Deshauer Dorian, Moher David, Fergusson Dean, Moher Ester, Sampson Margaret, Grimshaw Jeremy
Department of Psychiatry, University of Ottawa, Ottawa, Ont.
CMAJ. 2008 May 6;178(10):1293-301. doi: 10.1503/cmaj.071068.
Selective serotonin reuptake inhibitors are increasingly used in the long-term treatment of depression. Much of the supporting evidence about the effects of these drugs comes from discontinuation trials, a variant of randomized controlled trials whose design is problematic to interpret. We conducted a systematic review to examine the efficacy and acceptability of long-term therapy with selective serotonin reuptake inhibitors relative to placebo in the treatment of unipolar depression.
We identified placebo-controlled randomized trials with a treatment duration of at least 6 months by searching MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to update a recently published systematic review. Efficacy was defined in terms of response to treatment (50% improvement in depression score relative to baseline) and remission (score of 7 or below on the Hamilton rating scale for depression). Key secondary outcomes included quality of life, return to work, need for additional treatment and self-harm. Overall acceptability was defined in terms of dropouts for any reason over a course of treatment.
Of the 2693 records identified initially, we included 6 randomized controlled trials that met our eligibility criteria. These studies had a moderate risk of bias, had assigned a total of 1299 participants with depression to either treatment or placebo and had followed both groups for 6-8 months. We observed statistically significant improvements in response to treatment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.12-2.48), but not in remission (OR 1.46, 95% CI 0.92-2.32) or acceptability (OR 0.87, 95% CI 0.67-1.14). The effects appeared greater among patients without comorbidities.
There is a lack of classic randomized controlled trials of serotonin reuptake inhibitors lasting more than 1 year for the treatment of depression. The results of our systematic review support current recommendations for 6-8 months of antidepressant treatment following initial recovery but provide no guidance for longer treatment.
选择性5-羟色胺再摄取抑制剂越来越多地用于抑郁症的长期治疗。关于这些药物疗效的许多支持性证据来自撤药试验，这是随机对照试验的一种变体，其设计在解释上存在问题。我们进行了一项系统评价，以研究选择性5-羟色胺再摄取抑制剂相对于安慰剂在治疗单相抑郁症中的长期治疗效果和可接受性。
我们通过检索MEDLINE、EMBASE和Cochrane对照试验中央注册库来识别治疗持续时间至少为6个月的安慰剂对照随机试验，以更新最近发表的系统评价。疗效根据治疗反应（抑郁评分相对于基线改善50%）和缓解情况（汉密尔顿抑郁评定量表评分7分或以下）来定义。关键的次要结局包括生活质量、重返工作岗位、额外治疗需求和自我伤害。总体可接受性根据治疗过程中因任何原因退出的情况来定义。
在最初识别的2693条记录中，我们纳入了6项符合我们纳入标准的随机对照试验。这些研究存在中度偏倚风险，共将1299名抑郁症患者分配至治疗组或安慰剂组，并对两组进行了6-8个月的随访。我们观察到治疗反应有统计学显著改善（优势比[OR]1.66，95%置信区间[CI]1.12-2.48），但缓解情况（OR 1.46，95%CI 0.92-2.32）或可接受性（OR 0.87，95%CI 0.67-1.14）无统计学显著改善。在无合并症的患者中，效果似乎更大。
缺乏持续时间超过1年的用于治疗抑郁症的5-羟色胺再摄取抑制剂的经典随机对照试验。我们系统评价的结果支持初始康复后进行6-8个月抗抑郁治疗的当前建议，但对于更长时间的治疗没有提供指导。
