Molyneaux Emma, Telesia Laurence A, Henshaw Carol, Boath Elizabeth, Bradley Eleanor, Howard Louise M
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. 2018 Apr 18;4(4):CD004363. doi: 10.1002/14651858.CD004363.pub3.
Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear whether antidepressants are effective for the prevention of postnatal depression and little is known about possible adverse effects for the mother and infant, particularly during breastfeeding. This is an update of a Cochrane Review last published in 2005.
To assess the effectiveness of antidepressant medication for the prevention of postnatal depression, in comparison with any other treatment, placebo or standard care.
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR ‒ both Studies and References), CENTRAL (Wiley), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), on 13 February 2018. We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov on 13 February 2018 to identify any additional unpublished or ongoing studies.
Randomised controlled trials (RCTs) of initiation of antidepressants (alone or in combination with another treatment), compared with any other treatment, placebo or standard care for the prevention of postnatal depression among women who were either pregnant or had given birth in the previous six weeks and were not currently depressed at baseline.
We used standard methodological procedures expected by Cochrane. We requested missing information from investigators wherever possible and sought data to allow intention-to-treat analyses.
Two trials including a total of 81 participants fulfilled the inclusion criteria for this review. All participants in both studies had a history of postnatal depression and were not taking antidepressant medication at baseline. Both trials were conducted by the same research group. Risk of bias was low or unclear in most domains for both studies. We were unable to perform a meta-analysis due to the small number of studies.One study compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression. In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (RR 0.96, 95% CI 0.36 to 2.59, very low quality evidence) in the first 17 weeks postpartum. One woman taking nortriptyline developed mania; and one side effect, constipation, was more common among women taking nortriptyline than those taking placebo.The second study compared sertraline with placebo. In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (RR 0.14, 95% CI 0.02 to 1.07, very low quality evidence). One woman taking sertraline had a hypomanic episode. Two side effects (dizziness and drowsiness) were more common among women taking sertraline than women taking placebo.Conclusions are limited by the small number of studies, small sample sizes and incomplete outcome data due to study drop-out which may have led to bias in the results. We have assessed the certainty of the evidence as very low, based on the GRADE system. No data were available on secondary outcomes of interest including child development, the mother‒infant relationship, breastfeeding, maternal daily functioning, family relationships or maternal satisfaction.
AUTHORS' CONCLUSIONS: Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.
产后抑郁很常见,除了对母亲造成发病风险外,还会对婴儿及整个家庭产生不良影响。目前尚不清楚抗抑郁药是否对预防产后抑郁有效,且对于母亲和婴儿可能产生的不良反应知之甚少,尤其是在母乳喂养期间。这是对2005年发表的Cochrane系统评价的更新。
评估与其他任何治疗、安慰剂或标准护理相比,抗抑郁药物预防产后抑郁的有效性。
我们于2018年2月13日检索了Cochrane常见精神障碍对照试验注册库(CCMDCTR——包括研究和参考文献)、CENTRAL(Wiley)、MEDLINE(OVID)、Embase(OVID)、PsycINFO(OVID)。我们还于2018年2月13日检索了世界卫生组织(WHO)试验平台(ICTRP)和ClinicalTrials.gov,以识别任何其他未发表或正在进行的研究。
随机对照试验(RCT),比较开始使用抗抑郁药(单独使用或与其他治疗联合使用)与任何其他治疗、安慰剂或标准护理,以预防在过去六周内怀孕或分娩且基线时无抑郁的女性产后抑郁。
我们采用了Cochrane预期的标准方法程序。我们尽可能向研究者索要缺失信息,并寻求数据以进行意向性分析。
两项试验共纳入81名参与者,符合本评价的纳入标准。两项研究中的所有参与者均有产后抑郁病史,且基线时未服用抗抑郁药物。两项试验均由同一研究小组开展。两项研究在大多数领域的偏倚风险较低或不明确。由于研究数量较少,我们无法进行Meta分析。一项研究比较了去甲替林与安慰剂,未发现任何证据表明去甲替林对预防产后抑郁有效。在本研究中,服用去甲替林的女性中有23%(6/26)和服用安慰剂的女性中有24%(6/25)在产后17周内出现产后抑郁(RR 0.96,95%CI 0.36至2.59,极低质量证据)。一名服用去甲替林的女性出现躁狂;服用去甲替林的女性中便秘这一副作用比服用安慰剂的女性更常见。第二项研究比较了舍曲林与安慰剂。在本研究中,服用舍曲林的女性中有7%(1/14)在产后17周内出现产后抑郁,而服用安慰剂的女性中有50%(4/8)出现产后抑郁。尚不确定舍曲林是否能降低产后抑郁风险(RR 0.14,95%CI 0.02至1.07,极低质量证据)。一名服用舍曲林的女性出现轻躁狂发作。服用舍曲林的女性中头晕和嗜睡这两种副作用比服用安慰剂的女性更常见。由于研究数量少、样本量小以及因研究失访导致的结局数据不完整,可能导致结果出现偏倚,本评价的结论受到限制。基于GRADE系统,我们将证据的确定性评估为极低。关于包括儿童发育、母婴关系、母乳喂养、母亲日常功能、家庭关系或母亲满意度等感兴趣的次要结局,没有可用数据。
由于现有证据基础存在局限性,如纳入研究的统计效力较低,因此无法就抗抑郁药预防产后抑郁的有效性得出任何明确结论。令人惊讶的是,自本评价的上一版发表后的十多年里,没有完成任何新的符合条件的试验。需要开展更大规模的试验,包括比较抗抑郁药物与其他预防性治疗(如心理干预),并研究对胎儿或婴儿的不良反应。该领域未来的评价可能会受益于拓宽其关注点,以研究抗抑郁药预防围产期(即产前或产后)抑郁的有效性,这可能包括比较在预防孕期和产后抑郁复发时停用与继续使用抗抑郁药的研究。