McGirr Alexander, Vöhringer Paul A, Ghaemi S Nassir, Lam Raymond W, Yatham Lakshmi N
Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
Unidad Tratornos del Animo, Hospital Clinico Universidad de Chile, Santiago, Chile; Millennium Institute for Depression and Personality Resarch, Ministry of Economy, Santiago, Chile; Mood Disorders Program, Tufts University Medical School, Boston, MA, USA.
Lancet Psychiatry. 2016 Dec;3(12):1138-1146. doi: 10.1016/S2215-0366(16)30264-4. Epub 2016 Oct 26.
Although mania and hypomania define bipolar disorder, depressive episodes are more common and impairing, with few proven treatments. Adjunctive therapy with second-generation antidepressants is widely used to treat acute bipolar depression, but their efficacy and safety remain controversial.
In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to Jan 31, 2016, for randomised, double-blind, placebo-controlled trials of second-generation antidepressants adjunctive to a mood stabiliser or an antipsychotic in patients with acute bipolar depression. We extracted data from published reports. The primary outcome was change in clinician-rated depressive symptom score; secondary outcomes were clinical response, clinical remission, treatment-emergent mania or hypomania, and tolerability (using dropout rates as a proxy). We used pooled random-effects models, subgroup comparisons, and meta-regression for analyses. We made subgroup comparisons on the basis of mood stabiliser or antipsychotic treatment and did meta-regression examining trial duration. This study is registered with PROSPERO, number CRD#42015016024.
We identified six trials representing 1383 patients with bipolar depression. Second-generation antidepressants were associated with a small but significant improvement in clinician-rated depressive symptom score (standardised mean differences 0·165 [95% CI 0·051-0·278], p=0·004). However, clinical response and remission rates did not differ significantly between patients receiving adjunctive antidepressants and those receiving placebo (1·158 [0·840-1·597], p=0·371 for clinical response; 1·220 [0·874-1·703], p=0·243 for remission). Acute treatment was not associated with an increased risk of treatment-emergent mania or hypomania (0·926 [0·576-1·491], p=0·753), but 52 week extension periods were associated with an increase in risk (1·774 [1·018-3·091], p=0·043).
Adjunctive second-generation antidepressants are associated with reduced symptoms of acute bipolar depression, but the magnitude of benefit is small because they do not increase clinical response or remission rates. However, these medications should be used only in the short term because prolonged use is associated with an increased risk of treatment-emergent mania or hypomania.
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尽管躁狂和轻躁狂是双相情感障碍的定义性症状，但抑郁发作更为常见且具有损害性，而经证实有效的治疗方法却很少。第二代抗抑郁药辅助治疗被广泛用于治疗急性双相抑郁，但它们的疗效和安全性仍存在争议。
在这项系统评价和荟萃分析中，我们检索了MEDLINE、Embase、Cochrane对照试验中央注册库和ClinicalTrials.gov，检索时间从各数据库建库至2016年1月31日，以查找关于第二代抗抑郁药辅助心境稳定剂或抗精神病药治疗急性双相抑郁患者的随机、双盲、安慰剂对照试验。我们从已发表的报告中提取数据。主要结局是临床医生评定的抑郁症状评分的变化；次要结局是临床反应、临床缓解、治疗中出现的躁狂或轻躁狂以及耐受性（以脱落率作为替代指标）。我们使用汇总随机效应模型、亚组比较和Meta回归进行分析。我们根据心境稳定剂或抗精神病药治疗进行亚组比较，并进行Meta回归以检验试验持续时间。本研究已在国际前瞻性系统评价注册库（PROSPERO）注册，注册号为CRD#42015016024。
我们确定了6项试验，共1383例双相抑郁患者。第二代抗抑郁药与临床医生评定的抑郁症状评分有小幅但显著的改善相关（标准化均数差0.165 [95%CI 0.051 - 0.278]，p = 0.004）。然而，接受辅助抗抑郁药治疗的患者与接受安慰剂治疗的患者在临床反应和缓解率方面没有显著差异（临床反应：1.158 [0.840 - 1.597]，p = 0.371；缓解：1.220 [0.874 - 1.703]，p = 0.243）。急性治疗与治疗中出现躁狂或轻躁狂的风险增加无关（0.926 [0.576 - 1.491]，p = 0.753），但52周的延长期与风险增加相关（1.774 [1.018 - 3.091]，p = 0.043）。
辅助使用第二代抗抑郁药与急性双相抑郁症状减轻相关，但获益程度较小，因为它们并未提高临床反应或缓解率。然而，这些药物仅应短期使用，因为长期使用与治疗中出现躁狂或轻躁狂的风险增加相关。
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