應用新的診斷標準作華人纖維肌痛症治療時Pregabalin劑量反應之研究

Dose-response of Pregabalin for Treatment of Chinese Patients with Fibromyalgia under New Diagnostic Criteria

研究目的：本研究之目的，在評估本院疼痛科門診纖維肌痛症之華人病患，使用不同劑量之 Pregabalin治療時的止痛效果。方法：本研究選擇了22位有慢性嚴重疼痛且長期規律性於本院疼痛門診治療之病患，以開放標記方式使用Pregabalin治療作臨床試驗。所有病患均須符合美國風濕病醫學會纖維肌痛症診斷標準更新版（Wolfe et al，2011）的要求。在研究前的評估後（訪查1），病患均以Pregabalin150，300及450mg/d的劑量作三階段依每週增加一個劑量之方式，調整至病患有效止痛為止，然後按有效之劑量繼續治療至完成為期三週時間之研究。療效之評估是分別依使用Pregabalin的第一週（訪查2）、第二週（訪查3）及第三週（訪查4）結束時 進行。評估內容包括：疼痛嚴重程度評估（NRS）（0-10分）；睡眠品質量表（0-10分）；病患 整體改善量表（PGIC）（1-7分）及的纖維肌痛症綜合問卷（FIQR-2009）（0-100分）。同時，我們還評估其治療之滿意度（0-4分）及副作用等。另外，我們把有效之反應個案定義為能達到50%或以上之疼痛緩解者謂之。同時也所得之不同劑量之有效反應個案分成三組： 第一組為全程對Pregabalin 150mg/天有效者；第二組為對300mg/天有效者及第三組只對 450mg/天有反應者。所得之數據以平均值±標準差表示，並以Wilcoxon signed rank test、Kruskal-Wallis test及Dunn's post-hoc作統計分析，p value小於0.05為統計上有顯著之差異。結果：在給予Pregabalin治療的22位有效病患中，除其中一位未達50%有效疼痛緩解標準及2位因嚴重暈眩至無法繼續進行研究外；共有19位定為有效個案並完成本研究。在此19位個案中有15位為女性、4位為男性；平均年齡為48.1±7.5歲；廣泛分佈性疼痛指標（WPI分數）為8.2±1.7；症狀嚴重度（SS分數）為7.7±2.2；至於其發病時間長短為11.1±9.2年。其他所有於治療前、後之數據均以Mean±SD表示，包括：壓痛點數目、疼痛分數、睡眠品質分數、纖維肌痛症綜合問卷分數、病患整體改善量表分數及滿意度等。終結所有有效個案中，有11位屬於第二組（300mg/天）、6位屬於第三組（450mg/天）及只有2位屬第一組（150mg/天）。其間第二、三組治療前後之疼痛分數、睡眠品質分數、纖維肌痛症綜合問卷分數等之改善及壓痛點數目之減少，均有顯著之差異（p<0.05）。在各組間的比較中， 第二、三組間大置上沒有明顯之差異；只有第一組於纖維肌痛症綜合問卷分數及滿意度與第二、三組，及於疼痛分數、病患整體改善量表分數與第三組有顯著差異外，其餘均無差異。至於不良副作用則以暈眩、體重增加及嗜睡為主，而第三組比第二組為常見。結論：除Pregabalin可有效地緩解大部分纖維肌痛症的慢性頑固性疼痛，同時可改善病人的睡眠及生活品質；而300mg/天比450mg/天劑量更常出現於華人病患為有效治療劑量，同時有較少的副作用。

Objective: The purpose of this study was to assess the efficacy for different doses of Pregabalin in the treatment of Chinese patients with Fibromyalgia (FM) in our Pain Clinic. Methods: This open-label, 3 week clinical trial of Pregabalin was done on 22 2013;23(2): 45 ~ 52) patients with FM who underwent long-term treatment for chronic intractable pain. Their symptoms met the modified American College of Rheumatology diagnostic criteria for FM by Wolfe et al 2011. After a pre-study patient assessment (visit 1), we Key Words: titrated Pregabalin at doses of 150, 300, and 450 mg/d, increasing weekly, until effective for pain relief without intolerable adverse effects. Then we maintained the effective dose for the remainder of the 3-week treatment course. Patients were Pregabalin, assessed at the end of each week (visit 2,3,4). Outcome Measures included a verbal ranking scale for pain intensity (NRS) (0-10); quality of sleep (0-10); Patient Global Impression of Change (PGIC) (1-7); and the Revised Fibromyalgia Impact Dose-response. Questionnaire (FIQR-2009)(0-100). We also recorded patient satisfaction (0-4) and adverse effects. The criteria of responders means the patient reached 50% or more pain relief. We divided our patients into three groups: Group I: overall responded to Pregabalin150 mg/d, Group II: responded to 300 mg/d, and Group III: responded to 450 mg/d only. Data was presented as mean E standard deviation (SD) and analyzed by Wilcoxon signed rank test and Kruskal-Wallis test with a Dunn's post-hoc test, and p<0.05 considered statistically significant. Results: Twenty of the 22 patients enrolled in this study reported effective pain relief, but one did not reach the criteria of responders and two withdrew due to experiencing intolerable dizziness. Among the 19 effective cases, 15 were female and 4 were male, with average age of 48.1±7.5 years. Widespread Pain Index was 8.2±1.7; Symptom Severity score was 7.7±2.2; the duration of FM was 11.1±9.2 years. All data showed a mean±SD, before and after treatment, included number of tender points, pain score, quality of sleep, FIQR-2009 score, PGIC score and overall satisfaction. However, 11 cases concluded in Group II (300 mg/d) and 6 cases in Group III (450 mg/d), but only 2 cases in Group I (150 mg/d). There was significant improvement in pain score, quality of sleep, FIQR-2009 score and significant reduced tender points for Groups III and III (p<0.05). There were no significant differences between Groups II and III for number of tender points, pain score, quality of sleep, FIQR-2009 score, PGIC score and overall satisfaction, except Group I had significant difference for FIQR-2009 score and overall satisfaction with Groups II and III; but only significant difference in pain score and PGIC score with Group III. The common adverse effects were dizziness, weight gain and somnolence, but more frequent occulted in Group III than Group II. Conclusions: Pregabalin is found to effectively relieve chronic intractable pain of FM. It can also improve the quality of sleep and life. The 300 mg/d is the more commonly effective dose for Chinese patients than 450 mg/d with less adverse effects.