Prescribing trends and pattern of tramadol in Korea : analysis of 11-year Korean national health insurance database

국문 초록 (Abstract)

서론: 트라마돌은 중추적으로 작용하는 합성 진통제로서 mu-opioid 수용체에 대한 약한 효현 작용과 norepinephrine과 serotonin의 재흡수를 억제하는 작용이 복합적으로 작용하여 진통 효과를 나타내는 것으로 추정된다. 이 연구는 트라마돌의 처방 트렌드와 패턴을 분석하고 처방 요인을 제시하였다.
방법: 본 연구는 2003 1월 1일 부터 2013 12월 31까지의 건강보험심사평가원의 표본자료를 활용하여 의료기간을 외래로 방문하고 트라마돌을 1회 이상 처방 받은 비암성 통증 환자를 대상으로 하였다. 분석 대상인 트라마돌 약물은 약제 급여 목록을 활용하여 트라마돌, 트라마돌 서방형, 트라마돌 아세타미노펜을 포함하였다. 또한 NSAIDs 약물과 opioid약물등을 포함시켜 트라마돌의 처방 양상, 요인과 비교하였다.
결과: 2003년, 2007년, 2013 년의 각 그룹의 절대적 차이와 상대적 차이가 비교 분석되었다. 2003년에는 2,476 (19,9%) 명이였던 환자 수가 2007년에는 9,032 (26.4%)로 증가하였으며 2013년에는 124,594 (33.3%) 로 절대적 차이와 상대적 차이가 모두 크게 증가하였다. 통증 별로 분석한 결과 등 통증과 관절 통증 두개의 통증이 트라마돌 군에서 눈에 띄게 쓰이는 것을 알 수 있었다. 통증 별로 분석 시에는 트라마돌이 처방 된 2003~2007년 의 환자수와 2009~2013년의 환자수가 비교되었다. 관절 통증에 대하여 트라마돌이 처방된 환자수의 퍼센트는 44.4% 에서 68% 로 증가하였으며 등통증에 대하여는 51.7%에서 78.7%로 증가하였다. NSAIDs 약물과 비교 하여 처방 요인적 측면에서 보았을 때 통계적으로 유의미하였던 결과는 시외지역 (aOR: 1.34, 95% CI 1.32-1.36), 지방지역 (aOR: 1.64, 95% CI 1.61-1.66), 동시 처방 된 약물들 중 벤조다이아제핀 (aOR: 2.01, 95% CI 1.97-2.05) 와 프리가발린 (aOR: 3.28, 95% CI 2.95-3.64), 통증들 중 관절통(aOR: 3.08-3.18) 과 등 통증 (aOR: 6.24, 95% CI 6.09-6.39), 3차 병원 (aOR:3.08, 95% CI 3.00-3.17), 종합 병원 (aOR: 2.87, 95% CI 2.81-2.93), 동반질환에서는 우울증 (aOR: 1.56, 95% CI 1.49-1.62) 와 편두통 (aOR: 1.53, 95% CI 1.85-1.94) 그리고 CCI 점수 1점 (aOR: 1.48, 95% CI 1.46-1.51), 2점 (aOR: 1.89, 95% CI 1.85-1.94), 3점 이상 (aOR:2.13, 95% CI 2.07-2.19) 이였다.
결론: 본 연구는 2003년부터 2013년도의 비암성 통증 외래 환자들에 대한 트라마돌 처방 패턴, 트랜드와 요인을 분석하였다. 본 연구는 트라마돌 처방의 폭발적 증가를 수치화 하였으며 처방요인을 NSAIDs를 처방받은 환자와 마약성 진통제를 처방 받은 환자와 비교하여 오즈비를 산출하였으며 이 결과는 향후 트라마돌 관련 정책에 도움이 될 것으로 예상된다.

