疗和不良的后果。经典抗抑郁药，5-羟色胺特异性再摄取抑制剂或5-羟色胺-去甲肾上腺素再摄取抑制剂均未获得监管批准作为治疗双相抑郁症的单一疗法。目前，只有两种批准的双相抑郁症药物治疗方法：奥氮平/氟西汀组合，喹硫平（立即或延长释放）和卢拉西酮（单药治疗或锂或丙戊酸盐辅助治疗）。所有这三种药物具有相似的功效特征，但是在耐受性方面有所不同。治疗所需的数量（NNT）和伤害所需的数量（NNH）可用于量化这些相似和不同之处。这些干预措施相对于安慰剂的缓解和缓解的NNT值分别为4至7和5至7，在其95％置信区间上有重叠。对于奥氮平/氟西汀组合（分别为7和9）以及喹硫平的嗜睡和口干（分别为3和4），自发报告的体重增加和腹泻的不良事件观察到NNH值小于10（相对于安慰剂）。卢拉西酮治疗未观察到NNH值小于10（相对于安慰剂）。对于奥氮平/氟西汀组合，喹硫平，卢拉西酮单药和卢拉西酮联合锂或丙戊酸盐，与基线相比体重至少增加7％的NNH值相对于安慰剂分别为6、16、58和36。个性化的治疗决策将需要考虑每种药物更可能发生的不同潜在不良事件。受到帮助或受到损害的可能性（LHH）的度量标准是NNH与NNT的比率，可以说明选择药物时固有的权衡。注意到用卢拉西酮治疗更有利的LHH。但是，OFC和喹硫平单药治疗仍可在紧急情况下使用，特别是在过去通过这些干预措施已显示出良好疗效的患者，以及临床上迫切需要疗效的患者，可缓解其潜在的耐受性缺陷。就维持疗法而言，喹硫平是唯一可以预防躁狂和抑郁症的药物，其NNT与锂或丙戊酸酯的含量小于10。

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