Comparison of Published Explicit Criteria for Potentially Inappropriate Medications in Older Adults

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1 DC\/ICU/ A DTir^l C Diugs Aging 010; (1); KCVICW MKII^LC 11O.9X/10/ /S49.95/0 010 Adis Dota Information BV. All tights resolved. Comparison of Published Explicit Criteria for Potentially Inappropriate Medications in Older Adults Chirn-Bin Chang^'^ and Ding-Cheng Chan^ 1 Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan Contents Abstract Introduction Potentially Inappropriate Medications (PIMs) Measures to Identify PiMs Methods for Deveioping Expiicif Criteria for PiMs 948. Aims and Metiiodology Published Explicit Criteria and Their Outcome Studies Beers Criteria McLeod Criteria Rancourt Criteria Laroche Criteria Screening Tooi of Oider Persons' Potentiaiiy Inappropriate Prescriptions Winit-Watjana Criteria Norwegian General Practice Criteria Studies of Prevaience of PiMs and Related Heaith Outcomes Prevaience Studies Outcome Studies Simiiarities and Differences in PIMs Listed in the Seven Explicit Criteria Simiiarities in PiMs Among the Seven Criteria Differences in PIMs Among the Seven Criteria Optimai Explicit Criteria for PiMs Improving Application of PiMs Criteria in Daiiy Practice Conciusions 955 AbStrOCt Several sets of explicit criteria for potentially inappropriate medications (PIMs) have been developed by expert consensus. The purpose of this review is to summarize and compare existing criteria to enable more informed choices about their use. After a systematic literature search was conducted, seven examples of criteria published between 1991 and 009 were included in the review and their individual characteristics are presented. Common medications listed in the majority of these criteria are also summarized. PIMs listed regardless of co-morbidities in all seven criteria sets were long-acting benzodiazepines and tricyclic antidepressants. PIMs regardless of co-morbidities

2 948 Chang & Chan were most similar among the Beers, Rancourt and Winit-Watjana criteria. Several drug-disease interactions such as benzodiazepines and falls were cited in most criteria. With respect tp drug-drug interactions, most criteria agreed that concomitant use of warfarin and NSAIDs should be avoided. The prevalence of PIMs varied with patient population, availability of medications in local markets, the specialties ofthe prescribing physicians and the assessment instruments used. The associations between PIMs use and health outcomes were largely inconclusive because of limited data. Further research is necessary to validate these published criteria in terms of reducing the incidence of adverse drug reactions and improving health outcomes among older adults. Incorporation of these criteria into computer-assisted order entry systems would increase their utilization in daily practice. 1. Introduction 1.1 Potentially Inappropriate ivledications (PIMs) The term 'potentially inappropriate medications' (PIMs) or 'potentially inappropriate prescriptions' is used to describe "medications [that] have no clear evidence-based indication, carry a substantially higher risk of adverse side-effects or [are] not costeffective."!'! Efforts have been made to reduce the use of PIMs as a strategy for minimizing adverse drug reactions (ADRs) among older adults.pl Several previous studies have suggested that use of PIMs significantly increases the incidence of ADRs among older adults.^^"^^ However, only a small proportion of ADRs have been found to be caused by PIMs,t^'''l and it is not known whether reducing PIMs can improve patient outcomes. 