臺灣博碩士論文加值系統

【背景】
檳榔是名列全世界第四常見的合法濫用物質，其成癮危害盛行於東南亞各國以及南島語系各個國家。過往的研究多著重在檳榔內含生物鹼如檳榔鹼跟檳榔次鹼對於人體的毒害性，對於其成癮機制較少有研究提及；由於文獻回顧發現檳榔的檳榔鹼成分對於細胞實驗中的單胺氧化酶有減低其核甘酸(mRNA)以及蛋白質(protein)表現的狀況，部分基礎研究並且指出檳榔活性成分可能具有抗憂鬱劑的機轉。由於目前並沒有藥物可以治療檳榔成癮，本論文假設檳榔成癮可以透過抗憂鬱劑治療來達成戒癮的目的，並且降低檳榔使用失調患者每日嚼食檳榔顆數以及每周嚼食天數。
【方法】
研究共招募111名符合本研究設計的檳榔使用失調患者，進入雙盲隨機分配以及安慰劑對照的八周藥物試驗，檳榔使用失調患者以美國精神科統計與診斷手冊第五版來做診斷，藥物試驗隨機分配為escitalopram 10mg/d、moclobemide 150mg/d以及安慰劑三組。我們並且在進入試驗前第0周、第2周、第4周、第6周與第8周追蹤以及評估患者的檳榔使用情形以及戒斷狀況。第0周以及第8周並且對患者有抽血追蹤生化值。
【結果】
本臨床試驗解盲後發現在moclobemide 150mg/d以及escitalopram 10mg/d兩組病人均在第6周開始顯著減少檳榔每天嚼食量以及頻率。物質使用嚴重程度量表以及渴求量表亦顯示在治療藥物組別中有顯著下降。而moclobemide組在治療六周跟八周後戒癮成功的累積發生率(cumulative incidences)為0.5跟0.58，escitalopram組為0.34跟0.47，高於安慰劑組的0.27跟0.43，P值為0.025有統計意義。
【討論】
本篇論文為全世界第一篇針對檳榔成癮的藥物治療雙盲隨機分配以及安慰劑對照臨床試驗，結果顯示兩種抗憂鬱劑：「選擇性血清素再回收抑制劑」以及「單胺氧化劑抑制劑」在固定劑量以及持續治療至少6周，可以顯著降低檳榔使用失調患者每日檳榔嚼食量以及每周嚼食天數。由於本研究受限於樣本數少，以及試驗藥物的固定劑量以及時間，所以對於更廣泛的族群數，或是藥物治療最高劑量以及時間均有其研究侷限性，未來需要更多的合作研究來開發檳榔成癮的戒斷治療模式。

Background:
Betel-quid (BQ) is ranked as the fourth most popular abused substance in the worldwide. People are vulnerable in the abuse and dependence of BQ in the South-Eastern Asia and Austronesian countries. Past studies focus on the lethal effects related to the arecoline and arecaidine of the BQ alkaloid. Few researches note the addictive property of BQ. Some papers indicate that BQ alkaloid showed the effects of monoamine oxidase down-regulation in mRNA and protein, thus BQ might possess the mechanism of antidepressant. Since no medication exist as the therapeutic drug for BQ addiction, we hypothesized that antidepressant could assist in the abstinence of BQ addiction by reducing the daily consuming BQ amount and decreasing the using days weekly.
Method：
We recruited 111 patients diagnosed as the betel-quid use disorder (BUD). They were allocated into the eight-week double-blinded and placebo-controlled clinical trial. We made the BUD diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). There are three groups including escitalopram 10mg/d, moclobemide 150mg/d, and placebo consisting the clinical trial. We followed up the consuming condition of BQ and the status of abstinence before they entered the trial (W0), the 2nd week (W2), the 4th week (W4), the 6th week (W6), and the 8th week (W8). We obtained the blood test on W0 and W8.
Results：
After unblind, we found that the patients in the groups of moclobemide 150mg/d and escitalopram 10mg/d began to decrease their consuming amount and frequency since W6, with statistical significance. The cumulative incidences of BQ cessation rates in the group moclobemide are calculated 0.5 and 0.58 in W6 and W8, escitalopram 0.34 and 0.47, while placebo 0.27 and 0.43. P-value was estimated as 0.025 with statistical significance.
Discussion：
The paper is the first double-blinded and placebo-controlled clinical trial in the world to study the cessation drug of BQ addiction. The conclusion was revealed that two kinds of antidepressant including the “selective serotonin re-uptake inhibitor” and “monoamine oxidase inhibitor” in fixed dosage and treatment duration could lower down the consuming amount and frequency of BQ use. Our study was limited in the small sample size. In addition, it was also constrained from the fixed medication dosage and the therapeutic time. More studies are needed for more advanced consensus of medication therapy of BQ addition.

誌謝辭(DEDICATION) 8
中文摘要(CHINESE ABSTRACT) 9
ENGLISH ABSTRACT 10
圖目次(LIST OF FIGURES) 12
表目次(LIST OF ILLUSTRATIONS) 13
正文(BODY OF THE THESIS) 14
(一) 緒論 14
1. 背景 14
2. 檳榔成癮的流行病學 15
3. 檳榔成癮的神經精神分子機轉 15
4. 檳榔戒癮的研究文獻回顧 15
5. 檳榔成癮戒斷藥物治療假設 16
(二) 研究目的 16
(三) 研究方法 17
1. 檳榔成癮診斷準則標準 17
2. 研究病人收案納入以及排除標準 17
3. 臨床試驗藥物雙盲以及對照組之標準程序(the SOP procedure of double-blinded, placebo-controlled and randomized clinical trial) 18
4. 統計方法 19
(四) 結果 21
1. 臨床試驗病人開始試驗治療前基本資料分析以及分組概況 21
2. 檳榔使用疾患臨床藥物試驗戒癮預後指標 21
(五) 討論 24
(六) 結論 25
(七) 未來展望 26
參考書目與參考文獻( BIBLIOGRAPHIES/REFERENCES) 37

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