Bartoli Francesco, Dell'Osso Bernardo, Crocamo Cristina, Fiorillo Andrea, Ketter Terence A, Suppes Trisha, Clerici Massimo, Carrà Giuseppe
Department of Medicine and Surgery, University of Milano Bicocca, Milano, Italy.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford School of Medicine, Stanford, CA, USA; Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
J Psychiatr Res. 2017 May;88:38-46. doi: 10.1016/j.jpsychires.2016.12.021. Epub 2017 Jan 1.
The aim of this systematic review and meta-analysis was testing whether low versus high doses of second-generation antipsychotics (SGAs) are associated with different clinical benefits and harms for the acute treatment of bipolar depression. We included clinical trials comparing different doses of the same SGA monotherapy for bipolar depression. SGAs defined daily doses were used to define high and low doses. Clinical benefit outcomes included improvement, response and remission rates on Montgomery-Asberg Depression Rating Scale. Clinical harm outcomes included all-cause and adverse effect-related discontinuation rates. Data from seven clinical trials testing high and low doses of quetiapine (4 trials), cariprazine, lurasidone, and ziprasidone (1 trial each), showed no differences between lower and higher doses of selected SGAs on improvement, response and remission rates, without significant heterogeneity across studies (I = 0%). Subgroup analyses based on single SGAs confirmed the clinical benefit comparability between low and high doses. However, clinical harm favorable differences for low doses on all-cause (p = 0.01) and adverse effects-related discontinuation (p = 0.001) were found. In sum, this meta-analysis showed that, although no benefits were found in terms of symptoms improvement, response and remission rates, there were clear disadvantages in prescribing higher rather than lower doses of selected SGAs. The uniform methodological strength of studies increases confidence in our findings. These data need to be integrated with individual patient characteristics (e.g., clinical urgency and adverse effect sensitivity) to optimize management of acute bipolar depression.
本系统评价和荟萃分析的目的是检验第二代抗精神病药物（SGA）低剂量与高剂量用于双相抑郁急性治疗时，其临床获益和危害是否存在差异。我们纳入了比较相同SGA单药不同剂量治疗双相抑郁的临床试验。根据SGA的定义日剂量来界定高剂量和低剂量。临床获益结局包括蒙哥马利-艾斯伯格抑郁量表的改善、反应和缓解率。临床危害结局包括全因停药率和不良反应相关停药率。7项分别测试喹硫平高、低剂量（4项试验）、卡立普唑、鲁拉西酮和齐拉西酮（各1项试验）的临床试验数据显示，所选SGA的低剂量和高剂量在改善、反应和缓解率方面无差异，各研究间无显著异质性（I² = 0%）。基于单一SGA的亚组分析证实了低剂量和高剂量在临床获益方面具有可比性。然而，发现低剂量在全因（p = 0.01）和不良反应相关停药（p = 0.001）方面具有临床危害优势差异。总之，本荟萃分析表明，虽然在症状改善、反应和缓解率方面未发现益处，但在开具所选SGA的高剂量而非低剂量时存在明显劣势。研究统一的方法学优势增强了我们对研究结果的信心。这些数据需要与个体患者特征（如临床紧迫性和不良反应敏感性）相结合，以优化双相抑郁急性发作的管理。
