Antidepressants for pain management in adults with chronic pain: a network meta-analysis.
Antidepressants for pain management in adults with chronic pain: a network meta-analysis.
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DOI：
10.1002/14651858.cd014682.pub2
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发表时间：
2023-05-10
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影响因子：
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通讯作者：
Pincus, Tamar
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作者：
Birkinshaw, Hollie;Friedrich, Claire M;Pincus, Tamar
背景：慢性疼痛在成年人中很常见，通常对身体能力、健康和生活质量产生不利影响。以前的综述表明，某些抗抑郁药可能有效地减轻疼痛，并在改善患者对某些慢性疼痛状况的总体印象方面有一定的益处。然而，还没有一个网络荟萃分析（NMA）检查所有抗抑郁药对所有慢性疼痛条件。补充资料：评估抗抑郁药对慢性疼痛成人的比较疗效和安全性（头痛除外）。我们检索了CENTRAL、MEDLINE、Embase、CINAHL、LILACS、AMED和PsycINFO数据库，以及临床试验登记处，选择标准：我们纳入了与任何对照药物相比检查抗抑郁药治疗慢性疼痛的随机对照试验（RCT）。如果对照药物是安慰剂、另一种药物、另一种抗抑郁药或不同剂量的同一种抗抑郁药，那么我们要求该研究是双盲的。我们纳入了使用活性对照药物的RCT，这些对照药物无法进行双盲（例如心理治疗），但将其评定为高偏倚风险。我们排除了随机对照试验的后续行动是不到两个星期，那些少于10名参与者在每个arm.Data收集和分析：两个审查作者分别筛选，数据提取，并判断风险的偏见。我们使用贝叶斯NMA和成对荟萃分析对每个结果进行数据综合，并使用累积排名曲线下的表面（SUCRA）根据抗抑郁药的有效性对它们进行排名。我们主要使用荟萃分析置信度（CINeMA）和网络荟萃分析中缺失证据导致的偏倚风险（ROB-MEN）来评估证据的确定性。由于网络的复杂性，无法使用CineMA和ROB-MEN，我们使用GRADE来评估证据的确定性。我们的主要结局是疼痛缓解、疼痛强度、情绪和不良事件的显著性（50%）。我们的次要结果是中度疼痛缓解（30%），身体功能，睡眠，生活质量，患者总体印象的变化（PGIC），严重不良事件，和withdrawing.Main结果：本次审查和NMA包括176项研究，共28,664名参与者。大多数研究为安慰剂对照（83）和平行组（141）。检查的最常见的疼痛状况是纤维肌痛（59项研究）;神经性疼痛（49项研究）和肌肉骨骼疼痛（40项研究）。随机对照试验的平均时间为10周。7项研究未提供可用数据，因此从NMA中删除。大多数研究仅测量短期结果，排除了情绪低落和其他心理健康状况的人。在疗效结局中，度洛西汀始终是排名最高的抗抑郁药，具有中度至高度确定性证据。在度洛沙汀研究中，标准剂量与高剂量对大多数结局同样有效。米那普仑通常被列为下一个最有效的抗抑郁药，尽管证据的确定性低于度洛西汀。没有足够的证据得出任何其他抗抑郁药治疗慢性疼痛的有效性和安全性的有力结论。主要有效性结局度洛沙汀标准剂量（60 mg）显示了小至中度的疼痛缓解效果（比值比（OR）1.91，95%置信区间（CI）1.69 - 2.17; 16项研究，4490例受试者;中度确定性证据）和持续疼痛强度（标准化平均差异（SMD）-0.31，95%CI-0.39至-0.24; 18项研究，4959名参与者;中度确定性证据）。对于疼痛强度，米那普仑标准剂量（100 mg）也显示出较小的影响（SMD-0.22，95% CI-0.39至0.06; 4项研究，1866例受试者;中等确定性证据）。米氮平（30 mg）对情绪有中度影响（SMD-0.5，95% CI-0.78至-0.22; 1项研究，406例受试者;低确定性证据），而度洛西汀显示出较小的影响（SMD-0.16，95% CI-0.22至-0.1; 26项研究，7952名受试者;中等确定性证据）;然而，值得注意的是，大多数研究排除了有精神健康状况的参与者，因此平均焦虑和抑郁评分在基线时已经趋于"正常"或"亚临床"范围。次要疗效结果在所有次要疗效结果（中度疼痛缓解、身体功能、睡眠、生活质量和PGIC）中，度洛西汀和米那普仑是具有中度确定性证据的排名最高的抗抑郁药，尽管效果很小。对于度洛昔单抗和米那普仑，标准剂量与高剂量一样有效。安全性所有抗抑郁药的所有安全性结局（不良事件、严重不良事件和停药）的确定性证据都非常低。我们无法从NMA中得出任何可靠的结论。专家结论：我们的综述和NMA显示，尽管研究了25种不同的抗抑郁药，但我们唯一确定用于治疗慢性疼痛的抗抑郁药是度洛西汀。在标准剂量下，度洛沙汀在所有结局中均中度有效。米那普仑也有令人鼓舞的证据，尽管需要进一步的高质量研究才能对这些结论充满信心。所有其他抗抑郁药的证据都很低。由于随机对照试验排除了情绪低落的人，我们无法确定抗抑郁药对慢性疼痛和抑郁症患者的影响。目前没有可靠的证据证明任何抗抑郁药的长期疗效，也没有可靠的证据证明抗抑郁药在任何时间点对慢性疼痛的安全性。
BACKGROUND: Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.OBJECTIVES: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.SELECTION CRITERIA: We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.MAIN RESULTS: This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.AUTHORS' CONCLUSIONS: Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.