Review Article| Volume 19, ISSUE 11, P923-935.e2, November 2018

Deprescribing Medications for Chronic Diseases Management in Primary Care Settings: A Systematic Review of Randomized Controlled Trials

Published:August 11, 2018DOI:



      Perform a systematic review to evaluate the outcome of deprescription compared with standard care. The focus was on chronic medical and mental health conditions managed in primary care.


      The databases searched include PubMed, Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science. Each study was assessed for bias with the Cochrane Collaboration tool.

      Settings and Participants

      This review included outpatient, assisted living, nursing home, and acute care settings (if medications for chronic disease were deprescribed). Subjects were non–terminally ill adults 18 years and older.


      Primary outcome was successful deprescription, defined as a statistically significant reduction in medication burden between the intervention group and the standard care or control group, or when more than 50% of intervention subjects were able to tolerate medication discontinuation compared with control by the end of the study.


      Fifty-eight articles met the study criteria. Thirty-three (58%) had a high risk of bias. Studies varied in duration from 4 weeks to 5 years and were conducted across a diverse array of primary health care settings. The most successful interventions used pharmacist-led educational interventions and patient-specific drug recommendations. Cardiovascular drugs including antihypertensives/diuretics and nitrates were the most successfully deprescribed class of drugs. Psychotropic medications and proton-pump inhibitors were the classes most resistant to deprescribing, despite intense intervention.


      Deprescription may be successful and effective in select classes of drugs, with collaboration of clinical pharmacists for patient and provider education, and patient-specific drug recommendations, complemented by close clinical follow-up to detect early signs of exacerbation of chronic diseases. This review also suggests that deprescription may (1) require expensive intensive, ongoing interventions by clinical teams; (2) not lead to expected outcomes such as improved falls rate, cognition, and quality of life, or a lower admission rate; and (3) have unexpected adverse outcomes affecting patients’ quality of life.


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      1. Health, United States, 2016: With Chartbook on Long-term Trends in Health.

