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Meta-Analysis
. 2018 Sep 3;9(9):CD008165.
doi: 10.1002/14651858.CD008165.pub4.

Interventions to improve the appropriate use of polypharmacy for older people

Audrey Rankin  1 , Cathal A Cadogan, Susan M Patterson, Ngaire Kerse, Chris R Cardwell, Marie C Bradley, Cristin Ryan, Carmel Hughes
Affiliations
Meta-Analysis

Interventions to improve the appropriate use of polypharmacy for older people

Audrey Rankin et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing. This is the second update of this Cochrane Review.

Objectives: To determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people.

Search methods: We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers up until 7 February 2018, together with handsearching of reference lists to identify additional studies.

Selection criteria: We included randomised trials, non-randomised trials, controlled before-after studies, and interrupted time series. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people aged 65 years and older, prescribed polypharmacy (four or more medicines), which used a validated tool to assess prescribing appropriateness. These tools can be classified as either implicit tools (judgement-based/based on expert professional judgement) or explicit tools (criterion-based, comprising lists of drugs to be avoided in older people).

Data collection and analysis: Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. We pooled study-specific estimates, and used a random-effects model to yield summary estimates of effect and 95% confidence intervals (CIs). We assessed the overall certainty of evidence for each outcome using the GRADE approach.

Main results: We identified 32 studies, 20 from this update. Included studies consisted of 18 randomised trials, 10 cluster randomised trials (one of which was a stepped-wedge design), two non-randomised trials and two controlled before-after studies. One intervention consisted of computerised decision support (CDS); and 31 were complex, multi-faceted pharmaceutical-care based approaches (i.e. the responsible provision of medicines to improve patient's outcomes), one of which incorporated a CDS component as part of their multi-faceted intervention. Interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals such as general physicians, pharmacists and geriatricians, and all were conducted in high-income countries. Assessments using the Cochrane 'Risk of bias' tool, found that there was a high and/or unclear risk of bias across a number of domains. Based on the GRADE approach, the overall certainty of evidence for each pooled outcome ranged from low to very low.It is uncertain whether pharmaceutical care improves medication appropriateness (as measured by an implicit tool), mean difference (MD) -4.76, 95% CI -9.20 to -0.33; 5 studies, N = 517; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the number of potentially inappropriate medications (PIMs), (standardised mean difference (SMD) -0.22, 95% CI -0.38 to -0.05; 7 studies; N = 1832; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PIMs, (risk ratio (RR) 0.79, 95% CI 0.61 to 1.02; 11 studies; N = 3079; very low-certainty evidence). Pharmaceutical care may slightly reduce the number of potential prescribing omissions (PPOs) (SMD -0.81, 95% CI -0.98 to -0.64; 2 studies; N = 569; low-certainty evidence), however it must be noted that this effect estimate is based on only two studies, which had serious limitations in terms of risk bias. Likewise, it is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PPOs (RR 0.40, 95% CI 0.18 to 0.85; 5 studies; N = 1310; very low-certainty evidence). Pharmaceutical care may make little or no difference in hospital admissions (data not pooled; 12 studies; N = 4052; low-certainty evidence). Pharmaceutical care may make little or no difference in quality of life (data not pooled; 12 studies; N = 3211; low-certainty evidence). Medication-related problems were reported in eight studies (N = 10,087) using different terms (e.g. adverse drug reactions, drug-drug interactions). No consistent intervention effect on medication-related problems was noted across studies.

Authors' conclusions: It is unclear whether interventions to improve appropriate polypharmacy, such as reviews of patients' prescriptions, resulted in clinically significant improvement; however, they may be slightly beneficial in terms of reducing potential prescribing omissions (PPOs); but this effect estimate is based on only two studies, which had serious limitations in terms of risk bias.

