目的:比较第二代抗精神病药(SGA)和情绪稳定剂(MS)在患有双相情感障碍1型(BD-I)躁狂/混合发作的年轻人中的应用。
方法:系统PubMed/Embase/PsycInfo文献检索至2023年12月31日,在年龄≤18岁的BD-I躁狂/混合发作患者中进行SGA或MS的随机试验。网络荟萃分析,比较有关躁狂症状和躁狂反应的治疗方法(共同主要结果),和次要疗效和耐受性结果。
结果:18项研究(n=2844,平均年龄=11.74,女性=48.0%,平均研究持续时间=5.4周),比较六个SGA(阿立哌唑,阿塞那平,奥氮平,喹硫平,利培酮,齐拉西酮)和四个MS(锂,奥卡西平,托吡酯,丙戊酸盐)进行荟萃分析。所有六个SGA在减少躁狂症状方面优于安慰剂,包括利培酮(SMD=-1.18,95CI=-0.92;-1.45,CINeMA=中等置信度),奥氮平(SMD=-0.77,95CI=-0.36;-1.18,低置信度),阿立哌唑(SMD=-0.67,95CI=-0.33;-1.01,中等置信度),喹硫平(SMD=-0.60,95CI=-0.32,-0.87,高置信度),阿塞那平(SMD=-0.54,95CI=-0.19;-0.89,中等置信度),和齐拉西酮(SMD=-0.43,95CI=-0.17-0.70,低置信度),而没有情绪稳定剂优于安慰剂。关于躁狂症的反应,利培酮(RR=2.58,95CI=1.88;3.54,低置信度),奥氮平(RR=2.42,95CI=1.33-3.54,置信度非常低),阿立哌唑(RR=2.05,95CI=1.44-2.92,低置信度),喹硫平(RR=1.89,95CI=1.45-2.47,中等置信度),阿塞那平(RR=1.81,95CI=1.28-2.55,置信度非常低)和锂(RR=1.35,95CI=1.00;1.83,p值=0.049,置信度非常低)优于安慰剂,与安慰剂相比,其他MS没有优势。个别地,利培酮在减少躁狂症状方面比所有其他比较药物更有效,除了奥氮平和托吡酯,然而,低/非常低的信心,并与催乳素和葡萄糖的增加有关。汇集在一起,SGA在躁狂症状减轻方面优于安慰剂和MS(SMD=-0.68,95CI=-0.86;-0.51和SMD=-0.61,95CI=-0.82;-0.40,中等置信度),和躁狂症反应(RR=1.85,95CI=1.53;2.24和RR=1.65,95CI=1.33-2.04,中度置信度),MS和安慰剂之间没有差异。全因停药的治疗-安慰剂没有显著差异,而锂,与安慰剂相比,齐拉西酮和奥卡西平与更多不良事件相关的退出相关.大多数SGA与更多的镇静有关,体重增加,与安慰剂和MS相比,代谢问题。
结论:在治疗急性躁狂症状方面,SGA比安慰剂和MS更有效,然而,它们的使用必须仔细权衡重要的副作用。
OBJECTIVE: To compare second-generation antipsychotics (SGAs) and mood stabilizers (MSs) in youth with a bipolar disorder type I (BD-I) manic/mixed episode.
METHODS: A systematic PubMed/Embase/PsycInfo literature search until December 31, 2023, for randomized trials of SGAs or MSs in patients ≤18 years of age with BD-I manic/mixed episode was conducted. The study included a network meta-analysis comparing treatments regarding mania symptoms and mania response (co-primary outcomes), and secondary efficacy and tolerability outcomes.
RESULTS: Eighteen studies (n = 2844, mean age = 11.74, female participants = 48.0%, mean study duration = 5.4 weeks) comparing 6 SGAs (aripiprazole, asenapine, olanzapine, quetiapine, risperidone, and ziprasidone) and 4 MSs (lithium, oxcarbazepine, topiramate, and valproate) were meta-analyzed. All 6 SGAs outperformed placebo in reducing manic symptomatology, including risperidone (standardized mean difference [SMD] = -1.18, 95% CI = -0.92, -1.45, Confidence in Network Meta-Analysis [CINeMA] = moderate confidence), olanzapine (SMD = -0.77, 95% CI = -0.36, -1.18, low confidence), aripiprazole (SMD = -0.67, 95% CI = -0.33, -1.01, moderate confidence), quetiapine (SMD = -0.60, 95% CI = -0.32, -0.87, high confidence), asenapine (SMD = -0.54, 95% CI = -0.19, -0.89, moderate confidence), and ziprasidone (SMD = -0.43, 95% CI = -0.17, 0.70, low confidence), whereas no mood stabilizer outperformed placebo. Concerning mania response, risperidone (Risk ratio [RR] = 2.58, 95% CI = 1.88, 3.54, low confidence), olanzapine (RR = 2.42, 95% CI = 1.33, 3.54, very low confidence), aripiprazole (RR = 2.05, 95% CI = 1.44, 2.92, low confidence), quetiapine (RR = 1.89, 95% CI = 1.45n 2.47, moderate confidence), asenapine (RR = 1.81, 95% CI = 1.28, 2.55, very low confidence) and lithium (RR = 1.35, 95% CI = 1.00, 1.83, p = .049, very low confidence) outperformed placebo, without superiority of other MSs vs placebo. Individually, risperidone was more efficacious in reducing manic symptomatology than all other comparators, except olanzapine and topiramate, yet with low/very low confidence, and was associated with increased prolactin and glucose. Pooled together, SGAs outperformed both placebo and MSs for mania symptom reduction (SMD = -0.68, 95% CI = -0.86, -0.51 and SMD = -0.61, 95% CI = -0.82, -0.40, moderate confidence), and mania response (RR = 1.85, 95% CI = 1.53, 2.24 and RR = 1.65, 95% CI = 1.33, 2.04, moderate confidence) without differences between MSs and placebo. There were no significant treatment-placebo differences for all-cause discontinuation, whereas lithium, ziprasidone, and oxcarbazepine were associated with more adverse event-related drop-outs than placebo. Most SGAs were associated with more sedation, weight gain, and metabolic issues vs placebo and MSs.
CONCLUSIONS: SGAs were more efficacious than placebo and MSs in treating acute mania symptoms, however, their use must be carefully weighed against important side effects.