fm

한국임상약학회지제 25 권제 3 호 Korean J Clin Pharm, Vol. 25,. 3, 2015 Original Article Korean Journal of Clinical Pharmacy Official Journal of Korean College of Clinical Pharmacy Available online at http://www.kccp.or.kr pissn: 1226-6051 노인입원환자의비암성통증에대한약물처방현황 남기남 1,2 최은옥 1,2 김범해 1,2 성새라 2 허유정 2 이경주 2 이유정 2 * 1 강원대학교병원약제과, 2 강원대학교약학대학 (2015년 4월 16일접수 2015년 6월 30일수정 2015년 7월 10일승인 ) Prescribing Patterns of Pain Medication in Hospitalized Elderly Patients with n-cancer Pain Ki Nam Nam 1,2, Eun Ok Choi 1,2, Beam Hae Kim 1,2, Sae Ra Seong 2, Yoo Jeong Heo 2, Kyeong Ju Lee 2, and Yu Jeung Lee 2 * 1 Department of Pharmacy, Kangwon National University Hospital, Chuncheon-si, Gangwon-do 200-722, South Korea 2 College of Pharmacy, Kangwon National University, Chuncheon-si, Gangwon-do 200-701, South Korea (Received April 16, 2015 Revised June 30, 2015 Accepted July 10, 2015) ABSTRACT Objective: Pain is very common in the elderly, so there is a high prevalence of analgesic use among this population. The purpose of this study was to assess patterns of analgesic use and evaluate factors associated with analgesic use in elderly patients. Method: The subjects of this study were patients over 65 years old hospitalized in a teaching hospital located in Chuncheon-si, Korea between January 1, 2014 and March 31, 2014. Data collection regarding analgesic prescriptions and baseline characteristics was conducted using computerized hospital database by medical information team. Logistic regression analysis was used to identify factors related to analgesic use. Results: A total of 2,394 patients were finally included. Among these patients, 700 (29.2%) took analgesics; 521 (74.4%) out of these 700 patients were received opioid analgesics and 179 (25.6%) were received only nonopioid analgesics. The most frequently prescribed opioid analgesic was pethidine (45.7%), and the most frequently prescribed nonopioid analgesic was acetaminophen (44.1%). Fracture was associated with increased odds of opioid analgesic prescriptions (OR = 2.766, 95% CI = 2.019-3.790, p < 0.001) and any analgesic prescriptions (OR = 2.394, 95% CI = 1.766-3.244, p < 0.001). Stroke or cerebral infarction was associated with decreased odds of opioid analgesic prescriptions (OR = 0.636, 95% CI = 0.471-0.858, p = 0.003). Conclusion: A significant proportion of hospitalized elderly patients use analgesics. Health care professionals should consider factors associated with analgesic use in this population to improve pain management. KEY WORDS: pain, analgesics, opioids, elderly, management 인간의평균수명은전세계적으로남성은 1990년 62.8세에서 2010년 67.5세, 여성은 1990년 68.1세에서 2010년 73.3세로연장되고있으며, 대한민국의경우도남성은 1990년 68.1세에서 2010년 78.8세, 여성은 1990년 72.2세에서 2010년 82.7세로연장되고있다. 