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Conflict of interest statement

AR: none known. CAC: none known. SP: none known. NK: none known. CRC: none known. MCB: none known. CR: none known. CH: none known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
4
4
Funnel plot of comparison: 1 Postintervention analysis, outcome: 1.1 Medication appropriateness (as measured by an implicit tool).
5
5
Funnel plot of comparison: 1 Postintervention analysis, outcome: 1.4 The number of potentially inappropriate medications.
6
6
Funnel plot of comparison: 1 Postintervention analysis, outcome: 1.5 The proportion of patients with one or more potentially inappropriate medications.
1.1
1.1. Analysis
Comparison 1 Postintervention analysis, Outcome 1 Medication appropriateness (as measured by an implicit tool).
1.2
1.2. Analysis
Comparison 1 Postintervention analysis, Outcome 2 Medication appropriateness (as measured by an implicit tool) (excl Crotty 2004a).
1.3
1.3. Analysis
Comparison 1 Postintervention analysis, Outcome 3 Medication appropriateness (as measured by an implicit tool) (excl Crotty 2004a and Spinewine 2007).
1.4
1.4. Analysis
Comparison 1 Postintervention analysis, Outcome 4 The number of potentially inappropriate medications.
1.5
1.5. Analysis
Comparison 1 Postintervention analysis, Outcome 5 The proportion of patients with one or more potentially inappropriate medications.
1.6
1.6. Analysis
Comparison 1 Postintervention analysis, Outcome 6 The proportion of patients with one or more potentially inappropriate medications (excl Spinewine 2007).
1.7
1.7. Analysis
Comparison 1 Postintervention analysis, Outcome 7 The proportion of patients with one or more potentially inappropriate medications (excl Spinewine 2007 and Gallagher 2011).
1.8
1.8. Analysis
Comparison 1 Postintervention analysis, Outcome 8 The number of potential prescribing omissions.
1.9
1.9. Analysis
Comparison 1 Postintervention analysis, Outcome 9 The proportion of patients with one or more potential prescribing omissions.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Meulendijk 2013 {published data only}
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Sellors 2003 {published data only}
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Simon 2005 {published data only}
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Simon 2006 {published data only}
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    1. Terrell KM, Perkins AJ, Dexter PR, Hui SL, Callahan CM, Miller DK. Computerized decision support to reduce potentially inappropriate prescribing to older emergency department patients: a randomized, controlled trial. Journal of the American Geriatrics Society 2009;57(8):1388‐94. - PubMed
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Thompson 2008 {published data only}
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Van Balen 2014 {published data only}
    1. Balen J, Damen‐Van Beek Z, Nelissen‐Vrancken M, Verduijn M, Woerkom M. Implementation and evaluation of the Dutch multidisciplinary guideline (MDR) polypharmacy in the elderly. International Journal of Clinical Pharmacy 2014;36:855.
Van Den Broucke 2014 {published data only}
    1. Broucke, Verhaeghe A, Debruyne PR, Verhelle K. Value of a clinical pharmacist in the oncology department and optimalisation of the applicability of geriatric tools assessing potential inappropriate medication use in geriatric patients (Drug Burden Index and de Beers criteria)]. French]. Journal de Pharmacie de Belgique 2014;94(1):28‐36. - PubMed
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    1. Vejar MV, Makic MB, Kotthoff‐Burrell E. Medication management for elderly patients in an academic primary care setting: a quality improvement project. Journal of the American Association of Nurse Practitioners 2015;27(2):72‐8. - PubMed
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Vetter 1992 {published data only}
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Weingart 2008 {published data only}
    1. Weingart SN, Hamrick HE, Tutkus S, Carbo A, Sands DZ, Tess A, et al. Medication safety messages for patients via the web portal: the MedCheck intervention. International Journal of Medical Informatics 2008;77(3):161‐8. - PubMed
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    1. Westberg SM, Swanoski MT, Renier CM, Gessert CE. Evaluation of the impact of comprehensive medication management services delivered posthospitalization on readmissions and emergency department visits. Journal of Managed Care & Specialty Pharmacy 2014;20(9):886‐93. - PMC - PubMed
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    1. Willeboordse F, Schellevis FG, Chau SH, Hugtenburg JG, Elders PJM. The effectiveness of optimised clinical medication reviews for geriatric patients: Opti‐Med a cluster randomised controlled trial. Family Practice 2017;34(4):437‐45. - PubMed
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    1. Williams ME, Pulliam CC, Hunter R, Johnson TM, Owens JE, Kincaid J, et al. The short‐term effect of interdisciplinary medication review on function and cost in ambulatory elderly people. Journal of the American Geriatrics Society 2004;52(1):93‐8. - PubMed
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    1. Taxis K, Scheper J, Koning H, Brouwer C, Twisk J, Meer H, et al. Discontinuing inappropriate medication in nursing home residents (DIM‐NHR study)‐a cluster randomized controlled trial. Pharmacoepidemiology and Drug Safety 2017;26:449‐50.
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    1. Wu JYF, Leung WYS, Chang S, Lee B, Zee B, Tong PCY, et al. Effectiveness of telephone counselling by a pharmacist in reducing mortality in patients receiving polypharmacy: randomised controlled trial. BMJ 2006;333(7567):522‐7. - PMC - PubMed
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    1. Wu S, Mirzaian E, Arouchanova D. The impact of a pharmacist intervention program for high‐risk medications on star ratings and identifying trends in patient resistance to high‐risk medication interventions in an independent community pharmacy practice. Journal of the American Pharmacists Association 2016;56(3):e25.
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    1. Zermansky AG, Alldred DP, Petty DR, Raynor DK, Freemantle N, Eastaugh J, et al. Clinical medication review by a pharmacist of elderly people living in care homes ‐ randomised controlled trial. Age and Ageing 2006;35(6):586‐91. - PubMed
Zuckerman 2005 {published data only}
    1. Zuckerman IH, Hernandez JJ, Gruber‐Baldini AL, Hebel JR, Stuart B, Zimmerman S, et al. Potentially inappropriate prescribing before and after nursing home admission among patients with and without dementia. American Journal Geriatric Pharmacotherapy 2005;3(4):246‐54. - PubMed