1. Measures to identify PIMs Implicit (judgement-based) and explicit (criteriabased) measures have been developed to assess the appropriateness of prescriptions. Implicit criteria such as the Medication Appropriateness Indext^' are used to assess each medication prescribed for a patient after considering its indication, effectiveness, dosage, correct direction, cost and other clinical information required to determine its appropriateness. Those reviewing the patient's medications (often clinical pharmacists) need to have a comprehensive knowledge of medications to confidently determine their appropriateness. Explicit criteria are usually established by expert consensus to create lists of medications to be avoided among older adults, either in general or in the presence of specific co-morbidities. Explicit criteria are often easier to implement in routine clinical practice because only limited numbers of medications and clinical conditions are specified. Physicians who are familiar with explicit criteria may prescribe fewer PIMs when treating elderly patients.f^' Medication reviewers may also employ these criteria to quickly identify PIMs and recommend adjustments to the medication prescribersj'"' Explicit criteria are often used in studies of prevalence and health outcomes associated with 1.3 Methods for Developing Explicit Criteria for PIMs All explicit PIM criteria have been developed using a modified method. This method is used to deal with controversial issues through expert consensus reached after administration of questionnaires with controlled feedbackj'^' The research group constructs questions about the appropriateness of specific medication use on the basis of a review ofthe literature. Selected experts are then asked to rate their agreement with statements about candidate PIMs using a fivepoint Likert scale. Statements with agreement above certain cut-points are circulated again for second or third ratings. Finally, PIMs that generate a high degree of agreement about their inappropriateness amongst the experts are listed. 010 Adis Data Information BV. All rights reserved. Drugs Aging 010; (1)

3 Comparisons of Published PIM Ctiteria 949. Aims and Methodology The first aim of this review is to provide summaries and comparisons of published explicit criteria of PIMs in different countries. Application of these criteria in various clinical settings as well as their associations with ADRs, healthcare resource utilization and other outcomes are also reviewed. The most widely cited explicit criteria for PIMs are the Beers criteria, which were most recently revised in 003.f'^' However, approximately half of the medications listed in these criteria are unavailable in Europet'''] or Asia,''^ and the arrangement of medications/medication classes in the Beers criteria is not well ordered. Several drugs in the Beers criteria, e.g. amiodarone, doxazosin and naproxen, also have debatable appropriateness in the minds of different expert groups.''"' As a result, other criteria for identifying PIMs have been developed by different countries. We searched the English language literature in PubMed from January 1991 (the year when the first version ofthe Beers criteria''^' was published) to December 009 using the following terms: 'elderly', 'prescriptions', 'prescribing', 'medications', 'drugs', 'explicit criteria' and 'potentially inappropriate'. Thirteen sets of explicit criteria for PIMs were found, including the Beers criteria (1991, ] j^nd 003ti31 editions), the Zhan criteria,''^1 the Health Plan Employer Data and Information Set (HEDIS) criteria,!'^! the Assessing Care of Vulnerable Elders (ACOVE) quality indicators,'^"' the McLeod criteria,'^'' the Improving Prescribing in the Elderly Tool (IPFT),'^^' the Rancourt criteria,'^^' the Laroche criteria,'^'*' the Screening Tool of Older Person's potentially inappropriate Prescriptions (STOPP),^^) the Winit- Watjana criteria''^' and the Norwegian General Practice (NORGEP) criteria.p^l We compared the similarities and differences among medications listed in different criteria. We also summarized PIM prevalence and outcomes in studies applying these criteria. However, after reviewing the text of all of the criteria, we found that the Zhan and HEDIS criteria were reclassifications ofthe 199 and 003 Beers criteria, respectively. The PIMs in the ACOVE quality indicators were also derived from the 003 Beers criteria. Similarly, the IPFT was a simplified version of the McLeod criteria. To avoid duplications, these four sets of criteria were excluded from criteria comparisons. However, for completeness, a description of their use in published studies is still included in this review. For the three versions of the Beers criteria, only the 003 edition was included in our comparison tables. 