1) 이러한평균수명의연장은각종질환을가진노인환자수의증가로이어진다. 통증은흔하게발생하는증상이며, 특히노인환자의경우골다공증, 류마티스관절염등근골격계질환을가진경우가많아통증발생비율이상당히높다. 2,3) 고령사회가되면서만성통증으로심한통증을호소하는성인은유럽에서 19% 에이르며, 4) 이러한통증을조절하기위하여노인환자에게있어 진통제사용이점차증가하고있다. 5) 2013 년미국에서발표한연구에의하면, 한요양시설의환자 2500명중 77% 가정기적으로진통제처방받았다. 6) 환자가심각한인지장애, 85세이상의나이, 또는파킨슨병환자일경우진통제처방이감소한다는보고가있다. 한편, 골절과당뇨병이있을경우진통제처방이증가한다는보고도있다. 6,7) 통증의관리를위해서많이처방되는마약성진통제는만성통증에있어강력한진통효과를갖고있으나, 중독이나오남용, 약물이상반응등의위험성도가지고있으므로통증관련지침에따른적절한약물의선택이필요하다. 8) 또한, 노인환자에게있어불충분한통증관리는신체기능적장해와같은물 *Correspondence to: Yu Jeung Lee, Department of Clinical Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon-si, Gangwon-do 200-701, South Korea Tel: +82-33-250-6913, Fax: +82-33-255-7865 E-mail: yujeung@kangwon.ac.kr 145

146 / Korean J Clin Pharm, Vol. 25,. 3, 2015 리적부분뿐만아니라우울이나불안등정신적부분까지도영향을미칠수있다. 9) 그러나국내에서는지금까지노인환자의진통제처방현황에대한연구는매우제한적이다. 따라서, 본연구는노인환자들의진통제처방현황을분석하고, 진통제처방에영향을미치는관련인자들을분석하고자하였다. 연구방법 연구대상본연구는 2014년 1월 1일부터 2014년 3월 31일사이에강원도춘천시에위치한 500병상규모의 2차국립의료기관인강원대학교병원에입원한만 65세이상노인환자를대상으로하였으며, 제외기준은암환자로하였다. 자료수집방법강원대학교병원의료정보팀에의뢰하여 2014년 1월 1일부터 2014년 3월 31일까지입원한환자들의자료를받았다. 입원기간동안진통제처방기록이있는환자와없는환자로분류하였으며, 진단명에암성상병코드가있는환자는제외하였다. 연구대상환자의성별, 나이, 동반질환 ( 골절, 골다공증, 치매, 우울증, 파킨슨병, 뇌졸중또는뇌경색, 당뇨병, 심부전, 신부전, 만성폐쇄성폐질환 ), 진통제처방내역을조사하였다. 한환자내에서입원기간동안가장많은종류의진통제를처방받은일자를표본일로하였으며, 표본일에동일성분의진통제를여러번처방을받은경우에는한번으로간주하였다. 최소 2일이상연속적으로진통제를처방받은경우를진통제사용으로정의하였다. 본연구는피험자의안전과개인정보보호및연구자준수서약을포함한연구계획을강원대학교병원생명의학연구윤리심의위원회의승인을받아후향적으로실시되었다 (IRB File. KNUH-2015-05-004). 자료분석진통제처방환자는다시마약성진통제를처방받은환자와비마약성진통제를처방받은환자로분류하여진통제처방순위를분석하였다. 환자들이진통제를한종류만처방받는경우도있고, 두종류이상처방받는경우도있으므로, 이에대한비율도분석하였다. 전체진통제 ( 마약성진통제와비마약성진통제 ) 처방여부및마약성진통제처방여부에동반질환이미치는영향을분석하고자전체진통제처방군과미처방군, 마약성진통제처방군과미처방군에서의각동반질환의발생빈도를분석하였다. 동반질환여부는대상환자들각각의진단명을우선적으로고려하였다. 또한각환자들의기본 3개월동안의처방내역을검토하여관련질환을위한치료약물이처방되었는지검토하였다. 통계분석수집된자료의분석에는 SPSS version 12.0 (SPSS Inc. Chicago, USA) 통계프로그램을사용하였다. 진통제처방순위및처방현황은처방건수에대하여빈도분석을하였다. 전체진통제처방군과미처방군, 마약성진통제처방군과미처방군의나이비교는 unpaired t-test를시행하였고, 성별과각동반질환의발생빈도비교는 chi-squared test를시행하였다. 동반질환이진통제처방에미치는영향에대한분석은 logistic regression analysis를사용하였다. 통계적유의성은유의확률 (p-value) 이 0.05 미만일때로정의하였다. 연구결과 연구대상자의일반적특성 2014년 1월 1일부터 2014년 3월 31일까지암환자를제외하고강원대학교병원에입원한만 65세이상노인환자는총 2,394명이었다. 이중마약성진통제를처방받은환자는 521명이며, 마약성진통제처방을받지않고비마약성진통제만을처방받은환자는 179명으로, 전체진통제처방환자는 700명이었다. 전체연구대상자의평균연령은 76.3세이고, 전체진통제처방환자의평균연령은 76.2세이었다. 성별은전체연구대상자는여성이 52.7%, 전체진통제처방환자는여성이 54.7% 로여성환자의비율이다소높았다. 전체환자에서동반질환은심부전을가지고있는경우가 52.0% 로가장많았으며, 당뇨병이 26.7% 로두번째로많았다. 전체진통제처방환자에서도심부전을동반질환으로가지고있는경우가가장많았으며 (50.4%), 당뇨병 (25.4%) 이두번째로많았다. 진통제처방현황진통제의처방현황을분석한결과, 마약성진통제와비스테로이드성소염진통제를병용처방한경우가 14.4% 로가장많았으며, acetaminophen의단독처방은 2.1% 로가장적었다 (Table 1). 진통제처방순위는마약성진통제중에서 pethidine이 45.7% 로가장많았고, fentanyl이 33.2% 로두번째로많았다 (Table 2). 비마약성진통제의처방순위는 acetaminophen이 44.1% 로가장처방건수가많았으며, diclofenac이 18.6% 로두번째로많았다 (Table 3). 진통제처방에영향을미치는인자분석마약성진통제를처방받은환자군과미처방군은남성의비율이각각 42.8%, 48.6% 로성별에서통계적으로유의한차이가있었다. 동반질환으로는골절, 치매, 뇌졸중또는뇌경색, 당

