Göbel H, Stadler T
Service de Neurologie, Hôpital Universitaire, Kiel, Allemagne.
Drugs. 1997;53 Suppl 2:34-9. doi: 10.2165/00003495-199700532-00008.
To date, no universally applicable recommendations are available for the treatment of patients with postherpetic neuralgia. A mixture of clinical anecdotes, experimental findings and observations from clinical trials form the basis of the medical arsenal for this condition. Tricyclic antidepressants are commonly used, and clinical experience and several investigations have documented their effectiveness. Today, single entity antidepressants, which can be combined with neuroleptics to increase analgesia, are generally recommended for the treatment of postherpetic neuralgia. Some authors also recommend the additional administration of an opioid if analgesia is inadequate. Just over a decade ago, opioids were considered ineffective for the treatment of neuropathic pain; however, more recent investigations relating to the use of opioids, primarily in the treatment of nontumour-related chronic pain, have led to a revision of their use in neuropathic pain. Nevertheless, the use of opioid therapy for neurogenic pain remains controversial. Tramadol is a synthetic, centrally acting analgesic with both opioid and nonopioid analgesic activity. The nonopioid component is related to the inhibition of noradrenaline (norepinephrine) reuptake and stimulation of serotonin (5-hydroxytryptamine; 5-HT) release at the spinal level. In this regard, there are parallels with antidepressants, which are believed to potentiate the effect of biogenic amines in endogenous pain-relieving systems. There is evidence that, in tramadol, both mechanisms act synergistically with respect to analgesia. The aim of this pilot study was to investigate, for the first time, the analgesic efficacy and tolerability of tramadol, compared with the antidepressant clomipramine, in the treatment of postherpetic neuralgia. If necessary, clomipramine was used in combination with the neuroleptic levomepromazine. The study allowed individualised dosages at predetermined intervals up to a maximum daily dose of tramadol 600mg and clomipramine 100mg, or clomipramine 100mg with or without levomepromazine 100mg. 21 (60%) of 35 randomised patients (> or = 65 years) received the study medication over the 6-week period [tramadol n = 10; clomipramine with or without levomepromazine) n = 11]. After 3 weeks' treatment the dosage in both groups remained almost constant for the rest of the 6-week treatment phase (mean daily dose: tramadol 250 to 290mg; clomipramine 59.1 to 63.6mg). Only 3 patients required the combination of clomipramine and levomepromazine. At the outset, both groups recorded an average pain level of 'moderate' to 'very severe'. In correlation with increasing the study medication, this had decreased to 'slight' by the end of the treatment, when 9 of 10 patients in the tramadol group and of 6 of 11 patients in the clomipramine group retrospectively rated their analgesia as excellent, good or satisfactory. The psychological/physical condition of the patients did not change significantly during tramadol treatment. Sensitivity and depression parameters decreased in the clomipramine group. The incidence of adverse events for all patients was similar in both groups (tramadol 76.5%; clomipramine with or without levomepromazine 83.3%). In conclusion, tramadol would appear to be an interesting therapeutic alternative for pain relief in postherpetic neuralgia, particularly in patients who are not depressed. In clinical practice, tramadol and clomipramine can best be used differentially. For example, tramadol could be the drug of first choice in patients with obvious cardiovascular disease (not an uncommon problem in the > or = 65 year age group) in whom antidepressants are contraindicated, and similarly in patients in whom an antidepressant effect is not required. (ABSTRACT TRUNCATED)
迄今为止,对于带状疱疹后神经痛患者的治疗,尚无普遍适用的建议。临床轶事、实验结果以及临床试验观察结果的综合构成了针对这种病症的医疗手段基础。三环类抗抑郁药常用,临床经验和多项研究已证明其有效性。如今,通常推荐使用可与抗精神病药物联合以增强镇痛效果的单一实体抗抑郁药来治疗带状疱疹后神经痛。一些作者还建议在镇痛效果不足时额外使用阿片类药物。就在十多年前,阿片类药物还被认为对治疗神经性疼痛无效;然而,最近有关阿片类药物使用的研究,主要是在治疗非肿瘤相关慢性疼痛方面,已导致其在神经性疼痛治疗中的应用有所改变。尽管如此,阿片类药物疗法用于神经源性疼痛仍存在争议。曲马多是一种合成的中枢性镇痛药,具有阿片类和非阿片类镇痛活性。非阿片类成分与抑制去甲肾上腺素再摄取以及在脊髓水平刺激5-羟色胺(5-羟色胺;5-HT)释放有关。在这方面,它与抗抑郁药有相似之处,抗抑郁药被认为可增强内源性疼痛缓解系统中生物胺的作用。有证据表明,在曲马多中,这两种机制在镇痛方面协同起作用。这项初步研究的目的是首次研究曲马多与抗抑郁药氯米帕明相比,在治疗带状疱疹后神经痛中的镇痛效果和耐受性。如有必要,氯米帕明可与抗精神病药物左美丙嗪联合使用。该研究允许在预定间隔进行个体化给药,曲马多最大日剂量为600mg,氯米帕明为100mg,或氯米帕明100mg加或不加左美丙嗪100mg。35名随机分组的患者(≥65岁)中有21名(60%)在6周期间接受了研究药物治疗[曲马多组n = 10;氯米帕明加或不加左美丙嗪组n = 11]。治疗3周后,在6周治疗阶段的剩余时间里,两组的剂量几乎保持不变(平均日剂量:曲马多250至290mg;氯米帕明59.1至63.6mg)。只有3名患者需要氯米帕明和左美丙嗪联合使用。一开始,两组记录的平均疼痛程度为“中度”至“非常严重”。随着研究药物剂量增加,到治疗结束时疼痛程度已降至“轻微”,此时曲马多组10名患者中有9名、氯米帕明组11名患者中有6名回顾性地将其镇痛效果评为优秀、良好或满意。在曲马多治疗期间,患者的心理/身体状况没有明显变化。氯米帕明组的敏感性和抑郁参数有所下降。两组所有患者的不良事件发生率相似(曲马多组76.5%;氯米帕明加或不加左美丙嗪组83.3%)。总之,曲马多似乎是缓解带状疱疹后神经痛疼痛的一种有趣的治疗选择,特别是对于没有抑郁的患者。在临床实践中,曲马多和氯米帕明可以最好地进行区别使用。例如,曲马多可以是患有明显心血管疾病(在≥65岁年龄组中并非罕见问题)且抗抑郁药禁忌的患者的首选药物,同样也适用于不需要抗抑郁作用的患者。(摘要截选)