Molyneaux Emma, Howard Louise M, McGeown Helen R, Karia Amar M, Trevillion Kylee
Health Service and Population Research Department, The Institute of Psychiatry, Psychology & Neuroscience, King's College London, PO31 De Crespigny Park, London, UK, SE5 8AF.
Cochrane Database Syst Rev. 2014 Sep 11;2014(9):CD002018. doi: 10.1002/14651858.CD002018.pub2.
Postnatal depression is a common disorder that can have adverse short- and long-term effects on maternal morbidity, the new infant and the family as a whole. Treatment is often largely by social support and psychological interventions. It is not known whether antidepressants are an effective and safe choice for treatment of this disorder. This review was undertaken to evaluate the effectiveness of different antidepressants and to compare their effectiveness with other forms of treatment, placebo or treatment as usual. It is an update of a review first published in 2001.
To assess the effectiveness of antidepressant drugs in comparison with any other treatment (psychological, psychosocial or pharmacological), placebo or treatment as usual for postnatal depression.
We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialized Register (CCDANCTR) to 11 July 2014. This register contains reports of relevant randomised controlled trials (RCTs) from the following bibliographic databases: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE, (1974 to date) and PsycINFO (1967 to date). We also searched international trial registries and contacted pharmaceutical companies and experts in the field.
We included RCTs of women with depression with onset up to six months postpartum that compared antidepressant treatment (alone or in combination with another treatment) with any other treatment, placebo or treatment as usual.
Two review authors independently extracted data from the trial reports. We requested missing information from investigators wherever possible. We sought data to allow an intention-to-treat analysis. Random effects meta-analyses were conducted to pool data where sufficient comparable studies were identified.
We included six trials with 596 participants in this review. All studies had a randomised controlled parallel group design, with two conducted in the UK, three in the US and one in Israel. Meta-analyses were performed to pool data on response and remission from studies comparing antidepressants with placebo. No meta-analyses could be conducted for other comparisons due to the small number of trials identified.Four studies compared selective serotonin reuptake inhibitors (SSRIs) with placebo (two using sertraline, one using paroxetine and one using fluoxetine; 233 participants in total). In two of these studies both the experimental and placebo groups also received psychological therapy. Pooled risk ratios based on data from three of these studies (146 participants) showed that women randomised to SSRIs had higher rates of response and remission than those randomised to placebo (response: RR 1.43, 95% CI 1.01 to 2.03; remission: RR 1.79, 95% CI 1.08 to 2.98); the fourth study did not report data on response or remission.One study (254 participants) compared antidepressant treatment with treatment as usual (for the first four weeks) followed by listening visits. The study found significantly higher rates of improvement in the antidepressant group than treatment-as-usual group after the first four weeks, but no difference between antidepressants and listening visits at the later follow-up. In addition, one study comparing sertraline with nortriptyline (a tricyclic antidepressant) found no difference in effectiveness (109 participants).Side effects were experienced by a substantial proportion of women, but there was no evidence of a meaningful difference in the number of adverse effects between treatment arms in any study. There were very limited data on adverse effects experienced by breastfed infants, with no long-term follow-up. All but one of the studies were assessed as being at high or uncertain risk of attrition bias and selective outcome reporting. In particular, one of the placebo-controlled studies had over 50% drop-out.
AUTHORS' CONCLUSIONS: The evidence base for this review was very limited, with a small number of studies and little information on a number of important outcomes, particularly regarding potential effects on the child. Risk of bias, for example from high attrition rates, as well as low representativeness of participants (e.g. exclusion of women with severe or chronic depression in several trials) also limit the conclusions that can be drawn.Pooled estimates for response and remission found that SSRIs were significantly more effective than placebo for women with postnatal depression. However the quality of evidence contributing to this comparison was assessed as very low owing to the small sample size for this comparison (146 participants from three studies), the risk of bias in included studes and the inclusion of one study where all participants in both study arms additionally received psychological therapy. There was insufficient evidence to conclude whether, and for whom, antidepressant or psychological/psychosocial treatments are more effective, or whether some antidepressants are more effective or better tolerated than others. There is also inadequate evidence on whether the benefits of antidepressants persist beyond eight weeks or whether they have short- or long-term adverse effects on breastfeeding infants.Professionals treating women with severe depression in the postnatal period will need to draw on other evidence, including trials among general adult populations and observational studies of antidepressant safety when breastfeeding (although the potential for confounding in non-randomised studies must be considered). More RCTs are needed with larger sample sizes and longer follow-up, including assessment of the impact on the child and safety of breastfeeding. Further larger-scale trials comparing antidepressants with alternative treatment modalities are also required.