3. Published Explicit Criteria and Their Outcome Studies Table I shows the basic characteristics of the explicit criteria for PIMs evaluated in this review. 3.1 Beers Criteria The original Beers criteria were designed to detect PIMs for elderly nursing home residents in J 991 [16] jjjg criteria were revised for application to community-dwelling older adults in 199.['^1 The third edition of the Beers criteria was published by Fick et al.''^' in 003 after the elimination of 15 outdated statements and the addition of 44 new statements. The revised criteria contained two categories of PIMs: (i) 48 medications/ medication classes to be avoided irrespective of diagnoses; and (ii) 0 diseases/conditions with corresponding medications/medication classes to be avoided in patients with these conditions. Among the 68 medications/medication classes identified as constituting PIMs, 5 were classified as being of high severity and 16 as low severity. 3. McLeod Criteria McLeod et al.'^'' published the Canadian consensus panel list of PIMs in 199. These PIMs were categorized as cardiovascular, psychotropic, NSAIDs/other analgesics and miscellaneous drugs. The 38 medications/medication classes included 16 drugs generally to be avoided, 11 drug-disease interactions and 11 drug-drug interactions. In addition, mean clinical significance ratings were given for each drug by the experts to a maximum of four points. Most PIMs scored greater than three points. These criteria also contained suggestions for alternative medications. Naugler et al.'^^l identified the most frequently encountered 14 of 010 Adis Data Information BV. Aii rights reserved. Drugs Aging 010: (1)

4 950 Chang & Chan Table I. Basic characteristics of the seven sets ot explicit criteria of potentiaily inappropriate medications evaluated Characteristics Year Country Authors Method Experts (n) rounds Applicable age group (y) Statements (n) Drug-disease interactions (n) Drug-drug interactions (n) Prescription dupiications (n) Suggestions for alternative drugs provided Prevalence (%) a community hospital long-term care Beers 003 US Fick 1 > No 18.3^ Prevalence range given for Beers criteria data. = not available; NORGEP = Nonvegian General Prescriptions criteria. McLeod 199 Canada McLeod 3 > Yes Rancourt 004 Canada Rancourt 4 > No 54. Laroche 00 France Laroche 15 > Yes STOPP 008 Ireland Gallagher Practice criteria; STOPP = Screening Tool of Older Person's potentially inappropriate 18 > No Winit-Watjana 008 Thailand Winit-Watjana et ai.''^' No NORGEP 009 Norway Rognstad 4 3 > No the 38 PIMs identified in these criteria and used these to develop the Improving Prescribing in the Elderly Tool (IPET). 3.3 Rancourt Criteria Developed by a geriatrics research team in Canada, the Rancourt criteria had four potentially inappropriate categories (total number of statements 111): (i) medications (n=4); (ii) duration (n=1); (iii) dosage (n = 0); and (iv) drug-drug interactions (n = 3).'^-'l One unique feature was that the generic name and Anatomical Therapeutic Chemical classification code for each medication available in Canada were listed. 3.4 Laroohe Criteria These criteria were published by Laroche et al.'^'*' in 00 for application to the population aged >5 years. The 34 statements were categorized into unfavourable benefit-risk ratio (n = 5), questionable efficacy (n=l), both unfavourable benefit-risk ratio and questionable efficacy (n = 6), and drug-drug interactions (n = ). Similar to the Rancourt criteria, all generic medications used in France were clearly listed and alternative drugs were suggested. 3.5 Screening Tool of Older Persons' Potentiaiiy Inappropriate Prescriptions This tool, which was designed by Gallagher et al.'51 in 008 for the population aged >65 years, had two parts. The STOPP was used to detect PIMs and the Screening Tool to Alert doctors to Right Treatment (START) was used to detect omissions in the prescribing of clearly indicated drugs. The 65 PIM statements in the STOPP were grouped into eight physiological system-based divisions. 3.6 Winit-Watjana Criteria The Winit-Watjana criteria published in 008 comprised the first Asian PIM list and were applied to older Thai adults.''^^ The three categories for the statements were (i) high-risk medications with potential adverse reactions (n = 33); (ii) high-risk medications with drug-disease interactions (n = 3); and (iii) high-risk medications 010 Adis Data Information BV. All rights reserved. Drugs Aging 010: (1)