References to studies awaiting assessment

Cossette 2016 {published data only}
    1. Cossette B, Bergeron J, Ricard G, Ethier JF, Joly‐Mischlich T, Levine M, et al. Knowledge translation strategy to reduce the use of potentially inappropriate medications in hospitalized elderly adults. Journal of the American Geriatrics Society 2016;64(12):2487‐94. - PubMed
Cossette 2017 {published data only}
    1. Cossette B, Ethier J, Joly‐Mischlich T, Bergeron J, Ricard G, Brazeau S, et al. Reduction in potentially inappropriate medication use in elderly inpatients: a pragmatic randomized controlled trial. Journal of the American Geriatrics Society. 2017; Vol. 65:S109‐10. - PubMed
    1. Cossette B, Ethier JF, Joly‐Mischlich T, Bergeron J, Ricard G, Brazeau S, et al. Reduction in targeted potentially inappropriate medication use in elderly inpatients: a pragmatic randomized controlled trial. European Journal of Clinical Pharmacology 2017;73(10):1237‐45. - PubMed
Leguelinel‐Blache 2018 {published data only}
    1. Leguelinel‐Blache G, Castelli C, Roux‐Marson C, Bouvet S, Andrieu S, Cestac P, et al. Impact of collaborative pharmaceutical care on in‐patients' medication safety: Study protocol for a stepped wedge cluster randomized trial (MEDREV study). Trials 2018;19(1):19. - PMC - PubMed
Lenander 2017 {published data only}
    1. Lenander C, Bondesson A, Viberg N, Jakobsson U, Beckman A, Midlov P. Effects of an intervention (SAKLAK) on prescription of potentially inappropriate medication in elderly patients. Family Practice 2017;34(2):213‐8. - PubMed

