Ayub Shahana, Bachu Anil Krishna, Jain Lakshit, Parnia Shanli, Bhivandkar Siddhi, Ahmed Rizwan, Kaur Jasleen, Karlapati Surya, Prasad Sakshi, Kochhar Hansini, Ayisire Oghenetega Esther, Mitra Saloni, Ghosh Bikona, Srinivas Sushma, Ashraf Sahar, Papudesi Bhavani Nagendra, Malo Palash Kumar, Sheikh Shoib, Hsu Michael, De Berardis Domenico, Ahmed Saeed
Department of Psychiatry, The Institute of Living, Hartford, CT, United States.
Department of Psychiatry, Atrium Behavior Health, Charlotte, NC, United States.
Front Pain Res (Lausanne). 2024 Oct 10;5:1398442. doi: 10.3389/fpain.2024.1398442. eCollection 2024.
The escalating number of deaths related to opioid usage has intensified the pursuit of non-opioid alternatives for managing chronic pain. It's often observed that psychiatric comorbidities coexist in patients suffering from chronic pain. There are a variety of psychotropic medications that have demonstrated effectiveness in treating both psychiatric symptoms and pain. This systematic review and meta-analysis aim to assess the effectiveness of various psychiatric drugs in managing specific types of chronic pain, including fibromyalgia, neuropathic pain, and chronic low back pain.
A comprehensive search of five major databases was conducted through February 2023 to identify randomized controlled trials (RCTs) that met our inclusion criteria, focusing on outpatients Over 18 years of age with chronic pain. The study assessed the effectiveness of duloxetine, mirogabalin, pregabalin, gabapentin, and tricyclic antidepressants (TCAs), including serotonin-norepinephrine reuptake inhibitors (SNRIs), across various chronic pain conditions such as fibromyalgia, neuropathic pain, and chronic low back pain. The primary outcome measures included pain reduction, improvement in function, and quality of life. Of the 29 RCTs in the systematic review, 20 studies qualified for the meta-analysis. The analysis was stratified by pain type and treatment duration (short-term ≤14 weeks vs. long-term >14 weeks), using Hedge's g standardized mean differences and a random-effects model, along with sensitivity and subgroup analyses.
The overall short-term intervention effect across all studies was significant (SMD -1.45, 95% CI -2.15 to -0.75, < 0.001), with considerable heterogeneity (I = 99%). For fibromyalgia, both duloxetine and mirogabalin demonstrated substantial efficacy with SMDs of -2.42 (95% CI -3.67 to -1.18, < 0.0001) and -2.10 (95% CI -3.28 to -0.92, = 0.0005), respectively. Conversely, treatments for neuropathic pain and chronic low back pain, including those with amitriptyline and desipramine, did not show significant benefits. The effectiveness of gabapentin could not be conclusively determined due to limited representation in the data. Additionally, no consistent long-term benefits were observed for any of the medications.
While the results of this study underscore the importance of exploring non-opioid alternatives for chronic pain management, particularly in light of the opioid crisis, it is crucial to interpret the findings carefully. Our analysis suggests that certain psychiatric medications, such Duloxetine and mirogabalin demonstrated significant short-term efficacy in fibromyalgia patients. However, their effectiveness in treating neuropathic pain and chronic low back pain was not statistically significant. Additionally, the effectiveness of gabapentin and other medications, such as pregabalin for neuropathic pain, could not be conclusively determined due to limited data and high study heterogeneity. No consistent long-term benefits were observed for any of the drugs studied, raising questions about their sustained efficacy in chronic pain management. These findings highlight the need for further research to understand better the role of psychiatric medications in managing specific chronic pain conditions without prematurely concluding that they are ineffective or unsuitable for these purposes.
与阿片类药物使用相关的死亡人数不断上升，这加剧了人们对用于管理慢性疼痛的非阿片类替代药物的追求。人们经常观察到，慢性疼痛患者中常常并存精神疾病合并症。有多种精神药物已证明在治疗精神症状和疼痛方面均有效。本系统评价和荟萃分析旨在评估各种精神药物在管理特定类型慢性疼痛（包括纤维肌痛、神经性疼痛和慢性下腰痛）方面的有效性。
截至2023年2月，对五个主要数据库进行了全面检索，以识别符合纳入标准的随机对照试验（RCT），重点关注18岁以上患有慢性疼痛的门诊患者。该研究评估了度洛西汀、米罗加巴林、普瑞巴林、加巴喷丁和三环类抗抑郁药（TCA）（包括5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI））在各种慢性疼痛状况（如纤维肌痛、神经性疼痛和慢性下腰痛）中的有效性。主要结局指标包括疼痛减轻、功能改善和生活质量。在系统评价的29项RCT中，有20项研究符合荟萃分析的条件。分析按疼痛类型和治疗持续时间（短期≤14周与长期>14周）进行分层，使用赫奇斯g标准化均数差值和随机效应模型，以及敏感性和亚组分析。
所有研究的总体短期干预效果显著（标准化均数差值-1.45，95%置信区间-2.15至-0.75，P<0.001），存在相当大的异质性（I²=99%）。对于纤维肌痛，度洛西汀和米罗加巴林均显示出显著疗效，标准化均数差值分别为-2.42（95%置信区间-3.67至-1.18，P<0.0001）和-2.10（95%置信区间-3.28至-0.92，P=0.0005）。相反，包括阿米替林和地昔帕明在内的神经性疼痛和慢性下腰痛的治疗未显示出显著益处。由于数据中的代表性有限，加巴喷丁的有效性无法最终确定。此外，未观察到任何一种药物有一致的长期益处。
虽然本研究结果强调了探索用于慢性疼痛管理的非阿片类替代药物的重要性，特别是鉴于阿片类药物危机，但仔细解读研究结果至关重要。我们的分析表明，某些精神药物，如度洛西汀和米罗加巴林，在纤维肌痛患者中显示出显著的短期疗效。然而，它们在治疗神经性疼痛和慢性下腰痛方面的有效性在统计学上并不显著。此外，由于数据有限和研究异质性高，加巴喷丁和其他药物（如用于神经性疼痛的普瑞巴林）的有效性无法最终确定。未观察到所研究的任何一种药物有一致的长期益处，这引发了关于它们在慢性疼痛管理中持续疗效的疑问。这些发现凸显了进一步研究的必要性，以便更好地理解精神药物在管理特定慢性疼痛状况中的作用，而不是过早地得出它们无效或不适用于这些目的的结论。