        • Reeve E.
        • Gnjidic D.
        • Long J.
        • Hilmer S.
        A systematic review of the emerging definition of “deprescribing” with network analysis: Implications for future research and clinical practice.
        Br J Clin Pharmacol. 2015; 80: 1254-1268
        • Garfinkel D.
        • Mangin D.
        Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: Addressing polypharmacy.
        Arch Intern Med. 2010; 170: 1648-1654
        • Iyer S.
        • Naganathan V.
        • McLachlan A.J.
        • Le Couteur D.G.
        Medication withdrawal trials in people aged 65 years and older: A systematic review.
        Drugs Aging. 2008; 25: 1021-1031
        • Wallis K.A.
        • Andrews A.
        • Henderson M.
        Swimming against the tide: Primary care physicians' views on deprescribing in everyday practice.
        Ann Fam Med. 2017; 15: 341-346
        • Levine G.N.
        • Bates E.R.
        • Bittl J.A.
        • et al.
        2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery.
        Circulation. 2016; 134: e123-e155
        • Kearon C.
        • Akl E.A.
        • Ornelas J.
        • et al.
        Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.
        Chest. 2016; 149: 315-352
        • Page A.T.
        • Clifford R.M.
        • Potter K.
        • et al.
        The feasibility and effect of deprescribing in older adults on mortality and health: A systematic review and meta-analysis.
        Br J Clin Pharmacol. 2016; 82: 583-623
        • Adams M.L.
        Differences between younger and older US adults with multiple chronic conditions.
        Prev Chronic Dis. 2017; 14: E76
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • et al.
        Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement.
        PLoS Med. 2009; 6: e1000097
        • Pitkala K.H.
        • Juola A.L.
        • Kautiainen H.
        • et al.
        Education to reduce potentially harmful medication use among residents of assisted living facilities: A randomized controlled trial.
        J Am Med Dir Assoc. 2014; 15: 892-898
        • Garcia-Gollarte F.
        • Baleriola-Julvez J.
        • Ferrero-Lopez I.
        • et al.
        An educational intervention on drug use in nursing homes improves health outcomes resource utilization and reduces inappropriate drug prescription.
        J Am Med Dir Assoc. 2014; 15: 885-891
        • Blalock S.J.
        • Casteel C.
        • Roth M.T.
        • et al.
        Impact of enhanced pharmacologic care on the prevention of falls: A randomized controlled trial.
        Am J Geriatr Pharmacother. 2010; 8: 428-440
        • Bryant L.J.
        • Coster G.
        • Gamble G.D.
        • McCormick R.N.
        The General Practitioner-Pharmacist Collaboration (GPPC) study: A randomised controlled trial of clinical medication reviews in community pharmacy.
        Int J Pharm Pract. 2011; 19: 94-105
        • Lampela P.
        • Hartikainen S.
        • Lavikainen P.
        • et al.
        Effects of medication assessment as part of a comprehensive geriatric assessment on drug use over a 1-year period: A population-based intervention study.
        Drugs Aging. 2010; 27: 507-521
        • Allard J.
        • Hebert R.
        • Rioux M.
        • et al.
        Efficacy of a clinical medication review on the number of potentially inappropriate prescriptions prescribed for community-dwelling elderly people.
        CMAJ. 2001; 164: 1291-1296
        • Lenander C.
        • Elfsson B.
        • Danielsson B.
        • et al.
        Effects of a pharmacist-led structured medication review in primary care on drug-related problems and hospital admission rates: A randomized controlled trial.
        Scand J Prim Health Care. 2014; 32: 180-186
        • Dalleur O.
        • Boland B.
        • Losseau C.
        • et al.
        Reduction of potentially inappropriate medications using the STOPP criteria in frail older inpatients: A randomised controlled study.
        Drugs Aging. 2014; 31: 291-298
        • Michalek C.
        • Wehling M.
        • Schlitzer J.
        • Frohnhofen H.
        Effects of “Fit fOR The Aged” (FORTA) on pharmacotherapy and clinical endpoints—A pilot randomized controlled study.
        Eur J Clin Pharmacol. 2014; 70: 1261-1267
        • Potter K.
        • Flicker L.
        • Page A.
        • Etherton-Beer C.
        Deprescribing in frail older people: A randomised controlled trial.
        PLoS One. 2016; 11: e0149984
        • Crotty M.
        • Rowett D.
        • Spurling L.
        • et al.
        Does the addition of a pharmacist transition coordinator improve evidence-based medication management and health outcomes in older adults moving from the hospital to a long-term care facility? Results of a randomized, controlled trial.
        Am J Geriatr Pharmacother. 2004; 2: 257-264
        • Frankenthal D.
        • Lerman Y.
        • Kalendaryev E.
        • Lerman Y.
        Intervention with the screening tool of older persons potentially inappropriate prescriptions/screening tool to alert doctors to right treatment criteria in elderly residents of a chronic geriatric facility: A randomized clinical trial.
        J Am Geriatr Soc. 2014; 62: 1658-1665
        • Furniss L.
        • Burns A.
        • Craig S.K.
        • et al.
        Effects of a pharmacist's medication review in nursing homes. Randomised controlled trial.
        Br J Psychiatry. 2000; 176: 563-567
        • Kersten H.
