度洛西汀与硫酸吗啡联合治疗癌痛的临床观察

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (10): 1138-1143.

度洛西汀与硫酸吗啡联合治疗癌痛的临床观察

戴志远¹, 郑芳¹, 李德强²

¹浙江省杭州市小营街道社区卫生服务中心,杭州 310003,浙江;
²浙江大学附属第一医院,杭州 310003,浙江

收稿日期:2012-09-03 修回日期:2013-09-07 出版日期:2013-10-26 发布日期:2013-09-30
作者简介:戴志远,女,主治医师,主要从事预防保健工作。E-mail: hzdzy888888@163.com;李德强,男,博士,主治医师,主要从事老年性疾病的基础与临床工作。Tel: 0571-86995953 E-mail: hzzjuldq@163.com
基金资助:
浙江省卫生厅科研基金(N20110317)

Clinical trial in the relief of cancer pain in a combined therapy by Duloxetine plus Morphine sulfate

DAI Zhi-yuan¹, ZHENG Fang¹, LI De-qiang²

¹Community Health Service Center, Hangzhou Xiaoying Street, Hangzhou 310003, Zhejiang;
²The First Affliated Hospital, Zhejiang University, Hangzhou 310003, Zhejiang,China

Received:2012-09-03 Revised:2013-09-07 Online:2013-10-26 Published:2013-09-30

摘要/Abstract

摘要： 目的:对比观察度洛西汀与硫酸吗啡缓释片与单用硫酸吗啡治疗癌痛的疗效与安全性,为肿瘤疼痛管理提供参考。方法:180例中重度癌痛患者被纳入这项随机、开放、为期12周的临床研究。研究对象均分入单药治疗组(硫酸吗啡缓释片,100~200 mg/d)和合并治疗组(同等剂量的硫酸吗啡缓释片+度洛西汀,前2周 30 mg/d,2周后 60 mg/d)。分别在基线及治疗后第4、8及12周进行随访与评估。用Short-Form McGill Pain Questionnaire (SF-MPQ)和the 10-point visual analog scale (VAS)行疼痛评估。焦虑抑郁症状采用汉密尔顿焦虑与抑郁量表评估。采用治疗时出现的不良事件量表与脱落率评估耐受性。结果:单药治疗组与合并治疗组脱落率相似(第4周 8.9% vs 10.0%,第8周 15.6% vs 17.8% 及第12周 23.3% vs 25.6%,均P>0.05)。虽然便秘、出汗和心悸的不良反应频数合并治疗组较高,但差异未达统计学意义。在第4、12周VAS评分减分值合并治疗组显著高于单药治疗组[(3.3±0.9) vs (2.1±0.6);(6.4±0.8) vs (4.5±0.5), 均P<0.01]。虽然SF-MPQ总分减分值两组间无统计学差异,但在疼痛情感维度方面,于治疗后第8、12周,合并治疗组减分值显著高于单药治疗组[(4.2±1.3) vs (2.3±1.0);(6.8±2.9) vs (4.6±1.7), 均P<0.01]。结论:合用度洛西汀与硫酸吗啡缓释片治疗癌痛的疗效优于单用硫酸吗啡治疗,且耐受性好。

关键词: 癌症, 吗啡, 疼痛, 度洛西汀, 疗效, 耐受性

Abstract: AIM: In order to provide a good reference for clinical treatment, the efficacy and tolerability of Duloxetine plus Morphine sulfate with a single morphine treatment in cancer pain management were compared.METHODS: One hundred and eighty patients with moderate to severe cancer-related pain were enrolled in this randomized, open-label, 12-week clinical study. Subjects were assigned to either a single therapy group (Morphine sulfate sustained release tablet, 100-200 mg/day) or a combined therapy group (same dose of Morphine sulfate sustained release tablet plus Duloxetine 30 mg/day for the first 2 weeks and 60 mg/day thereafter). The follow-up was performed at the baseline and the end of the 4th- , the 8th- and the twelfth-week respectively. Short-Form McGill Pain Questionnaire (SF-MPQ) and the 10-point visual analog scale (VAS) were used to assess the severity of pain. Depressive and anxiety symptoms were assessed using the Hamilton rating scale for depression and Hamilton rating scale for anxiety. The treatment emergent symptom scale and dropout rate were recorded to evaluate the tolerability.RESULTS: A similar dropout rates were noted in the single treatment arms compared to combined treatment arms (8.9% at 4 weeks, 15.6% at 8 weeks and 23.3% at 12 weeks vs 10.0% at 4 weeks, 17.8% at 8 weeks and 25.6% at 12 weeks, all P>0.05). Adverse events such as constipation, sudation and palpitation were higher in the combined treatment group than the single treatment group,but no significant group difference was found. A group difference markedly appeared between combined therapy group and single treatment group in the total score decreases in VAS in week 4 and week 12 [(3.3±0.9) vs (2.1±0.6);(6.4±0.8) vs (4.5±0.5), P<0.01, respectively]. Although no statistical difference appeared in SF-MPQ total score change, higher score-decrease values were found in respect to the painful emotion dimension in combined treatment group as compared to the single treatment group in week 8 and week 12 [(4.2±1.3) vs (2.3±1.0);(6.8±2.9) vs (4.6±1.7), P<0.01, respectively].CONCLUSION: Duloxetine plus Morphine sulfate sustained release tablet is superior to single Morphine sulfate sustained release tablet in the treatment of cancer-related pain in efficacy and has a good tolerability.