References to ongoing studies

ACTRN12617000665336 {unpublished data only}
    1. ACTRN12617000665336. Impact of clinical pharmacist medication review on appropriate prescribing in elderly patients: A randomized, controlled trial. anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372670 (first received 30 March 2017).
Anrys 2016 {published data only}
    1. Anrys P, Goedele S, Foulon V, Spinewine A. The COME‐ON study: Collaborative approach to Optimise MEdication use for Older people in Nursing homes‐process evaluation protocol. International Journal of Clinical Pharmacy 2016a;38(4):1019.
    1. Anrys P, Strauven G, Boland B, Dalleur O, Declercq A, Degryse JM, et al. Collaborative approach to Optimise MEdication use for Older people in Nursing homes (COME‐ON): study protocol of a cluster controlled trial. Implementation Science 2016;11:35. - PMC - PubMed
Dauphinot 2017 {published data only}
    1. Dauphinot V, Jean‐Bart E, Krolak‐Salmon P, Mouchoux C. A multi‐center, randomized, controlled trial to assess the efficacy of optimization of drug prescribing in an elderly population, at 18 months of follow‐up, in the evolution of functional autonomy: the OPTIM study protocol. BMC Geriatrics 2017;17(1):195. - PMC - PubMed
Desborough 2011 {published data only}
    1. Desborough J, Houghton J, Wood J, Wright D, Holland R, Sach T, et al. Multi‐professional clinical medication reviews in care homes for the elderly: study protocol for a randomised controlled trial with cost effectiveness analysis. Trials 2011;12:218. - PMC - PubMed
DRKS00003610 {unpublished data only}
    1. DRKS00003610. Reduction of potentially inappropriate medication in the elderyTrial Acronym. drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00... (first received 05 April 2012).
DRKS00012246 {unpublished data only}
    1. DRKS00012246. SiMbA‐ Optimizing nursing home residents`safety by checking prescribed medication. apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00012246 (first received 16 May 2017).
DRKS00013588 {unpublished data only}
    1. DRKS00013588. HIOPP‐3‐iTBX: Appropriate and safe medication for nursing home residents using an interdisciplinary toolbox (AMTS‐Toolbox). drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00... (first received 25 January 2018).
Husebo 2015 {published data only}
    1. Husebo BS, Flo E, Aarsland D, Selbaek G, Testad I, Gulla C, et al. COSMOS ‐ improving the quality of life in nursing home patients: protocol for an effectiveness‐implementation cluster randomized clinical hybrid trial. Implementation Science 2015;10:131. - PMC - PubMed
ISRCTN18427377 {unpublished data only}
    1. ISRCTN18427377. Hospital discharge study. isrctn.com/ISRCTN18427377?q=&filters=&sort=&offset=3&tot... 2018; Vol. (first received 03 January 2018).
Jäger 2013 {published data only}
    1. Jäger C, Freund T, Steinhäuser J, Joos S, Wensing M, Szecsenyi J. A tailored implementation intervention to implement recommendations addressing polypharmacy in multimorbid patients: study protocol of a cluster randomized controlled trial. Trials 2013;14(1):1. - PMC - PubMed
Johansen 2018 {published data only}
    1. Johansen JS, Havnes K, Halvorsen KH, Haustreis S, Skaue LW, Kamycheva E, et al. Interdisciplinary collaboration across secondary and primary care to improve medication safety in the elderly (IMMENSE study): study protocol for a randomised controlled trial. BMJ Open 2018;8(1):e020106. - PMC - PubMed
    1. NCT02816086. A new interdisciplinary collaboration structure to improve medication safety in the elderly. clinicaltrials.gov/ct2/show/NCT02816086 (first received 28 June 2016).
Kua 2017 {published and unpublished data}
    1. Kua CH, Yeo C YY, Char CWT, Tan CWY, Tan PC, Mak VS, et al. Nursing home team‐care deprescribing study: a stepped‐wedge randomised controlled trial protocol. BMJ Open 2017;7(5):e015293. - PMC - PubMed
    1. NCT02863341. Nursing Home Team‐Care Deprescribing Study. clinicaltrials.gov/ct2/show/NCT02863341 2018; Vol. (first received 11 August 2016).
Loffler 2014 {published data only}
    1. Loffler C, Drewelow E, Paschka S D, Frankenstein M, Eger J, Jatsch L, et al. Optimizing polypharmacy among elderly hospital patients with chronic diseases: Study protocol of the cluster randomized controlled POLITE‐RCT trial. Implementation science 2014;9:151. - PMC - PubMed
McCarthy 2017 {published and unpublished data}
    1. ISRCTN12752680. Supporting medicines management in older adults with multiple medical conditions. isrctn.com/ISRCTN12752680?q=&filters=&sort=&offset=1&tot... (first received 26 September 2016).
    1. McCarthy C, Clyne B, Corrigan D, Boland F, Wallace E, Moriarty F, et al. Supporting prescribing in older people with multimorbidity and significant polypharmacy in primary care (SPPiRE): a cluster randomised controlled trial protocol and pilot. Implementation Science 2017;12(1):99. - PMC - PubMed
Mestres 2017 {published data only}