5 Comparisons of Published PIM Criteria 951 with drug-drug interactions (n= 1). The authors preferred the term 'high-risk medications' to PIMs. They also regrouped these medications/medication classes as (i) drugs that should be avoided (n = 5); (ii) drugs that are rarely appropriate (n = ); (iii) drugs with some indications for older patients (n= 11); and (iv) unclassified drugs (n=54). Since 0% (54/) of the statements involved unclassified medications/medication classes, the usefulness of the latter grouping system was limited. 3. Norwegian Gênerai Practice Criteria Based on the consensus of experts in Norway, the NORGEP criteria were established in 009 by Rognstad et al.'^*' for patients aged >0 years. Thirty-six medications/medication classes were categorized into 1 single drugs and 15 drug combinations that were considered potentially inappropriate. There were no statements for drugdisease interactions or suggestions of alternative medications. 3.8 Studies of Prevaience of PiMs and Related Heaith Oufcomes We also reviewed the articles that applied these criteria to determine the prevalence of PIMs in different clinical settings and to identify the associations between PIMs and various health outcomes. Most of the studies used the Beers criteria and its modified edition, such as the HEDIS measure; few were based on the McLeod, Rancourt or STOPP criteria. No studies published in English as at December 009 had applied the three relatively new criteria developed in France, Norway and Thailand Prevalence Studies The prevalence of PIMs using the 003 version of Beers criteria ranged from 18% to 4% in the community,[''*'''-3' from 18% to 35% in longterm care facilities'^^'^'*' and from 14% to 44% in hospitals.t^'^^'-'^' Most of the studies were conducted in the US and the UK; other settings included Croatia, Czech Republic, Denmark, Finland, Iceland, Italy, Japan, the Netherlands, Norway, Switzerland and Taiwan. The prevalence of PIMs using the HEDIS criteria was 0% for older adults cared for in the US Veterans Affairs health system.''^' A computerized program applying the McLeod criteria found that 15% of 356 long-term care residents had PIMs in Canada.'''"' A combined instrument with 4 medications/medication classes from either the Beers or McLeod criteria found that 40% of hospitalized elderly patients in the US had PIMs.'""' The prevalence of PIMs using the IPFT (simplified McLeod criteria) was 13% in the hospital setting in Canada'^^1 and 10% in the community in Ireland, compared with 13% when the Beers criteria were used.'"*^' According to the Rancourt criteria, over half (55%) of residents in long-term care units used PIMs in Canada.'^^' The STOPP criteria identified more PIMs than the Beers criteria in both the community (1% vs 18%)'^ ' and the hospital setting (35% vs 5%) in Ireland.'^^' The prevalence of PIMs varies with geography, the characteristics of the prescribers, the co-morbidities of the study populations and the criteria that are used to assess PIMs.'''*' In an international survey conducted in eight European countries, Fialova et al.'''*' found that the prevalence of PIMs varied (from 41% in Western Europe to 6-% in Eastern Europe). These investigators concluded that the different prevalences reflected inequalities in drug policies, care provisions, overall health conditions and socioeconomic backgrounds. Physicians who prescribed PIMs more frequently were more likely to be older or male.'^^-'*^' In contrast, older adults who received geriatric care were less likely to have PIMs than those who received usual care.''*'*-''^' When the Beers criteria were used, most studies applied the criteria only in terms of medications that were potentially inappropriate irrespective of co-morbidities, omitting those that were considered potentially inappropriate in patients with certain diseases/conditions because of a lack of information on co-morbidities. Studies applying only parts of the Beers criteria in this way often reported a lower prevalence of PIMs than studies that applied the full criteria. Several statements did not specify the individual drug names included in each medication class. Studies might have varied in defining drugs within medication 010 Adis Data Information BV. All rigtits reserved. Drugs Aging 010: (1)