Key words: Cancer, Pain, Morphine, Duloxetine, Efficacy, Tolerability

中图分类号:

R614

戴志远, 郑芳, 李德强. 度洛西汀与硫酸吗啡联合治疗癌痛的临床观察[J]. 中国临床药理学与治疗学, 2013, 18(10): 1138-1143.

DAI Zhi-yuan, ZHENG Fang, LI De-qiang. Clinical trial in the relief of cancer pain in a combined therapy by Duloxetine plus Morphine sulfate[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(10): 1138-1143.

参考文献

[1] Tagányi K. Management of lung cancer-related pain [J]. Orv Hetil, 2011, 152(30):1184-1191.
[2] Laird B, Colvin L, Fallon M. Management of cancer pain: basic principles and neuropathic cancer pain [J]. Eur J Cancer, 2008, 44(8):1078-1082.
[3] Koller A, Miaskowski C, De Geest S, et al. A systematic evaluation of content, structure, and efficacy of interventions to improve patients' self-management of cancer pain [J]. J Pain Symptom Manage, 2012, 44(2):264-284.
[4] Turabi A, Plunkett AR. The application of genomic and molecular data in the treatment of chronic cancer pain [J]. J Surg Oncol, 2012, 105(5):494-501.
[5] Vadalouca A, Raptis E, Moka E, et al. Pharmacological treatment of neuropathic cancer pain: a comprehensive review of the current literature [J]. Pain Pract, 2012, 12(3):219-251.
[6] Rana SP, Ahmed A, Kumar V, et al. Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration [J]. Indian J Palliat Care, 2011, 17(2):162-165.
[7] Nakagawa S, Okamoto Y, Tsuneto S, et al. Can milnacipran used for neuropathic pain in patients with advanced cancer cause neuromuscular and somatosensory disorders [J]?J Palliat Med, 2011, 14(4):403-405.
[8] Arimura T, Hosoi M, Tsukiyama Y, et al. Pain questionnaire development focusing on cross-cultural equivalence to the original questionnaire: the Japanese version of the Short-Form McGill Pain Questionnaire [J]. Pain Med, 2012, 13(4):541-551.
[9] 张明园. 精神科评定量表手册[M]. 2版.长沙: 湖南科学技术出版社, 2003: 197-202.
[10] Manchikanti L, Manchikanti KN, Pampati V, et al. Prevalence of side effects of prolonged low or moderate dose opioid therapy with concomitant benzodiazepine and/or antidepressant therapy in chronic non-cancer pain [J]. Pain Physician, 2009, 12(1):259-267.
[11] McGeeney BE. Adjuvant agents in cancer pain [J]. Clin J Pain, 2008, 24 Suppl 10:S14-S20.
[12] Bajwa ZH, Simopoulos TT, Pal J, et al. Low and Therapeutic Doses of Antidepressants are Associated with Similar Response in the Context of Multimodal Treatment of Pain [J]. Pain Physician, 2009, 12(5):893-900.
[13] Kroenke K, Theobald D, Wu J, et al. The Association of Depression and Pain with Health-Related Quality of Life, Disability, and Health Care Use in Cancer Patients [J]. J Pain Symptom Manage, 2010, 40(3): 327-341.
[14] Nayebi AM, Rezazadeh H, Parsa Y. Effect of fluoxetine on tolerance to the analgesic effect of morphine in mice with skin cancer [J]. Pharmacol Rep, 2009,61(3):453-458.
[15] Laux G. Possibilities and limitations of psychopharmacological treatments in patients with psychological comorbidity [J]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2011, 54(1):37-45.