노인입원환자의비암성통증에대한약물처방현황 / 147 Table 1. Prescribing patterns of all analgesics. Patterns Number of patients Percentage of patients Opioid only 85 3.6 Opioid + acetaminophen combination 92 3.8 Opioid + NSAID combination 344 14.4 NSAID only 129 5.4 Acetaminophen only 50 2.1 ne 1,694 70.8 Total 2,394 100.0 Table 2. Number of opioid analgesic prescriptions. Opioid analgesics Number of prescriptions #) Percentage of prescriptions Pethidine 430 45.7 Fentanyl 312 33.2 Codeine 80 8.5 Oxycodone 66 7.0 Morphine 32 3.4 Remifentanil 21 2.2 Total 941 100.0 #) If the same patient took more than one analgesic, each analgesic was calculated individually Table 3. Number of non-opioid analgesic prescriptions. n-opioid analgesics Number of prescriptions #) percentage of prescriptions Acetaminophen 135 44.1 Diclofenac 57 18.6 Propacetamol 28 9.2 Aceclofenac 26 8.5 Ketorolac 20 6.5 Zaltoprofen 16 5.2 Celecoxib 13 4.2 Talniflumate 5 1.6 Ibuprofen 3 1.0 Mefenamic acid 1 0.3 Piroxicam 1 0.3 Meloxicam 1 0.3 Total 306 100.0 #) If the same patient took more than one analgesic, each analgesic was calculated individually 뇨병에서두군간에통계적으로유의한차이가있었다 (Table 4). Multivariate logistic regression analysis를시행한결과, 골절이있는경우에없는경우에비하여마약성진통제를처방받을가능성이 2.766배이며 (OR = 2.766, 95% CI = 2.019-3.790, p < 0.001), 뇌졸중또는뇌경색이있는경우에는없는경우에 Table 4. Characteristics of patients who received opioid analgesic prescriptions. Total Opioid analgesic prescription p-value (n = 2,394) Yes (n = 521) (n = 1,873) Age, mean ± SD, year 76.3 ± 6.7 76.2 ± 6.6 76.4 ± 6.7 0.541 Sex, n Male 1,133 (47.3) 223 (42.8) 910 (48.6) 0.020 Female 1,261 (52.7) 298 (57.2) 963 (51.4) Fracture, n Yes 184 (7.7) 78 (15.0) 106 (5.7) < 0.001 2,210 (92.3) 443 (85.0) 1,767 (94.3) Osteoporosis, n Yes 118 (4.9) 27 (5.2) 91 (4.9) 0.819 2,276 (95.1) 494 (94.8) 1,782 (95.1) Dementia, n Yes 327 (13.7) 52 (10.0) 275 (14.7) 0.006 2,067 (86.3) 469 (90.0) 1598 (85.3) Depression, n Yes 234 (9.8) 39 (7.5) 195 (10.4) 0.055 2,160 (90.2) 482 (92.5) 1,678 (89.6) Parkinson's Disease, n Yes 74 (3.1) 13 (2.5) 61 (3.3) 0.397 2,320 (96.9) 508 (97.5) 1,812 (96.7) Stroke, Cerebral Infarction, n Yes 418 (17.5) 62 (11.9) 356 (19.0) < 0.001 1,976 (82.5) 459 (88.1) 1,517 (81.0) Diabetes Mellitus, n Yes 640 (26.7) 121 (23.2) 519 (27.7) 0.044 1,754 (73.3) 400 (76.8) 1,354 (72.3) Heart Failure, n Yes 1,245 (52.0) 261 (50.1) 984 (52.5) 0.346 1,149 (48.0) 260 (49.9) 889 (47.5) Renal Failure, n Yes 211 (8.8) 42 (8.1) 169 (9.0) 0.541 2,183 (91.2) 479 (91.9) 1,704 (91.0) COPD, n Yes 236 (9.9) 45 (8.6) 191 (10.2) 0.319 2,158 (90.1) 476 (91.4) 1,682 (89.8) SD (Standard Deviation); COPD (Chronic Obstructive Pulmonary Disease) 비하여마약성진통제를처방받을가능성이 0.636 배이었다 (OR = 0.636, 95% CI = 0.471-0.858, p = 0.003) (Table 5). 마약성진통제또는비마약성진통제를처방받은전체진통