6 95 Chang & Chan classes, which would have increased variations in prevalence estimates of PIMs.t'*^^ 3.8. Outcome Studies ADRs may increase the chances of functional decline, mortality and increased healthcare costs in older populations.!'*^'''^ Since 80% of ADRs are considered preventable,i'*^' PIM-related ADRs would also be largely preventable. As at December 009, all published outcome studies had used only the Beers criteria. One study showed a significantly increased risk of ADRs (odds ratio.3) in 186 hospitalized older patients.f^' However, other studies found no such association.i^'^^' While it might be thought that Beers criteria PIMs might be responsible for an increased risk of ADRs, in fact they were the cause of only a relatively small percentage of ADRs (6%t3'l and 9%[''^1) in hospitalized elders. Similarly, only 4%[^ 1 of ADRs leading to emergency department visits were caused by Beers criteria PIMs. It is not known whether a decreased use of PIMs would actually reduce the prevalence of ADRs; further studies are needed. Regarding other health outcomes, only limited studies have reported that use of PIMs listed in the Beers criteria increased healthcare resource utilizationp^'^'i and nursing home admissions.t^^' No study demonstrating that reducing PIM use might improve these outcomes was found. 4. Similarities and Differences in PiiVIs Listed in the Seven Explicit Criteria 4.1 Similarities in PIMs Among the Seven Criteria We found few similarities in PIMs listed in the seven explicit criteria. However, the similarities in the category of PIMs irrespective of co-morbidities were largest among the Beers, Rancourt and Winit-Watjana criteria. Table II summarizes the medications/medication classes included in at least four of the seven criteria irrespective of comorbidities. Only long-acting benzodiazepines (chlordiazepoxide, diazepam) and tricyclic antidepressants (amitriptyline, doxepin) were considered inappropriate by all seven criteria. Long-acting benzodiazepines are associated with increased risk of confusion, sedation, falls and hip fractures.t^^'^^] However, the half-life of the benzodiazepine was not consistently associated with the risk of falls and hip fracture.^^^^ Even shortacting benzodiazepines were strongly associated with fall-related injuries.'^^' Therefore, clinicians should regularly evaluate the indication, dose and duration of treatment when prescribing any benzodiazepine in older patients. Tricyclic antidepressants with strong anticholinergic effects introduce risks of impaired cognitive function, falls, constipation, urinary retention and cardiotoxicity.'^'*'^^ Nowadays, tricyclic antidepressants have been largely replaced by selective serotonin reuptake inhibitors (SSRIs) because of reduced adverse effects. Table III summarizes medications/medication classes that could be involved in drug-disease interactions that were listed in at least four published criteria. Among them, medications with anticholinergic effects, NSAIDs, a-adrenoceptor antagonists and benzodiazepines were often cited for older adults with specific medical problems such as falls, peptic ulcers, urinary incontinence or cognitive impairment. In regard to drug-drug interactions, only concomitant use of NSAIDs and warfarin was mentioned in all but the Laroche criteria. Concomitant use of these two drugs increased the risk for CNS and gastrointestinal bleeding by at least - and 13-fold, respectively.t^^'^'^l The PIMs listed in table II and table III were the most uniformly agreed upon statements among experts from Europe, North America and Asia. 4. Difterences in PIMs Among the Seven Criteria The differences in PIMs among the seven criteria mainly reflected differences in medication availability and prescribing patterns in the different countries. However, there were also different opinions on the inappropriateness of certain medications expressed in criteria published in Europe and North America, particularly with respect to atniodarone, doxazosin and fluoxetine.t'-''^'*' Amiodarone was considered inappropriate in the Beers criteria because it was associated with risk of QT interval prolongation and torsades de pointes, and with lack of efficacy in older patients.i'^l In 0)0 Adis Data Information BV. All rights reserved. Drugs Aging 010: (1)