        • Molden E.
        • Tolo I.K.
        • et al.
        Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: A randomized controlled trial.
        J Gerontol A Biol Sci Med Sci. 2013; 68: 271-278
        • Hanlon J.T.
        • Weinberger M.
        • Samsa G.P.
        • et al.
        A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy.
        Am J Med. 1996; 100: 428-437
        • Bonnet-Zamponi D.
        • d'Arailh L.
        • Konrat C.
        • et al.
        Drug-related readmissions to medical units of older adults discharged from acute geriatric units: Results of the Optimization of Medication in AGEd multicenter randomized controlled trial.
        J Am Geriatr Soc. 2013; 61: 113-121
        • Roberts M.S.
        • Stokes J.A.
        • King M.A.
        • et al.
        Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes.
        Br J Clin Pharmacol. 2001; 51: 257-265
        • Crotty M.
        • Halbert J.
        • Rowett D.
        • et al.
        An outreach geriatric medication advisory service in residential aged care: A randomised controlled trial of case conferencing.
        Age Ageing. 2004; 33: 612-617
        • Tinetti M.E.
        • Baker D.I.
        • McAvay G.
        • et al.
        A multifactorial intervention to reduce the risk of falling among elderly people living in the community.
        N Engl J Med. 1994; 331: 821-827
        • Clyne B.
        • Smith S.M.
        • Hughes C.M.
        • et al.
        Effectiveness of a multifaceted intervention for potentially inappropriate prescribing in older patients in primary care: A cluster-randomized controlled trial (OPTI-SCRIPT Study).
        Ann Fam Med. 2015; 13: 545-553
        • Ballard C.
        • Hanney M.L.
        • Theodoulou M.
        • et al.
        The dementia antipsychotic withdrawal trial (DART-AD): Long-term follow-up of a randomised placebo-controlled trial.
        Lancet Neurol. 2009; 8: 151-157
        • Ballard C.G.
        • Thomas A.
        • Fossey J.
        • et al.
        A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: The neuropsychiatric inventory median cutoff is a predictor of clinical outcome.
        J Clin Psychiatry. 2004; 65: 114-119
        • Devanand D.P.
        • Pelton G.H.
        • Cunqueiro K.
        • et al.
        A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease.
        Int J Geriatr Psychiatry. 2011; 26: 937-943
        • Devanand D.P.
        • Mintzer J.
        • Schultz S.K.
        • et al.
        Relapse risk after discontinuation of risperidone in Alzheimer's disease.
        N Engl J Med. 2012; 367: 1497-1507
        • Ruths S.
        • Straand J.
        • Nygaard H.A.
        • et al.
        Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing home residents with dementia: A randomized, placebo-controlled, double-blinded study. The Bergen District Nursing Home Study.
        J Am Geriatr Soc. 2004; 52: 1737-1743
        • Ruths S.
        • Straand J.
        • Nygaard H.A.
        • Aarsland D.
        Stopping antipsychotic drug therapy in demented nursing home patients: A randomized, placebo-controlled study—The Bergen District Nursing Home Study (BEDNURS).
        Int J Geriatr Psychiatry. 2008; 23: 889-895
        • van Reekum R.
        • Clarke D.
        • Conn D.
        • et al.
        A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia.
        Int Psychogeriatr. 2002; 14: 197-210
        • Ahmed Z.
        • Fraser W.
        • Kerr M.P.
        • et al.
        Reducing antipsychotic medication in people with a learning disability.
        Br J Psychiatry. 2000; 176: 42-46
        • Bridges-Parlet S.
        • Knopman D.
        • Steffes S.
        Withdrawal of neuroleptic medications from institutionalized dementia patients: Results of a double-blind, baseline-treatment-controlled pilot study.
        J Geriatr Psychiatry Neurol. 1997; 10: 119-126
        • Habraken H.
        • Soenen K.
        • Blondeel L.
        • et al.
        Gradual withdrawal from benzodiazepines in residents of homes for the elderly: Experience and suggestions for future research.
        Eur J Clin Pharmacol. 1997; 51: 355-358
        • Tannenbaum C.
        • Martin P.
        • Tamblyn R.
        • et al.
        Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: The EMPOWER cluster randomized trial.
        JAMA Intern Med. 2014; 174: 890-898
        • Cormack M.A.
        • Sweeney K.G.
        • Hughes-Jones H.
        • Foot G.A.
        Evaluation of an easy, cost-effective strategy for cutting benzodiazepine use in general practice.
        Br J Gen Pract. 1994; 44: 5-8
        • Heather N.
        • Bowie A.
        • Ashton H.
        • et al.
        Randomised controlled trial of two brief interventions against long-term benzodiazepine use: Outcome of intervention.
        Addict Res Theory. 2004; 12: 141-154
        • Vicens C.
        • Fiol F.
        • Llobera J.
        • et al.
        Withdrawal from long-term benzodiazepine use: Randomised trial in family practice.
        Br J Gen Pract. 2006; 56: 958-963
        • Zwar N.A.
        • Wolk J.
        • Gordon J.J.
        • Sanson-Fisher R.W.
        Benzodiazepine prescribing by GP registrars. A trial of educational outreach.
        Aust Fam Physician. 2000; 29: 1104-1107
        • Ulfvarson J.
        • Adami J.
        • Wredling R.
        • et al.
        Controlled withdrawal of selective serotonin reuptake inhibitor drugs in elderly patients in nursing homes with no indication of depression.