148 / Korean J Clin Pharm, Vol. 25,. 3, 2015 Table 5. Results of multivariate logistic regression on factors associated with opioid analgesic prescriptions. OR (95% CI) p-value Sex Male 0.872 (0.713-1.067) 0.183 Female Fracture Yes 2.766 (2.019-3.790) < 0.001 Dementia Yes 0.786 (0.566-1.092) 0.151 Depression Yes 0.738 (0.511-1.068) 0.107 Stroke, Cerebral Infarction Yes 0.636 (0.471-0.858) 0.003 Diabetes Mellitus Yes 0.857 (0.680-1.080) 0.191 OR (Odds Ratio); CI (Confidence Interval) 제처방환자군과어떠한진통제도처방받지않은환자군은동반질환으로골절이있는경우가각각 12.6%, 5.7% 로통계적으로유의한차이가있었으며, 성별과연령, 다른동반질환에서는통계적으로유의한차이가없었다 (Table 6). Logistic regression analysis를시행한결과에서도골절이있는경우에진통제처방을받을가능성이 2.394배증가하는것으로나타났다 (OR = 2.394, 95% CI = 1.766-3.244, p < 0.001) (Table 7). 고찰및결론 본연구는만 65세이상의노인입원환자를대상으로진통제처방현황을파악하고, 진통제처방에영향을미치는인자들을분석하였다. 본연구의결과, 암환자를제외한만 65세이상의노인입원환자중 29.2% 가진통제를처방받았다. 이중비마약성진통제 (25.6%) 보다는마약성진통제처방 (74.4%) 의비율이더높았다. 마약성진통제는중추신경계에직접적으로작용하여 nociceptive signal( 통각수용기적신호 ) 를차단하여진통효과를나타내기때문에, 광범위한통증정도를효과가훨씬빠르고강하게관리할수있다. 따라서변비, 오심, 진정, 호흡저하에서부터내성과의존성에이르는부작용이있음에도불구하고, 10) 수술전 후통증관리뿐만아니라급 만성통증관리에효율적으로사용할수있어마약성진통제의처방비율이더높은것으로보인다. 11,12) Table 6. Characteristics of patients who received any analgesic prescriptions. Total Any analgesic prescription p-value (n = 2,394) Yes (n = 700) (n = 1,694) Age, mean ± SD, year 76.3 ± 6.7 76.2 ± 6.7 76.4 ± 6.7 0.661 Sex, n Male 1,133 (47.3) 317 (45.3) 816 (48.2) Female 1,261 (52.7) 383 (54.7) 878 (51.8) 0.208 Fracture, n Yes 184 (7.7) 88 (12.6) 96 (5.7) 2,210 (92.3) 612 (87.4) 1,598 (94.3) < 0.001 Osteoporosis, n Yes 118 (4.9) 43 (6.1) 75 (4.4) 2,276 (95.1) 657 (93.9) 1,619 (95.6) 0.096 Dementia, n Yes 327 (13.7) 87 (12.4) 240 (14.2) 2,067 (86.3) 613 (87.6) 1,454 (85.8) 0.267 Depression, n Yes 234 (9.8) 60 (8.6) 174 (10.3) 2,160 (90.2) 640 (91.4) 1,520 (89.7) 0.226 Parkinson's Disease, n Yes 74 (3.1) 24 (3.4) 50 (3.0) 2,320 (96.9) 676 (96.6) 1,644 (97.0) 0.604 Stroke, Cerebral Infarction, n Yes 418 (17.5) 113 (16.1) 305 (18.0) 1,976 (82.5) 587 (83.9) 1,389 (82.0) 0.287 Diabetes Mellitus, n Yes 640 (26.7) 178 (25.4) 462 (27.3) 1,754 (73.3) 522 (74.6) 1,232 (72.7) 0.361 Heart Failure, n Yes 1,245 (52.0) 353 (50.4) 892 (52.7) 1,149 (48.0) 347 (49.6) 802 (47.3) 0.323 Renal Failure, n Yes 211 (8.8) 56 (8.0) 155 (9.1) 2,183 (91.2) 644 (92.0) 1,539 (90.9) 0.384 COPD, n Yes 236 (9.9) 62 (8.9) 174 (10.3) 2,158 (90.1) 638 (91.1) 1,520 (89.7) 0.293 SD (Standard Deviation); COPD (Chronic Obstructive Pulmonary Disease) 노인환자통증관리가이드라인에서는 acetaminophen을 1 차적으로사용하고, 통증완화실패시마약성진통제를추가하는것을권고하고있다. 13) 하지만본연구의결과, 비마약성

