Objectives

A refractory chronic migraine (RCM) accompanied by medication-overuse headache (MOH) is an extremely disabling disease. Evidence suggests that in selected patients, chronic opioids may be a valuable therapeutic option for RCM. The aim of the present study was to evaluate the effectiveness and safety of prophylaxis with low-dose methadone (LDM) in patients affected by RCM with continuous headache and MOH.

Methods

A prospective cohort study was performed between May 2012 and November 2015 at the Headache Center and Toxicology Unit of the Careggi University Hospital. Eligible patients were treated with prophylactic LDM and followed up for 12 months. Headache exacerbations, pain intensity, use of rescue medications, and occurrence of adverse drug reactions (ADRs) were recorded.

Results

Thirty patients (24 females, median age 48 years) were enrolled. Nineteen (63%) patients dropped out, mainly because of early ADRs (n = 10), including nausea, vomiting, and constipation. At last available follow-up, LDM was associated with a significant decrease in the number of headache attacks/month (from a median of 45 (interquartile range 30–150) to 16 (5–30), p < 0.001), in pain intensity (from 8.5 (8–9) to 5 (3–6), p < 0.001), and in the number of rescue medications consumed per month (from 95 (34–240) to 15 (3–28), p < 0.001). No misuse or diversion cases were observed.

Conclusion

LDM could represent a valuable and effective option in selected patients affected by RCM with continuous headache and MOH, although the frequency of early ADRs poses major safety concerns. Randomized controlled trials are needed to confirm the efficacy and safety of LDM prophylaxis.

中文翻译：

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低剂量美沙酮治疗伴有药物过度使用性头痛的难治性慢性偏头痛：一项前瞻性队列研究。

目标

伴有药物过度使用性头痛 (MOH) 的难治性慢性偏头痛 (RCM) 是一种极其致残的疾病。证据表明，在选定的患者中，慢性阿片类药物可能是 RCM 的一种有价值的治疗选择。本研究的目的是评估低剂量美沙酮 (LDM) 对患有持续性头痛和 MOH 的 RCM 患者进行预防的有效性和安全性。

方法

2012 年 5 月至 2015 年 11 月期间，在 Careggi 大学医院的头痛中心和毒理学部门进行了一项前瞻性队列研究。符合条件的患者接受预防性 LDM 治疗并随访 12 个月。记录头痛恶化、疼痛强度、急救药物的使用和药物不良反应 (ADR) 的发生情况。

结果

招募了 30 名患者（24 名女性，中位年龄 48 岁）。19 名 (63%) 患者退出，主要是因为早期 ADR ( n  = 10)，包括恶心、呕吐和便秘。在最后一次可用的随访中，LDM 与疼痛发作次数/月的显着减少相关（从中位数 45（四分位距 30-150）到 16（5-30），p  < 0.001）强度（从 8.5 (8-9) 到 5 (3-6)，p  < 0.001），每月消耗的急救药物数量（从 95 (34-240) 到 15 (3-28)，p  < 0.001)。没有观察到滥用或转移案件。

结论

LDM 可能代表受 RCM 影响并伴有持续性头痛和 MOH 的选定患者的一种有价值和有效的选择，尽管早期 ADR 的频率构成了主要的安全问题。需要随机对照试验来确认 LDM 预防的有效性和安全性。