Sindrup Søren H, Otto Marit, Finnerup Nanna B, Jensen Troels S
Department of Neurology, Odense University Hospital, DK-5000 Odense, Denmark.
Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409. doi: 10.1111/j.1742-7843.2005.pto_96696601.x.
Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4-5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class--may among the antidepressants--favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain.
神经性疼痛是由外周或中枢神经系统的损伤或功能障碍引起的。三环类抗抑郁药和抗惊厥药长期以来一直是这类疼痛治疗的主要药物。三环类抗抑郁药可能通过其独特的抑制生物胺5-羟色胺和去甲肾上腺素突触前再摄取的能力来缓解神经性疼痛，但其他机制如N-甲基-D-天冬氨酸受体和离子通道阻滞可能在其镇痛作用中也发挥作用。三环类抗抑郁药在人类神经性疼痛中的作用已在众多随机对照试验中得到证实，一些试验表明，5-羟色胺去甲肾上腺素和选择性5-羟色胺再摄取抑制剂类抗抑郁药也能缓解神经性疼痛，尽管疗效较低。三环类抗抑郁药能使每2-3名外周神经性疼痛患者中的1人得到缓解，5-羟色胺去甲肾上腺素再摄取抑制剂能使每4-5名患者中的1人得到缓解，选择性5-羟色胺再摄取抑制剂能使每7名患者中的1人得到缓解。因此，基于治疗所需人数等疗效指标，三环类抗抑郁药往往比抗惊厥药加巴喷丁以及曲马多和羟考酮等治疗选择效果更好，而5-羟色胺去甲肾上腺素再摄取抑制剂文拉法辛似乎与这些药物效果相当，选择性5-羟色胺再摄取抑制剂显然疗效较低。抗抑郁药与其他镇痛药之间缺乏直接对比研究。三环类抗抑郁药的使用禁忌以及这类药物总体耐受性较低——在抗抑郁药中可能如此——使得5-羟色胺去甲肾上腺素再摄取抑制剂更受青睐。最近一项关于安非他酮（一种去甲肾上腺素和多巴胺摄取抑制剂）的研究表明，该药在外周神经性疼痛中具有出人意料的高疗效。总之，抗抑郁药是神经性疼痛治疗的有用工具，仍应被视为神经性疼痛的一线治疗药物。然而，由于抗抑郁药与其他镇痛药之间缺乏直接对比研究，无法提供基于实际证据的神经性疼痛治疗方案。