노인입원환자의비암성통증에대한약물처방현황 / 149 Table 7. Results of logistic regression on factors associated with any analgesic prescriptions. OR (95% CI) Fracture Yes 2.394 (1.766-3.244) OR (Odds Ratio); CI (Confidence Interval) p-value < 0.001 진통제의처방이없이마약성진통제만을처방받은환자가 85명 (3.6%) 이었다. 호주의한연구에서는노인요양병원에거주하는노인들중정기적으로마약성진통제만을복용하는경우는 2.1% 로본연구결과에비하여그비율이낮았다. 14) 진통제처방순위는마약성진통제중에서는 pethidine 이 45.7% 로가장많이처방되었고, fentanyl이 33.2% 로두번째이었다. 마약성진통제중에서 pethidine과 fentanyl과같이작용이강하고짧은시간동안작용하는약물들이중등도이상의급성통증과마취, 수술관련통증관리에많이사용되는것으로보인다. 특히 fentanyl의경우, 변비, 오심, 졸림등과같은마약성진통제와관련한부작용발생이적고다양한제형이있어처방빈도가높은것으로사료된다. 12) 비마약성진통제의처방순위는 acetaminophen이 44.1% 로가장처방건수가많았으며, diclofenac이 18.6% 로두번째로많았다. Acetaminophen은간부전과같은간질환을가지고있지않은경우에는통증관리에있어안전성과효과가입증되어있으므로 1차로선택을하기때문에가장빈번하게처방되는것으로사료된다. 10,14) 마약성진통제를처방받은환자군과미처방군을대상으로 multivariate logistic regression analysis를시행한결과, 골절이있는경우에골절이없는경우에비하여마약성진통제를처방받을가능성이 2.766 배이었다. 골절환자에있어서는비마약성진통제중 acetaminophen보다는비스테로이드성소염진통제를더많이사용하는데, 비스테로이드성소염진통제는노인환자에게있어위장관독성, 심장독성, 신장독성등의부작용발생의위험이증가하기때문에마약성진통제를사용하는것이권고된다. 14,15) 호주의연구에서도골절을동반질환으로가진환자의경우정기적으로마약성진통제를사용할가능성이 1.54 배이었다 (95% CI = 1.32-1.80). 14) 치매를동반질환으로가진환자의경우통증을느낄때의사소통이원활하지않아서적절한진통제를처방받지못하는경향이있다. 16) 하지만본연구에서는 logistic regression analysis 결과치매가진통제처방에통계적으로유의한영향을미치지는않았다. 치매환자의통증관리를위해서는 acetaminophen이가장많이처방되고있으며, 비스테로이드성소염진통제와마약성진통제도사용한다. 17) 마약성진통제는진정작용이있고, 인지장애를악화시킬수있어치매환자에게사용할경우에는더욱주의를기울여야한다. 18) 뇌졸중또는뇌경색이있는환자 의경우마약성진통제를처방받을가능성이 0.636 배이었다. 이는 acetaminophen이 1차선택약으로사용되고, 마약성진통제를사용할경우뇌졸중환자에게부정적영향을미칠수있기때문인것으로사료된다. 19,20) 본연구는다음과같은한계점이있다. 연구에포함된환자수가상대적으로적었다. 그리고통증의원인과진통제사용효과 ( 만족도 ) 에대한조사가이루어지지않았고, 진통제선택에영향을줄가능성이있는환자가복용하고있는병용약물에대한정보가없다. 그리고한대학병원에서의진통제사용양상에대한연구이므로본연구결과가국내종합병원전체에대한대표성을가지지는않는다. 그러나, 국내노인환자들의통증관리에대한연구가매우제한적인현재상황에서본연구는통증에대한약물처방현황을분석하고, 관련인자들을밝혔다는점에서의의가있다. 통증관리는보건의료전문인에게환자본인의증상을자가보고를하는것이중요한데, 노인의경우뇌졸중, 치매, 파킨슨병등의질환으로인하여통증을제대로호소하지못하는경향이많다. 10) 그리고노인의경우대부분다른기저질환을가지고있으며, 이로인하여다양한약물을복용하고있다. 17) 노인은신장혈류량이줄고신사구체여과속도가줄어약물의배설이감소하고, 간부피와간혈류의감소로초회통과효과도감소한다. 21) 그러나비암성통증관리에관하여, 마약성진통제를포함한진통제사용전반에관한국내의지침은없는실정이다. 보건의료전문인들은노인환자들의개별상황에따라진통제선택과용량조절에있어서신중을기해야하고, 투여후모니터링을하여최소한의부작용으로최대한의진통관리를하여환자의삶의질을높이도록노력해야한다. 참고문헌 1. Wang H, Dwyer-Lindgren L, Lofgren KT, et al. Age-specific and sexspecific mortality in 187 countries, 1970-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2013;380(9859): 2071-94. 2. Gibson SJ. IASP global year against pain in older persons: highlighting the current status and future perspectives in geriatric pain. Expert Rev Neurother 2007;7(6):627-35. 