7 Comparisons of Published PIM Criteria 953 Table II. Medications included in at least four ot the seven criteria ot potentially inappropriate medications Medication class/medication Analgesics Indometacin Phenylbutazone Muscle relaxants Methocarbamol Carisoprodol Antispasmodics Hyoscyatnine Hypnotics and sedatives Long-acting benzodiazepines Barbiturates Antidepressants Tricyclic antidepressants First-generation antihistamines Chlorphenamine (chlorpheniramine) Diphenhydramine Hydroxyzine Promethazine Dexchlorpheniramine Cardiovascular drugs Dipyridamole Digoxin Methyldopa Reserpine Oral antlhyperglycaemic drugs Chlorpropamide Antipsychotics Chlorpromazine Miscellaneous Cimetidine Theophylline Beers McLeod. Rancourt Laroche STOPP Winit-Watjana NORGEP NORGEP = Norwegian General Practice criteria; STOPP = Screening Tool of Older Person's potentially inappropriate Prescriptions criteria. contrast, amiodarone was not listed in criteria published in Europe because it was considered effective and its adverse effect profile to be similar to other antiarrhythmics.p'*' Doxazosin was considered a PIM in the Beers criteria because of a high risk for postural hypotension. However, other experts felt that because doxazosin had dual effects in controlling blood pressure and bladder outflow obstruction, the overall benefit-risk ratio profile was favourable when older adults presented with these two conditions. Use of fluoxetine was not considered inappropriate by French experts because its adverse effect profile was similar to that of other SSRIs.^"*' The STOPP criteria listed war- farin as an inappropriate medication when used for >6 months for first, uncomplicated deep venous thrombosis or pulmonary embolus.^^^l This state- ment was not included in the other six criteria, ^ 3 ^^^^-^^^ g^p ^ ^ Criteria for PIMs O'Mahony and Gallagher^'' proposed the fol- lowing six principles for selecting optimal explicit criteria: (i) organization based on physiological 010 Adis Data Information BV. Aii rights reserved. Drugs Aging 010; (1)

8 954 Chang & Chan Table III. Drug-disease interactions mentioned in at least tour of the seven criteria of potentiaily inappropriate medications Medication class/medication Antichoiinergics a-adrenoceptor antagonists NSAIDs, including aspirin (acetylsalicylic acid) Benzodiazepines ß-Adrenoceptor antagonists Beers Urinary retention, cognitive impairment, chronic constipation Urinary incontinence Blood clotting disorder. peptic ulcer disease Depression, urinary incontinence. syncope or falls, COPD COPD McLeod Cognitive impairment Peptic ulcer disease. chronic kidney disease, heart faiiure. hypertension Fails, dementia COPD Rancourt Laroche Urinary retention. dementia. glaucoma, chronic constipation Urinary incontinence Faiis, dementia STOPP Urinary retention. dementia. glaucoma, chronic constipation Urinary incontinence Peptic ulcer disease, bleeding disorder. hypertension, heart failure, chronic kidney disease Falis COPD Winit-Watjana Urinary retention. cognitive impairment. constipation urinary incontinence Peptic ulcer disease, blood clotting disorder. hypertension, heart failure, chronic kidney disease Falls, COPD, sleep apnoea syndrome COPD NORGEP COPD = chronic obstructive pulmonary disease; = not availabie; NORGEP = Nonwegian General Practice criteria; STOPP = Screening Tool of Older Person's potentiaiiy inappropriate Prescriptions criteria. Falls systems and rapid applicability in daily practice; (ii) inclusion of the more common errors of commission and omission in prescribing for older adults; (iii) generalizability to the global community