Banzi Rita, Cusi Cristina, Randazzo Concetta, Sterzi Roberto, Tedesco Dario, Moja Lorenzo
Laboratory of Regulatory Policies, IRCCS - Mario Negri Institute for Pharmacological Research, via G La Masa 19, Milan, Italy, 20156.
Cochrane Database Syst Rev. 2015 Apr 1;4(4):CD002919. doi: 10.1002/14651858.CD002919.pub3.
This is an updated version of the original Cochrane review published in 2005 on selective serotonin reuptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards migraine prevention. Another updated review is under development to cover tension-type headache.Migraine is a common disorder. The chronic forms are associated with disability and have a high economic impact. In view of discoveries about the role of serotonin and other neurotransmitters in pain mechanisms, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of migraine.
To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic migraine in adults.
For the original review, we searched MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), and Headache Quarterly (1990 to 2003). For this update, we applied a revised search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10), MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials.
We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older of either sex with migraine.
Two authors independently extracted data (migraine frequency, index, intensity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the risk of bias of trials. The primary outcome of this updated review is migraine frequency.
The original review included eight studies on migraine. Overall, we now include 11 studies on five SSRIs and one SNRI with a total of 585 participants. Six studies were placebo-controlled, four compared a SSRI or SNRI to amitriptyline, and one was a head-to-head comparison (escitalopram versus venlafaxine). Most studies had methodological or reporting shortcomings (or both): all studies were at unclear risk of selection and reporting bias. Follow-up rarely extended beyond three months. The lack of adequate power of most of the studies is also a major concern.Few studies explored the effect of SSRIs or SNRIs on migraine frequency, the primary endpoint. Two studies with unclear reporting compared SSRIs and SNRIs to placebo, suggesting a lack of evidence for a difference. Two studies compared SSRIs or SNRIs versus amitriptyline and found no evidence for a difference in terms of migraine frequency (standardised mean difference (SMD) 0.04, 95% confidence interval (CI) -0.72 to 0.80; I(2) = 72%), or other secondary outcomes such as migraine intensity and duration.SSRIs or SNRIs were generally more tolerable than tricyclics. However, the two groups did not differ in terms of the number of participants who withdrew due to adverse advents or for other reasons (one study, odds ratio (OR) 0.39, 95% CI 0.10 to 1.50 and OR 0.42, 95% CI 0.13 to 1.34).We did not find studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. antiepileptics and anti-hypertensives).
AUTHORS' CONCLUSIONS: Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine as preventive drugs for migraine. There is no evidence to consider SSRIs or venlafaxine as more effective than placebo or amitriptyline in reducing migraine frequency, intensity, and duration over two to three months of treatment. No reliable information is available at longer-term follow-up. Our conclusion is that the use of SSRIs and SNRIs for migraine prophylaxis is not supported by evidence.
这是2005年发表的关于选择性5-羟色胺再摄取抑制剂（SSRIs）预防偏头痛和紧张型头痛的Cochrane系统评价的更新版本。原系统评价已分为两部分，本系统评价现仅涉及偏头痛预防。另一项关于紧张型头痛预防的更新系统评价正在撰写中。偏头痛是一种常见疾病。慢性偏头痛与功能障碍相关，且具有较高的经济影响。鉴于5-羟色胺及其他神经递质在疼痛机制中的作用已被发现，人们对选择性5-羟色胺再摄取抑制剂（SSRIs）和5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）预防偏头痛进行了评估。
确定与安慰剂及其他有效干预措施相比，SSRIs和SNRIs预防成人发作性和慢性偏头痛的疗效和耐受性。
对于原系统评价，我们检索了MEDLINE（1966年至2004年1月）、EMBASE（1994年至2003年5月）、Cochrane对照试验中心注册库（CENTRAL 2003年第4期）和《头痛季刊》（1990年至2003年）。对于本次更新，我们采用了修订后的检索策略以反映更广泛的干预类型（SSRIs和SNRIs）。我们检索了CENTRAL（2014年第10期）、MEDLINE（1946年至2014年11月）、EMBASE（1980年至2014年11月）和PsycINFO（1987年至2014年11月）。我们还检查了检索到的文章的参考文献列表，并在试验注册库中检索正在进行的试验。
我们纳入了比较SSRIs或SNRIs与任何类型对照干预措施的随机对照试验，参与者为18岁及以上患有偏头痛的成年男女。
两位作者独立提取数据（偏头痛发作频率、指数、强度和持续时间；对症/止痛药物的使用；误工天数；生活质量；情绪改善；成本效益；以及不良事件）并评估试验的偏倚风险。本次更新系统评价的主要结局是偏头痛发作频率。
原系统评价纳入了8项关于偏头痛的研究。总体而言，我们现在纳入了11项关于5种SSRIs和1种SNRIs的研究，共有585名参与者。6项研究为安慰剂对照，4项研究将一种SSRI或SNRI与阿米替林进行了比较，1项研究为直接比较（艾司西酞普兰与文拉法辛）。大多数研究存在方法学或报告方面的缺陷（或两者皆有）：所有研究在选择和报告偏倚方面的风险均不明确。随访很少超过3个月。大多数研究缺乏足够的检验效能也是一个主要问题。很少有研究探讨SSRIs或SNRIs对主要终点偏头痛发作频率的影响。两项报告不明确的研究将SSRIs和SNRIs与安慰剂进行了比较，表明缺乏两者存在差异的证据。两项研究将SSRIs或SNRIs与阿米替林进行了比较，未发现偏头痛发作频率方面存在差异的证据（标准化均数差（SMD）0.04，95%置信区间（CI）-0.72至0.80；I² = 72%），或其他次要结局如偏头痛强度和持续时间方面存在差异的证据。SSRIs或SNRIs通常比三环类药物耐受性更好。然而，两组因不良事件或其他原因退出的参与者数量没有差异（一项研究，比值比（OR）0.39，95%CI 0.10至1.50和OR 0.42，95%CI 0.13至1.34）。我们未找到将SSRIs或SNRIs与除抗抑郁药之外的其他药物治疗（如抗癫痫药和抗高血压药）进行比较的研究。
自本系统评价的上一版本以来，新纳入的研究未增加高质量证据以支持使用SSRIs或文拉法辛作为偏头痛的预防性药物。没有证据表明在治疗两至三个月期间，SSRIs或文拉法辛在降低偏头痛发作频率、强度和持续时间方面比安慰剂或阿米替林更有效。长期随访时没有可靠信息。我们的结论是，证据不支持使用SSRIs和SNRIs预防偏头痛。