3. Maxwell CJ, Dalby DM, Slater M, et al. The prevalence and management of current daily pain among older home care clients. Pain 2008; 138(1):208-16. 4. Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 2006;10(4):287-333. 5. ble M, Treadwell JR, Tregear SJ, et al. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev 2010; 1(1):CD006605. 6. Lapane KL, Quilliam BJ, Chow W, et al. Pharmacologic management of non-cancer pain among nursing home residents. J Pain Symptom Manage 2013;45(1):33-42.

150 / Korean J Clin Pharm, Vol. 25,. 3, 2015 7. Won AB, Lapane KL, Vallow S, et al. Persistent nonmalignant pain and analgesic prescribing patterns in elderly nursing home residents. J Am Geriatr Soc 2004;52(6):867-74. 8. Siddall PJ, Cousins MJ. Persistent pain as a disease entity: implications for clinical management. Anesth Analg 2004;99(2):510-20. 9. Ferrell B, Argoff CE, Epplin J, et al. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc 2009;57(8):1331-46. 10. King SA. Chronic Pain Management in the Elderly: An Update on Safe, Effective Options. Consultant 2012;52(5):326-31. 11. Coluzzi F, Pappagallo M. Opioid therapy for chronic noncancer pain: practice guidelines for initiation and maintenance of therapy. Minerva anestesiol 2004;71(7-8):425-33. 12. Abdulla A, Adams N, Bone M, et al. Guidance on the management of pain in older people. Age and ageing 2013;42(Suppl 1):i1-57. 13. Tracy B, Morrison RS. Pain management in older adults. Clin Ther 2013;35(11):1659-68. 14. Veal FC, Bereznicki LR, Thompson AJ, et al. Pharmacological management of pain in Australian aged care facilities. Age and ageing 2014;43(6):851-6. 15. Gianni W, Ceci M, Bustacchini S, et al. Opioids for the treatment of chronic non-cancer pain in older people. Drugs Aging 2009;26(1):63-73. 16. Achterberg WP, Pieper MJ, van Dalen-Kok AH, et al. Pain management in patients with dementia. Clin Interv Aging 2013;8:1471-82. 17. Scherder E, Herr K, Pickering G, et al. Pain in dementia. Pain 2009; 145(3):276-8. 18. Pergolizzi J, Böger RH, Budd K, et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract 2008; 8(4):287-313. 19. Zorowitz RD, Smout RJ, Gassaway JA, et al. Usage of pain medications during stroke rehabilitation: the Post-Stroke Rehabilitation Outcomes Project (PSROP). Top Stroke Rehabil 2005;12(4):37-49. 20. Lee CW, Muo CH, Liang JA, Sung FC, Kao CH. Association of intensive morphine treatment and increased stroke incidence in prostate cancer patients: a population-based nested case-control study. Jpn J Clin Oncol 2013;43(8):776-81. 21. Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 2004;57(1):6-14.