    1. Mestres Gonzalvo C, Wit HA, Oijen BP, Hurkens KP, Janknegt R, Schols JM, et al. Supporting clinical rules engine in the adjustment of medication (SCREAM): protocol of a multicentre, prospective, randomised study. BMC Geriatrics 2017;17(1):35. - PMC - PubMed
NCT00844025 {unpublished data only}
    1. NCT00844025. Pharmaceutical care and clinical outcomes for the elderly taking potentially inappropriate medication. clinicaltrials.gov/ct2/show/NCT00844025 (first received 13 February 2009).
NCT01034761 {unpublished data only}
    1. NCT01034761. Using clinical alerts to decrease inappropriate medication prescribing. clinicaltrials.gov/ct2/show/NCT01034761 (first received 17 December 2009).
NCT01534559 {unpublished data only}
    1. NCT01534559. Pharmacist‐led Medicines Management Outpatient Service (MMC). clinicaltrials.gov/ct2/show/NCT01534559 (first received 16 February 2012).
NCT01578525 {unpublished data only}
    1. NCT01578525. Medication safety of elderly patients in hospital and ambulatory setting. clinicaltrials.gov/ct2/show/NCT01578525 (first received 17 April 2012).
NCT02942927 {published and unpublished data}
    1. NCT02942927. Team approach to polypharmacy evaluation and reduction. clinicaltrials.gov/ct2/show/NCT02942927 (first received 24 October 2016).
NCT02986425 {unpublished data only}
    1. NCT02986425. OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid older people (OPERAM). clinicaltrials.gov/ct2/show/NCT02986425 Vol. (first received 08 December 2016).
    1. NTR6012. OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly. trialregister.nl/trialreg/admin/rctview.asp?TC=6012 Vol. (first received 28 July 2016).
NCT03156348 {unpublished data only}
    1. NCT03156348. Impact of clinical pharmacist on adverse drug events in older adults. clinicaltrials.gov/ct2/show/NCT03156348 Vol. (first received 17 May 2017).
NCT03298386 {unpublished data only}
    1. NCT03298386. Elderly Appropriate Treatment in primary care (EAT). clinicaltrials.gov/ct2/show/NCT03298386 Vol. (first received 02 October 2017).
NTR5750 {unpublished data only}
    1. NTR5750. PROPOSE : PReoperative Optimization of Pharmacotherapy in frail Older patients with use of STRIP assistant. trialregister.nl/trialreg/admin/rctview.asp?TC=5750 Vol. (first received 12 February 2016).
Prados‐Torres 2017 {published and unpublished data}
    1. NCT02866799. Multi‐PAP RCT: Improving prescription in primary care patients with multimorbidity andpPolypharmacy. clinicaltrials.gov/ct2/show/NCT02866799 (first received 15 August 2016).
    1. Prados‐Torres A, Cura‐Gonzalez I, Prados‐Torres D, Lopez‐Rodriguez JA, Leiva‐Fernandez F, Calderon‐Larranaga A, et al. Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy: study protocol of a cluster randomized clinical trial (Multi‐PAP project). Implementation Science 2017;12(1):54. - PMC - PubMed
Romskaug 2017 {published data only}
    1. Romskaug R, Molden E, Straand J, Kersten H, Skovlund E, Pitkala KH, et al. Cooperation between geriatricians and general practitioners for improved pharmacotherapy in home‐dwelling elderly people receiving polypharmacy ‐ the COOP Study: study protocol for a cluster randomised controlled trial. Trials 2017;18(1):158. - PMC - PubMed
Selic 2016 {published data only}
    1. Cedilnik Gorup E, Petek‐Ster M. Use of web‐based application to improve prescribing in home‐living elderly: A randomised controlled study protocol. 9th Congress of the European Union Geriatric Medicine Society, Venice, Italy. 2013.
    1. Selic P, Gorup EC, Gorup S, Ster MP, Rifel J, Ketis ZK. The effects of a web application and medical monitoring on the quality of medication, adverse drug events and adherence in the elderly living at home: a protocol of the study. Materia Socio Medica 2016;28(6):432‐6. - PMC - PubMed

Additional references

Agbabiaka 2017
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AGS 2012
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Alldred 2016
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Basger 2012
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Beers 1991
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Beers 1997
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Bradley 2012
    1. Bradley MC, Fahey T, Cahir C, Bennett K, O'Reilly D, Parsons C, et al. Potentially inappropriate prescribing and cost outcomes for older people: A cross‐sectional study using the Northern Ireland Enhanced Prescribing Database. European Journal of Clinical Pharmacology 2012;68(10):1425‐33. - PubMed
Burt 2016
    1. Burt J, Elmore N, Rodgers S, Payne R. Systematic Review protocol: Developing and evaluating a measure of inappropriate polypharmacy in primary care. Available from www.crd.york.ac.uk/PROSPEROFILES/49176_PROTOCOL_20160910.pdf (accessed 10 August 2017).
Bushardt 2008
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Cadogan 2016
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References to other published versions of this review

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