Hong James S W, Atkinson Lauren Z, Al-Juffali Noura, Awad Amine, Geddes John R, Tunbridge Elizabeth M, Harrison Paul J, Cipriani Andrea
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.
Oxford Centre for Human Brain Activity, University of Oxford, Oxford, UK.
Mol Psychiatry. 2022 Mar;27(3):1339-1349. doi: 10.1038/s41380-021-01386-6. Epub 2021 Nov 24.
The gabapentinoids, gabapentin, and pregabalin, target the αδ subunits of voltage-gated calcium channels. Initially licensed for pain and seizures, they have become widely prescribed drugs. Many of these uses are off-label for psychiatric indications, and there is increasing concern about their safety, so it is particularly important to have good evidence to justify this usage. We conducted a systematic review and meta-analysis of the evidence for three of their common psychiatric uses: bipolar disorder, anxiety, and insomnia. Fifty-five double-blind randomised controlled trials (RCTs) and 15 open-label studies were identified. For bipolar disorder, four double-blind RCTs investigating gabapentin, and no double-blind RCTs investigating pregabalin, were identified. A quantitative synthesis could not be performed due to heterogeneity in the study population, design and outcome measures. Across the anxiety spectrum, a consistent but not universal effect in favour of gabapentinoids compared to placebo was seen (standardised mean difference [SMD] ranging between -2.25 and -0.25). Notably, pregabalin (SMD -0.55, 95% CI -0.92 to -0.18) and gabapentin (SMD -0.92, 95% CI -1.32 to -0.52) were more effective than placebo in reducing preoperative anxiety. In insomnia, results were inconclusive. We conclude that there is moderate evidence of the efficacy of gabapentinoids in anxiety states, but minimal evidence in bipolar disorder and insomnia and they should be used for these disorders only with strong justification. This recommendation applies despite the attractive pharmacological and genetic rationale for targeting voltage-gated calcium channels.
加巴喷丁类药物，即加巴喷丁和普瑞巴林，作用于电压门控性钙通道的αδ亚基。它们最初获批用于治疗疼痛和癫痫，如今已成为广泛使用的处方药。这些药物的许多用途都属于精神科适应症的超说明书用药，人们对其安全性的担忧也与日俱增，因此，有充分的证据来证明这种用药的合理性尤为重要。我们对它们常见的三种精神科用途（双相情感障碍、焦虑症和失眠症）的证据进行了系统评价和荟萃分析。共识别出55项双盲随机对照试验（RCT）和15项开放标签研究。对于双相情感障碍，识别出4项研究加巴喷丁的双盲RCT，但未识别出研究普瑞巴林的双盲RCT。由于研究人群、设计和结局指标存在异质性，无法进行定量综合分析。在整个焦虑症范围内，与安慰剂相比，加巴喷丁类药物显示出一致但并非普遍的效果（标准化均数差[SMD]在-2.25至-0.25之间）。值得注意的是，普瑞巴林（SMD -0.55，95%CI -0.92至-0.18）和加巴喷丁（SMD -0.92，95%CI -1.32至-0.52）在减轻术前焦虑方面比安慰剂更有效。在失眠症方面，结果尚无定论。我们得出结论，有中等证据表明加巴喷丁类药物在焦虑状态下有效，但在双相情感障碍和失眠症方面证据极少，仅在有充分理由时才可用于这些疾病。尽管针对电压门控性钙通道有诱人的药理学和遗传学理论依据，但本建议仍然适用。