of physicians and pharmacists; (iv) ease of interface with computer records of co-morbidities of patients and lists of drugs; (v) ability to reduce the prevalence of PIMs in older adults in different settings; and (vi) ability to reduce the incidence and negative impact of ADRs.''' It is evident that none of the seven criteria met all these principles because no studies showed that decreased use of PIMs improved outcomes. Table IV summarizes the performance of the seven criteria relative to these six principles. In our opinion, the STOPP, Rancourt and Laroche criteria came closest to fully meeting the optimal explicit criteria (table IV). Since we Table IV. Evaluation of the seven criteria against the principles of optimal explicit criteria for potentially inappropriate medications (PIMs) proposed by O'Mahony and Gaiiagherf^i Principle Beers McLeod Rancourt Laroche STOPP Winit-Watjana NORGEP t. Organization based on physiological systems - - +/- +/_ + _ and rapid applicability in daily practice. Inclusion of common prescribing errors +/- +/- +/- +/- +/- +/- +/- (commission and omission) 3. Generalizability to the global community of +/- +/- +/- +/- +/- +/- +/_ physicians and pharmacists 4. Ease of interface with computer records of - - +/- + +/- +/_ + patients and drug lists 5. Ability to reduce the prevalence of PIMs NS + NS NS 6. Ability to reduce the incidence and negative NS NS NS NS NS NS NS impact of ADRs ADRs = adverse drug reactions; NORGEP = Nonwegian General Practice criteria; NS = no studies; STOPP = Screening Tool of Oider Person's potentially inappropriate Prescriptions criteria; + indicates fully met; +/- indicates partially met; - indicates not met. 010 Adis Data Information BV. Aii rights reserved. Drugs Aging 010: (1)

9 Comparisons of Published PIM Criteria 955 included only English-language articles, we would have not identified any prevalence or outcome studies that applied the Laroche, Winit-Watjana or NORGEP criteria in articles published in the non- English literature. As all criteria were developed through expert consensus, the level of evidence may not be optimal. Future studies of drugs should include more older adults in the study population to further establish the adverse reaction profiles in this age group. Newly developed PIM criteria could then be supported by higher levels of evidence. 5. Improving Application of PIMs Criteria in Daily Practice Several strategies could increase the application of PIMs criteria in routine practice. The first would be to include PIMs as quality indicators of healthcare, as in the HEDIS measure. Healthcare organizations would then need to make an effort to reduce their PIM rates in order to comply with regulations. Second, many prescription-related problems can be prevented at the stage of ordering medications. Various computerized prescribing systems have been shown to be beneficial in terms of improving prescription quality, as demonstrated in a systematic review.'^*' Incorporation of these criteria into a computer-assisted ordering system could also decrease prescriptions of PIMs and their consequent negative impacts. 6. Conclusions Few similarities were found among the published explicit criteria for PIMs for older adults. However, most experts agreed that use of longacting benzodiazepines, tricyclic antidepressants, and concomitant NSAIDs and warfarin should be avoided. Since all criteria were developed by expert consensus, further validation studies are needed to determine the ability of these criteria to reduce the incidence of ADRs and improve health outcomes. If validated explicit criteria could be established and integrated into computerized medication ordering systems, their usage could be widely disseminated and PIMs could be efficiently and effectively avoided in older adults. Acknowledgements No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review. The authors thank Dr Ichun Hsieh for reviewing and editing the article. References 1. O'Mahony D, Gallagher PF. Inappropriate prescribing in the older population; need for new criteria. Age Ageing 008 Mar; 3 (); Laroche ML, Charmes JP, Bouthier F, et al Inappropriate medications in the elderly. Clin