产后抑郁症是一种常见疾病,会对产妇的短期和长期健康、新生儿以及整个家庭产生不良影响。治疗通常主要依靠社会支持和心理干预。目前尚不清楚抗抑郁药是否是治疗该疾病的有效且安全的选择。本综述旨在评估不同抗抑郁药的有效性,并将其有效性与其他治疗形式、安慰剂或常规治疗进行比较。这是对2001年首次发表的一篇综述的更新。
评估抗抑郁药与其他任何治疗方法(心理、社会心理或药物治疗)、安慰剂或常规治疗相比,治疗产后抑郁症的有效性。
我们检索了Cochrane抑郁、焦虑和神经症小组专业注册库(CCDANCTR)至2014年7月11日的数据。该注册库包含来自以下文献数据库的相关随机对照试验(RCT)报告:Cochrane图书馆(所有年份)、MEDLINE(1950年至今)、EMBASE(1974年至今)和PsycINFO(1967年至今)。我们还检索了国际试验注册库,并联系了制药公司和该领域的专家。
我们纳入了产后六个月内发病的抑郁症女性的RCT,这些试验比较了抗抑郁药治疗(单独或与其他治疗联合)与其他任何治疗、安慰剂或常规治疗。
两位综述作者独立从试验报告中提取数据。我们尽可能向研究者索要缺失信息。我们寻求数据以进行意向性分析。在确定有足够可比研究的情况下,进行随机效应荟萃分析以汇总数据。
本综述纳入了六项试验,共596名参与者。所有研究均采用随机对照平行组设计,其中两项在英国进行,三项在美国进行,一项在以色列进行。对比较抗抑郁药与安慰剂的研究的数据进行荟萃分析,以汇总关于反应和缓解的数据。由于确定的试验数量较少,无法对其他比较进行荟萃分析。四项研究比较了选择性5-羟色胺再摄取抑制剂(SSRI)与安慰剂(两项使用舍曲林,一项使用帕罗西汀,一项使用氟西汀;共233名参与者)。在其中两项研究中,试验组和安慰剂组均接受了心理治疗。基于其中三项研究(146名参与者)的数据汇总风险比显示,随机分配到SSRI组的女性比随机分配到安慰剂组的女性有更高的反应率和缓解率(反应:RR 1.43,95% CI 1.01至2.03;缓解:RR 1.79,95% CI 1.08至2.98);第四项研究未报告反应或缓解的数据。一项研究(254名参与者)比较了抗抑郁药治疗与常规治疗(前四周),随后进行随访。该研究发现,在前四周后,抗抑郁药组的改善率显著高于常规治疗组,但在后期随访中,抗抑郁药与随访之间没有差异。此外,一项比较舍曲林与去甲替林(一种三环类抗抑郁药)的研究发现,有效性没有差异(109名参与者)。相当一部分女性经历了副作用,但在任何研究中,各治疗组之间不良反应的数量均无显著差异的证据。关于母乳喂养婴儿经历的不良反应的数据非常有限,且没有长期随访。除一项研究外,所有研究均被评估为存在高或不确定的失访偏倚和选择性结果报告风险。特别是,一项安慰剂对照研究的失访率超过50%。
本综述的证据基础非常有限,研究数量少,且关于许多重要结果的信息很少,尤其是对儿童的潜在影响。偏倚风险,例如高失访率,以及参与者的低代表性(例如在多项试验中排除了患有严重或慢性抑郁症的女性)也限制了可以得出结论。对反应和缓解的汇总估计发现,对于产后抑郁症女性,SSRI比安慰剂显著更有效。然而,由于该比较的样本量小(来自三项研究的146名参与者)、纳入研究中的偏倚风险以及一项研究中两个研究组的所有参与者均额外接受了心理治疗,因此该比较的证据质量被评估为非常低。没有足够的证据来确定抗抑郁药或心理/社会心理治疗是否更有效,以及对谁更有效,或者某些抗抑郁药是否比其他抗抑郁药更有效或耐受性更好。关于抗抑郁药的益处是否持续超过八周,或者它们是否对母乳喂养婴儿有短期或长期不良影响,也没有足够的证据。治疗产后严重抑郁症女性的专业人员将需要借鉴其他证据,包括一般成年人群的试验以及母乳喂养时抗抑郁药安全性的观察性研究(尽管必须考虑非随机研究中的混杂可能性)。需要更多样本量更大、随访时间更长的RCT,包括评估对儿童的影响和母乳喂养的安全性。还需要进一步进行更大规模的试验,比较抗抑郁药与替代治疗方式。