Interventions for enhancing medication adherence
Open accessAbstract
BACKGROUND: People who are prescribed self administered medications typically take only about half their prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications. OBJECTIVES: The primary objective of this review is to assess the effects of interventions intended to enhance patient adherence to prescribed medications for medical conditions, on both medication adherence and clinical outcomes. SEARCH METHODS: We updated searches of The Cochrane Library, including CENTRAL (via http://onlinelibrary.wiley.com/cochranelibrary/search/), MEDLINE, EMBASE, PsycINFO (all via Ovid), CINAHL (via EBSCO), and Sociological Abstracts (via ProQuest) on 11 January 2013 with no language restriction. We also reviewed bibliographies in articles on patient adherence, and contacted authors of relevant original and review articles. SELECTION CRITERIA: We included unconfounded RCTs of interventions to improve adherence with prescribed medications, measuring both medication adherence and clinical outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive findings at earlier time points. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data and a third author resolved disagreements. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Pooling results according to one of these characteristics still leaves highly heterogeneous groups, and we could not justify meta-analysis. Instead, we conducted a qualitative analysis with a focus on the RCTs with the lowest risk of bias for study design and the primary clinical outcome. MAIN RESULTS: The present update included 109 new RCTs published since the previous update in January 2007, bringing the total number of RCTs to 182; we found five RCTs from the previous update to be ineligible and excluded them. Studies were heterogeneous for patients, medical problems, treatment regimens, adherence interventions, and adherence and clinical outcome measurements, and most had high risk of bias. The main changes in comparison with the previous update include that we now: 1) report a lack of convincing evidence also specifically among the studies with the lowest risk of bias; 2) do not try to classify studies according to intervention type any more, due to the large heterogeneity; 3) make our database available for collaboration on sub-analyses, in acknowledgement of the need to make collective advancement in this difficult field of research. Of all 182 RCTs, 17 had the lowest risk of bias for study design features and their primary clinical outcome, 11 from the present update and six from the previous update. The RCTs at lowest risk of bias generally involved complex interventions with multiple components, trying to overcome barriers to adherence by means of tailored ongoing support from allied health professionals such as pharmacists, who often delivered intense education, counseling (including motivational interviewing or cognitive behavioral therapy by professionals) or daily treatment support (or both), and sometimes additional support from family or peers. Only five of these RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were apparent. Even the most effective interventions did not lead to large improvements in adherence or clinical outcomes. AUTHORS' CONCLUSIONS: Across the body of evidence, effects were inconsistent from study to study, and only a minority of lowest risk of bias RCTs improved both adherence and clinical outcomes. Current methods of improving medication adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. The research in this field needs advances, including improved design of feasible long-term interventions, objective adherence measures, and sufficient study power to detect improvements in patient-important clinical outcomes. By making our comprehensive database available for sharing we hope to contribute to achieving these advances.
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Current methods of improving medication adherence for chronic health problems are mostly complex and not effective.
“Although there is a wealth of controlled trials on interventions to improve adherence, current methods of improving medication adherence for chronic health problems are mostly complex and not effective [2,3,4].”
From Factors Contributing to Medication Adherence in Patients with a Chronic Condition: A Scoping Review of Qualitative Research (2021) · cites this paper as [3]
Other CF-related reviews and general adherence reviews have highlighted the limitations of many included trials in terms of having small sample sizes and being underpowered to detect a meaningful difference in adherence.
“This review is in agreement with other, CF-related reviews and general adherence reviews, which have highlighted the limitations of many included trials in terms of having small sample sizes and being underpowered to detect a meaningful difference in adherence (Goldbeck 2014; Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
Previous Cochrane Reviews on adherence and CF-specific reviews have not used a coding framework, so this review has improved on existing methodologies.
“Previous Cochrane Reviews on adherence (Nieuwlaat 2014) and CF-specific reviews (Goldbeck 2014; Savage 2014) have not used a coding framework, so this review has improved on existing methodologies.”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
Given the complexity of many adherence interventions tested to date and the way complex interventions are reported, it is often difficult to determine the content or active ingredients of effective interventions that bring about change.
“Given the complexity of many adherence interventions tested to date (Nieuwlaat 2014), and the way in which complex interventions are reported or described in the literature, it is o en difficult to determine the content, or the 'active ingredients', of effective interventions that bring about change (Michie 2009).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
Understanding the active ingredients of promising interventions will make it easier to replicate effective interventions, reduce the potential waste of time and resources on trials of ineffective techniques, and inform adherence research in the future.