Pharmacol Ther 009 Jan; 85 (1); Lindley CM, Tully MP, Paramsothy V, et al. Inappropriate medication is a major cause of adverse drug reactions in elderly patients. Age Ageing 199 Jul; 1 (4): Chang CM, Liu PY, Yang YH, et al. Use of the Beers criteria to predict adverse drug reactions among first-visit elderly outpatients. Pharmacotherapy 005 Jun; 5 (6); Passarelli MCG, Jacob W, Figueras A. Adverse drug reactions in an elderly hospitalised population; inappropriate prescription is a leading cause. Drugs Aging 005; (9); 6-6. Onder G, Landi F, Liperoti R, et al. Impact of inappropriate drug use among hospitalized older adults. Eur J Clin Pharmacol 005 Jul; 61 (5-6); Laroche ML, Charmes JP, Nouaille Y, et al. Is inappropriate medication use a major cause of adverse drug reactions in the elderly? Br J Clin Pharmacol 00 Feb; 63 (); Hanlon JT, Schmader KE, Samsa GP, et al. A method for assessing drug therapy appropriateness. J Clin Epidemiol 199Oct;45(10); Kaur S, Mitchell G, Vitatte L, et al. Interventions that can reduce inappropriate prescribing in the elderly; a systematic review. Drugs Aging 009; 6 (1): Spinewine A, Schmader KE, Barber N, et al. Appropriate prescribing in elderly people: how well can it be measured and optimised? Lancet 00 Jul 14; 30 (958); Jano E, Aparasu RR. Healthcare outcomes associated with Beers' criteria; a systematic review. Ann Pharmacother 00 Mar; 41 (3); Day J, Bobeva M. A generic toolkit for the successful management of studies. EJBRM 005; 3 (); Fiek DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Areh Intern Med 003 Dec 8-; 163 (): Fialova D, Topinkova E, Gambassi G, et al. Potentially inappropriate medication use among elderly home care patients in Europe. JAMA 005 Mar 16; 93 (11); Winit-Watjana W, Sakulrat P, Kespichayawattana J. Criteria for high-risk medication use in Thai older patients. Arch Gerontol Geriatr 008 Jul-Aug; 4 (1); Beers MH, Ouslander JG, Rollingher I, et al. Explicit criteria for determining inappropriate medication use in nursing home residents. UCLA Division of Geriatric Medicine. Arch Intern Med 1991 Sep; 151 (9); Adis Dota Information BV. All rights reserved. Drugs Aging 010; (1)

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11 Comparisons of Published PIM Criteria Cresswell KM, Fernando B, McKinstry B, et al. Adverse drug events in the elderiy. Br Med Bull 00; 83: Page nd RL, Ruscin JM. The risk of adverse drug events and hospital-related morbidity and mortality among older adults with potentially inappropriate medication use. Am J Geriatr Pharmacother 006 Dec; 4 (4): Budnitz DS, Shehab N, Kegler SR, et al. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med 00 Dec 4; 14 (11): Bonk ME, Krown H, Matuszewski K, et al. Potentially inappropriate medications in hospitalized senior patients. Am J Health Syst Pharm 006 Jun 15; 63 (1): Cumming RG, Le Couteur DG. Benzodiazepines and risk of hip fractures in older people: a review ofthe evidence. CNS Drugs 003; 1 (11): Pimlott NJG, Hux JE, Wilson LM, et al. Educating physicians to reduce benzodiazepine use by elderiy patients: a randomized controlled trial. CMAJ 003 Apr 1; 168 (): Beresford TP, Feinsilver DL, Hall RCW. Adverse reactions to a benzodiazepine-tricyclic anti-depressant compound. J Clin Psychopharmacol 1981; 1 (6): Kamath M, Finkel SI, Moran MB. A retrospective chart review of antidepressant use, effectiveness, and adverse effects in adults age 0 and older. Am J Geriatr Psychiatry 1996; 4 (): Shorr RI, Ray WA, Daugherty JR, et al. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 1993 Jul 6; 153(14): Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy; recent data and ideas. Stroke 005 Jul; 36 (): Pearson SA, Moxey A, Robertson J, et al. Do computerised clinical decision support systems for prescribing change practice? A systematic review ofthe literature ( ). BMC Health Serv Res 009; 9: 154 Correspondence: Dr Ding-Cheng Chan, Department of Geriatrics and Gerontology, National Taiwan University Hospital, 100 No 1, Chang-De Street, Taipei, Taiwan. doctord66@yahoo.com 010 Adis Data Information BV. Ali rights reserved. Drugs Aging 010. (1)

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