다국어 초록 (Multilingual Abstract)

Introduction: Tramadol is an analgesic drug that centrally acts as a weak Mu-opioid agonist with non-opioid mechanism of actions of inhibiting reuptake of norepinephrine and serotonin. This study demonstrated the prescribing trends and patterns of tramadol and indicated predictors of being prescribed tramadol
Method: Data was collected from Korean National Health Insurance Service Sample Cohort that included approximately 1 million subjects randomly extracted from the almost entire Korean population (50 million) by using national claims data from January 1, 2003 to December 31, 2013. Inclusion criteria of this study were patients in outpatient setting of all ages prescribed with NSAIDs at least once without history of having prescriptions for opioids and tramadol, prescribed with tramadol at least once without history of having prescriptions for opioids, and prescribed with opioids at least once. Exclusion criterion was history of any forms of cancer. (ICD-10: ‘C00’ – ‘C97’) and patients in inpatient setting.
Result: The absolute changes and relative changes of the study groups over the selected years (2003, 2007, 2013) were analyzed with the number of patients in each group. In 2003, numbers of patients with included drugs in the study were 2,476 (19.9%) for tramadol, 814 (6.5%) for opioids, and 9,163 (73.6%) for NSAIDs. Numbers of patients with tramadol, opioids, and NSAIDs in 2007 were 9,032 (26.4%), 1,451 (4.2%), and 23,741 (69.4%), respectively. Lastly, in 2013, numbers of patients in each drug groups were 124,594 (33.3%) for tramadol, 6,598 (1.8%) for opioids, and 242,870 (64.9%) for NSAIDs. Two prominent pain diagnoses in tramadol group patients were arthritis and back pain. In arthritis pain, the changes of utilization percentages from 2003-2007 to 2009-2013 of study drugs were 44.4% to 68.0%, 1.3% to 2.7%, and 54.4% to 29.3% in tramadol group, opioids group, and NSAIDs group, respectively. In back pain, the changes of utilization percentages from 2003-2007 to 2009-2013 of study drugs were 51.7% to 78.7%, 3.6% to 3.1%, and 44.7% to 18.3% in tramadol group, opioids group, and NSAIDs group, respectively. Noticeable predictors in tramadol group patients when compared with NSAIDs group were urban area (aOR: 1.34, 95% CI 1.32-1.36), rural area (aOR: 1.64, 95% CI 1.61-1.66), co-prescribed medication of benzodiazepine (aOR 2.01, 95% CI 1.97-2.05) and pregabalin (aOR: 3.28, 95% CI 2.95-3.64), pain diagnosis of arthritis (aOR 3.08-3.18) and back pain (aOR: 6.24, 95% CI 6.09-6.39), tertiary hospital (aOR: 3.08, 95% CI 3.00-3.17), general hospital (aOR: 2.87, 95% CI 2.81-2.93), history of depression (aOR: 1.56, 95% CI 1.49-1.62) and migraine (aOR: 1.53, 95% CI 1.46-1.61), and CCI scores of 1 (aOR 1.48, 95% CI 1.46-1.51) , 2 (aOR: 1.89, 95% CI 1.85-1.94), and 3 or more (aOR: 2.13, 95% CI 2.07-2.19).
Conclusion: This study demonstrated thorough trends of patients with tramadol prescription between 2003 and 2013 in outpatient setting. This study indicated explosive increased trend of prescribing tramadol and described possible characteristics of patients with tramadol prescription compared with patients with NSAIDs and opioids.

목차 (Table of Contents)

• Summary 9
• I. Background 11
• 1. Introduction 11
• II. Literature Review 13
• 1. High Use of Tramadol In Germany: an analysis of statutory health insurance data 13
• 2. Rising Opioid Prescribing in Adult U.S Emergency Department Visits: 2001-2010 13
• 3. Potentially Inappropriate Medication in Elderly Outpatients 14
• III. Objective 15
• IV. Method 16
• 1. Data Source 16
• 2. Study Subjects 16
• 3. Exposure Assessment 18
• 4. Overall Number of Study Patients with Selected Indications 21
• 5. Demographic Characteristics of Patients in the Study 23
• 6. Definitiona of Variables in the Study 24
• 7. Statistical Analysis 25
• V. Results 27
• 1. Trends of Prescribing Tramadol, NSAIDs, and opioids 27
• 2. Prescribing Trends of Tramadol, NSAIDs, and Opioids by Types of Pain 30
• 3. Demographic and Clinical Characteristics of Groups in the Study 32
• 4. Predictors of being in tramadol group compared with being in other study group 37
• VI. Discussion 42
• VII. Conclusion 45
• VIII. References 46
• IX. Abstract in Korean 50