“Understanding the 'active ingredients' of promising interventions will make it easier to replicate effective interventions; will reduce the potential waste of time and resources on trials of ineffective techniques (Michie 2009); and will inform adherence research in the future (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
A previous Cochrane Review highlighted likely inclusion bias in adherence trials, with participants having higher than average adherence at baseline.
“A previous Cochrane Review highlighted likely inclusion bias in adherence trials, with participants having higher than average adherence at baseline (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
Underpowered trials are more likely to miss a meaningful difference in adherence, even when improving adherence substantially, and showing an effect on clinical outcomes is likely even harder.
“Underpowered trials are more likely to miss a meaningful difference in adherence, even when improving adherence substantially, and showing an effect on clinical outcomes is likely even harder (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
Interventions that specifically aim to improve adherence to prescribed medications vary widely.
“Interventions that specifically aim to improve adherence to prescribed medications vary widely (Nieuwlaat 2014).”
From Psychological interventions for improving adherence to inhaled therapies in people with cystic fibrosis (2023) · cites this paper as Nieuwlaat 2014
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British Guideline on the Management of Asthma
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Medication Adherence: WHO Cares?
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2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
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Medication Adherence: Its Importance in Cardiovascular Outcomes
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“Patients will not take drugs unless they perceive a need to do so, particularly when asymptomatic (DiMatteo et al., 2002; Haynes et al., 2008).”
Carey, R. M., Calhoun, D. A., Bakris, G. L., Brook, R. D., Daugherty, S. L., Dennison-Himmelfarb, C. R., Egan, B. M., Flack, J. M., Gidding, S. S., Judd, E., et al. (2018) · Hypertension · doi:10.1161/hyp.0000000000000084 · Cited by 1,153 · see citing works
“varied, solutions to improve adherence at the population level must be multifactorial.(108,111,112)”
BackgroundWhelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000596 · Cited by 1,127 · see citing works
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Determinants of patient adherence: a review of systematic reviews
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Polonsky, W., & Henry, R. (2016) · Patient Preference and Adherence · doi:10.2147/ppa.s106821 · Cited by 784 · see citing works
“65 A key element is the need for greater consistency when measuring medication adherence, which require better instruments and tools for assessment.”
Burstein, H. J., Prestrud, A. A., Seidenfeld, J., Anderson, H., Buchholz, T. A., Davidson, N. E., Gelmon, K. A., Giordano, S. H., Hudis, C. A., Malin, J. L., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.3756 · Cited by 794 · see citing works
National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2
Jacobson, T. A., Maki, K. C., Orringer, C. E., Jones, P. H., Kris-Etherton, P., Sikand, G., La Forge, R., Daniels, S. R., Wilson, D. P., Morris, P. B., et al. (2015) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2015.09.002 · Cited by 784 · see citing works
“Researchers report that approximately 70–90% of opportunities for a health care provider to express empathy to a patient are missed.(764,772,785,786) Patients often do not realize that there may not be an immediate benefit of therapy, which leads to their being frustrated and not adhering to, or failing to persist in…”
BackgroundAdherence in Hypertension: A Review of Prevalence, Risk Factors, Impact, and Management
Burnier, M., & Egan, B. M. (2019) · Circulation Research · doi:10.1161/circresaha.118.313220 · Cited by 878 · see citing works
Viswanathan, M., Golin, C. E., Jones, C. D., Ashok, M., Blalock, S. J., Wines, R. C. M., Coker-Schwimmer, E. J. L., Rosen, D. L., Sista, P., & Lohr, K. N. (2012) · Annals of Internal Medicine · doi:10.7326/0003-4819-157-11-201212040-00538 · Cited by 754 · see citing works
Interventions to improve the appropriate use of polypharmacy for older people
Patterson, S. M., Cadogan, C. A., Kerse, N. M., Cardwell, C. R., Bradley, M. C., Ryan, C. A., & Hughes, C. M. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008165.pub3 · Cited by 759 · see citing works
Mobile Telephone Text Messaging for Medication Adherence in Chronic Disease: A Meta-analysis
Thakkar, J., Kurup, R., Laba, T.-L., Santo, K., Thiagalingam, A., Rodgers, A., Woodward, M., Redfern, J., & Chow, C. K. (2016) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2015.7667 · Cited by 685 · see citing works
Adherence to Therapies in Patients with Type 2 Diabetes
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ESC/EAS Guidelines for the management of dyslipidaemias
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Shared Treatment Decision Making Improves Adherence and Outcomes in Poorly Controlled Asthma
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Barnes, T. R. E., Drake, R., Paton, C., Cooper, S. J., Deakin, J. F. W., Ferrier, I. N., Gregory, C. J., Haddad, P. M., Howes, O. D., Jones, I. R., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119889296 · Cited by 607 · see citing works
Rathbone, A. L., & Prescott, J. (2017) · Journal of Medical Internet Research · doi:10.2196/jmir.7740 · Cited by 497 · see citing works
“Medication nonadherence is a common health care problem and has the ability to impact a patient’s health, the doctor patient relationship, and become an increasing burden on health care settings such as general practitioners (GPs) and hospitals due to increase in attendance [82].”