        Eur J Clin Pharmacol. 2003; 59: 735-740
        • Montgomery S.A.
        • Nil R.
        • Durr-Pal N.
        • et al.
        A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder.
        J Clin Psychiatry. 2005; 66: 1270-1278
        • Kocsis J.H.
        • Schatzberg A.
        • Rush A.J.
        • et al.
        Psychosocial outcomes following long-term, double-blind treatment of chronic depression with sertraline vs placebo.
        Arch Gen Psychiatry. 2002; 59: 723-728
        • Landstedt-Hallin L.
        • Arner P.
        • Lins P.E.
        • et al.
        The role of sulphonylurea in combination therapy assessed in a trial of sulphonylurea withdrawal. Scandinavian Insulin-Sulphonylurea Study Group Research Team.
        Diabet Med. 1999; 16: 827-834
        • Reddel H.K.
        • Gibson P.G.
        • Peters M.J.
        • et al.
        Down-titration from high-dose combination therapy in asthma: Removal of long-acting beta(2)-agonist.
        Respir Med. 2010; 104: 1110-1120
        • Wouters E.F.
        • Postma D.S.
        • Fokkens B.
        • et al.
        Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: A randomised controlled trial.
        Thorax. 2005; 60: 480-487
        • Krol N.
        • Wensing M.
        • Haaijer-Ruskamp F.
        • et al.
        Patient-directed strategy to reduce prescribing for patients with dyspepsia in general practice: A randomized trial.
        Aliment Pharmacol Ther. 2004; 19: 917-922
        • Lampen-Smith A.
        • Young J.
        • O'Rourke M.A.
        • et al.
        Blinded randomised controlled study of the effect of a discharge communication template on proton pump inhibitor prescribing.
        N Z Med J. 2012; 125: 30-36
        • Curtain C.
        • Peterson G.M.
        • Tenni P.
        • et al.
        Outcomes of a decision support prompt in community pharmacy-dispensing software to promote step-down of proton pump inhibitor therapy.
        Br J Clin Pharmacol. 2011; 71: 780-784
        • Zwisler J.E.
        • Jarbol D.E.
        • Lassen A.T.
        • et al.
        Placebo-controlled discontinuation of long-term acid-suppressant therapy: A randomised trial in general practice.
        Int J Family Med. 2015; 2015: 175436
        • Black D.M.
        • Schwartz A.V.
        • Ensrud K.E.
        • et al.
        Effects of continuing or stopping alendronate after 5 years of treatment: The Fracture Intervention Trial Long-term Extension (FLEX): A randomized trial.
        JAMA. 2006; 296: 2927-2938
        • Burr M.L.
        • King S.
        • Davies H.E.
        • Pathy M.S.
        The effects of discontinuing long-term diuretic therapy in the elderly.
        Age Ageing. 1977; 6: 38-45
        • de Jonge J.W.
        • Knottnerus J.A.
        • van Zutphen W.M.
        • et al.
        Short term effect of withdrawal of diuretic drugs prescribed for ankle oedema.
        BMJ. 1994; 308: 511-513
        • Myers M.G.
        • Weingert M.E.
        • Fisher R.H.
        • et al.
        Unnecessary diuretic therapy in the elderly.
        Age Ageing. 1982; 11: 213-221
        • Walma E.P.
        • Hoes A.W.
        • van Dooren C.
        • et al.
        Withdrawal of long-term diuretic medication in elderly patients: A double blind randomised trial.
        BMJ. 1997; 315: 464-468
        • Moonen J.E.
        • Foster-Dingley J.C.
        • de Ruijter W.
        • et al.
        Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: The DANTE Study Leiden.
        Age Ageing. 2016; 45: 249-255
        • George J.
        • Kitzis I.
        • Zandorf D.
        • et al.
        Safety of nitrate withdrawal in angina-free and hemodynamically stable patients with coronary artery disease.
        Chest. 2003; 124: 1652-1657
        • Lemos K.F.
        • Rabelo-Silva E.R.
        • Ribeiro L.W.
        • et al.
        Effect of nitrate withdrawal on quality of life and adherence to treatment in patients with stable angina: Evidence from a randomized clinical trial.
        Coron Artery Dis. 2014; 25: 215-223
        • Tse W.
        • Frisina P.G.
        • Halbig T.D.
        • et al.
        The effects of withdrawal of dopaminergic medication in nursing home patients with advanced parkinsonism.
        J Am Med Dir Assoc. 2008; 9: 670-675
        • Beer C.
        • Loh P.K.
        • Peng Y.G.
        • et al.
        A pilot randomized controlled trial of deprescribing.
        Ther Adv Drug Saf. 2011; 2: 37-43
        • Campbell A.J.
        • Robertson M.C.
        • Gardner M.M.
        • et al.
        Psychotropic medication withdrawal and a home-based exercise program to prevent falls: A randomized, controlled trial.
        J Am Geriatr Soc. 1999; 47: 850-853
        • Cohen-Mansfield J.
        • Lipson S.
        • Werner P.
        • et al.
        Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: A controlled, double-blind study.
        Arch Intern Med. 1999; 159: 1733-1740
        • Patterson S.M.
        • Hughes C.M.
        • Crealey G.
        • et al.
        An evaluation of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in Northern Ireland (Fleetwood Northern Ireland Study).
        J Am Geriatr Soc. 2010; 58: 44-53
      2. Oxford Centre for Evidence-based Medicine – Levels of Evidence (March 2009).
        (Available at:)
        • Jones A.
        The National Nursing Home Survey: 1999 summary.
        Vital Health Stat. 2002; 13: 1-116