- 學位論文
以統合分析比較5% lidocaine medicated plaster與pregabalin對於帶狀皰疹後神經痛之療效與安全性(實證醫學)
Efficacy and safety of 5% lidocaine medicated plaster in comparison with pregabalin in postherpetic neuralgia by meta-analysis. (Evidence-Based Medicine)
摘要
研究背景：帶狀疱疹(Herpes zoster)是中年人常見的疾病或痛症，當帶狀疱疹的紅疹或水泡消失後，若疼痛仍持續1個月以上，則稱為帶狀疱疹後神經痛 (Postherpetic neuralgia, PHN)。近年來帶狀皰疹後神經痛患者人數不斷的攀升，帶狀疱疹後神經痛是種難以忍受、持續或不定時發作的強烈疼痛，若沒有即時治療，可能嚴重影響病人的生活品質。研究目的：由於目前衛生福利部核准之治療帶狀皰疹後神經痛之藥物為5% Lidocaine medicated plaster、Gabapentin或Pregabalin。而本研究要討論的Pregabalin與5% Lidocaine medicated plaster是臨床上較常使用於治療帶狀皰疹後神經痛的兩種藥物，兩者同時也是被歐盟推薦為第一線使用於治療帶狀皰疹後神經痛之首選藥物。所以，我們期望能透過實證醫學的方法，將證據等極高的文獻，統整相同主題不同結果的文獻，探討整理療效、疼痛分數的下降情形比較其治療效果以及兩者的安全性比較。讓在繁忙的臨床工作中的醫護人員，能夠快速取得文獻的結論，提供最佳證據等級以運用醫療決策於病人身上，幫助患者對於治療用藥選擇有所依據，以期患者得到最適當的治療。 研究方法：本研究研究方法是以實證醫學(Evidence-Based Medicine，EBM)手法進行，本研究利用統合分析(Meta-analysis)的方式來評估Pregabalin與5% Lidocaine medicated plaster的療效和安全性。利用MEDLINE及PUBMED等資料庫進行搜索，納入關鍵字Lidocaine and Pregabalin and Postherpetic neuralgia並限制條件為隨機控制試驗(RCT-Randomized Controlled Trial)去作交集搜尋，評讀後再利用嚴格的納入條件(Inclusion)和排除條件(Exclusion)標準來挑選，最後是由38篇中挑選出5篇符合條件的文獻，以軟體RevMan進行統合分析，再利用森林圖(Forest plot)、漏斗圖(Funnel plot)的解讀，來加以探討整理療效、疼痛分數的下降情形比較其治療效果以及兩者的安全性比較。研究結果： 研究結果顯示，在療效的部分，大多結果是使用兩種藥物效果是無差異的，無差異的評估指標量表為以下5種: 1.NRS-3疼痛分數的改善效果(Change in NRS-3 score from baseline)。 2.NRS-3疼痛分數的改善≥30%者效果(Reduction in NRS-3 score of ≥30% from baseline)。 3. 在神經病理性疼痛症狀量表中的灼熱感改善效果(NPSI change from baseline in presence of Burning pain)。 4.神經病理性疼痛症狀量表中的刺痛感改善效果(NPSI change from baseline in presence of Stabbing pain)。 5. 神經病理性疼痛症狀量表中的痛如針扎感的改善效果(NPSI change from baseline in presence of pins and needles like pain)，其中較少數療效是有差異的(療效評估結果是Pregabalin組的效果是優於5% Lidocaine medicated plaster組)的評估指標量表為以下3種: 1.前四週的反應率、2.在NRS-3疼痛分數的改善≥50%者效果、3.在觸摸痛嚴重程度量表效果。另外，在不良反應的結果比較中，研究結果顯示，在安全性的部分，大多結果是使用5% Lidocaine medicated plaster的確是有較高的安全性，如: 1.不良反應人數比較、2.藥物相關的不良反應次數比較、3.產生與藥物相關的不良反應人數比較、4.由於不良事件停藥數比較、5.藥物相關的不良事件而停藥數比較、患者最常見的藥物相關的不良事件-6.頭暈、7.疲倦、 8.嗜睡、9.頭痛、10.眩暈。 而其中效果評估結果是Pregabalin較5% Lidocaine medicated plaster組有較高的安全性的評估結果為以下3種: 1.產生嚴重不良反應數比較、2.因為藥物而產生嚴重不良反應數比較、 3.患者最常見的藥物相關的不良事件-應用部位刺激比較。討論：在尚未進行本研究前，進行文獻評讀工作時，將所蒐集到的4篇文獻加以評讀，一篇文獻研究結果表示，在PHN的患者，Pregabalin組的治療效果優於5% Lidocaine medicated plaster組;但在另三篇文獻研究結果卻表示， 5% Lidocaine medicated plaster組的治療效果優於Pregabalin組的。但在本研究，將4篇的數據以統計軟體RevMan加以統整、加權後，所得出的研究結果顯示，在療效的部分，大多結果是使用兩種藥物效果是無差異的。由此而知，在經由統計軟體RevMan加以統整、加權後，所得出的研究結果顯示，是與預期結果不同的，這就是實證醫學的奧妙與迷人之處，我們可以透過實證醫學的方法，統整相關文獻，讓在繁忙的臨床工作中的醫護人員，能夠快速取得文獻的結論，提供最佳證據等級以運用醫療決策於病人身上。
並列摘要
Background: Herpes zoster is a common disease in middle age, when the rash or blisters disappear, if pain persists a month or more, it is called postherpetic neuralgia (PHN). Post-herpetic neuralgia in recent years, the number of patients has been rising, post-herpetic neuralgia is a kind of unbearable, sustained or intense episodes of pain from time to time, if not immediately treated, may seriously affect the quality of life of patients. Objective:Because the current DOH approval of drugs to treat postherpetic neuralgia is 5% Lidocaine medicated plaster, Gabapentin or Pregabalin. Pregabalin and 5% Lidocaine medicated plaster is most commonly used in the treatment of post-herpetic neuralgia, both of Pregabalin and 5% Lidocaine medicated plaster is also recommended as a first-line to treatment of post-herpetic neuralgia in EU. So, we can expect through the methods of evidence-based medicine, document integration of different results, discussion on the efficacy, pain scores to compare the effectiveness and safety. Let medical staff in a busy clinical work, can quickly obtain literature concluded to provide the best level of evidence, to use the medical decision-making in patients, to help patients choose some basis for drug treatment to patients receive the most appropriate treatment.Methods:The method of this paper based on evidence-based medicine (EBM)We use meta-analysis to assess the efficacy of Pregabalin with 5% Lidocaine medicated plaste. We used database search, ex: MEDLINE and PUBMED etc., included in the keyword Lidocaine and Pregabalin and Postherpetic neuralgia and limiting conditions for the RCT-Randomized Controlled Trial, reuse criteria for inclusion and exclusion criteria to select,Finally, from the 38 to pick out five qualified literature, we use software RevMan to meta-analysis, and use of forest plot, Explanation funnel plot to compare the efficacy and safety. Results:The results showed that in some efficacy, most results were obtained using the two drugs is no difference in effect (1. Change in NRS-3 score from baseline, 2. Reduction in NRS-3 score of ≥30% from baseline, 3. NPSI change from baseline in presence of Burning pain, 4. NPSI change from baseline in presence of Stabbing pain, 5. NPSI change from baseline in presence of pins and needles like pain) . But, a smaller number of effect is different(1.Responders at week 4 , 2. Reduction in NRS-3 score of ≥50% from baseline , 3. Allodynia Severity rating scale). In addition, the result of the comparison of adverse events, the researchers showed that, in the security section, most of the results is to use 5% Lidocaine medicated plaster is more security (1.Number of patients with AEs, 2. Number of drug-related AEs, 3.Number of patients with drug-related AEs, 4. Discontinuations due to AEs,5.Discontinuations due to drug-related AEs , Number of patients with most common drug-related AEs-6. Dizziness, 7. Fatigue, 8.Somnolence, 9. Headache, 10. Vertigo). Conclusions：In previous research has not yet started, Comment on reading literature, Review of literature to read 4, a literature study: PHN patients, the treatment effect Pregabalin group than 5% Lidocaine medicated plaster group; But on the other three literature results show, treatment 5% Lidocaine medicated plaster group than Pregabalin group. However, in this study, statistics 4 literature, research results obtained show in some effect, most results were obtained using two drugs effect is no different. Thus, after the RevMan statistics, the results are different from expected results, and this is the mystery and charm of evidence-based medicine, We can through the method of evidence-based medicine, Integration literature, let the medical staff in a busy clinical work, it is possible to quickly obtain conclusions literature to provide the best level of evidence, to the use of medical decision-making in the patient.