BackgroundOsteoporosis: burden, health care provision and opportunities in the EU
Ström, O., Borgström, F., Kanis, J. А., Compston, J. E., Cooper, C. C., McCloskey, E. V., & Jönsson, B. (2011) · Archives of Osteoporosis · doi:10.1007/s11657-011-0060-1 · Cited by 550 · see citing works
Roth, D. E., Abrams, S. A., Aloia, J. F., Bergeron, G., Bourassa, M. W., Brown, K. H., Calvo, M. S., Cashman, K. D., Combs, G. F., De‐Regil, L. M., et al. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13968 · Cited by 528 · see citing works
Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems
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Interventions to Support Behavioral Self-Management of Chronic Diseases
Allegrante, J. P., Wells, M. T., & Peterson, J. C. (2019) · Annual Review of Public Health · doi:10.1146/annurev-publhealth-040218-044008 · Cited by 502 · see citing works
Kvarnström, K., Westerholm, A., Airaksinen, M., & Liira, H. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13071100 · Cited by 470 · see citing works
“have combined the existing evidence of adherence interventions [3].”
BackgroundInterventions to improve adherence to exercise for chronic musculoskeletal pain in adults.
Jordan, J. L., Holden, M., Mason, E. E., & Foster, N. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005956.pub2 · Cited by 166 · see citing works
Patient Characteristics Associated with Medication Adherence
Rolnick, S. J., Pawloski, P. A., Hedblom, B. D., Asche, S. E., & Bruzek, R. J. (2013) · Clinical Medicine & Research · doi:10.3121/cmr.2013.1113 · Cited by 481 · see citing works
Smartphone medication adherence apps: Potential benefits to patients and providers
Dayer, L. E., Heldenbrand, S. D., Anderson, P., Gubbins, P. O., & Martin, B. C. (2013) · Journal of the American Pharmacists Association · doi:10.1331/japha.2013.12202 · Cited by 474 · see citing works
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Medication adherence: a call for action
Bosworth, H. B., Granger, B. B., Mendys, P., Brindis, R., Burkholder, R., Czajkowski, S. M., Daniel, J. G., Ekman, I., Ho, M., Johnson, M., et al. (2011) · American Heart Journal · doi:10.1016/j.ahj.2011.06.007 · Cited by 448 · see citing works
Medication Adherence: Truth and Consequences
Brown, M. T., Bussell, J. K., Dutta, S., Davis, K., Strong, S., & Mathew, S. C. (2016) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2016.01.010 · Cited by 425 · see citing works
“A review of 78 randomized trials found relatively few complex interventions and no one simple intervention to improving long-term medication adherence and health outcomes.(70) A variety of approaches are necessary.”
Blaschke, T. F., Osterberg, L. G., Vrijens, B., & Urquhart, J. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011711-113247 · Cited by 420 · see citing works
What are validated self-report adherence scales really measuring?: a systematic review
Nguyen, T., Caze, A. L., & Cottrell, N. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12194 · Cited by 431 · see citing works
Frost, H., Campbell, P., Maxwell, M., O’Carroll, R. E., Dombrowski, S. U., Williams, B., Cheyne, H., Coles, E., & Pollock, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0204890 · Cited by 420 · see citing works
Hugtenburg, J. G., Vervloet, M., van Dijk, L., Timmers, L., & Elders, P. J. M. (2013) · Patient Preference and Adherence · doi:10.2147/ppa.s29549 · Cited by 402 · see citing works
Hankey, G. J. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70255-2 · Cited by 392 · see citing works
Improving health outcomes with better patient understanding and education
Adams, R. (2010) · Risk Management and Healthcare Policy · doi:10.2147/rmhp.s7500 · Cited by 384 · see citing works
Wozniak, D. R., Lasserson, T. J., & Smith, I. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007736.pub2 · Cited by 380 · see citing works
Pharmacist services provided in general practice clinics: A systematic review and meta-analysis
Tan, E. C. K., Stewart, K., Elliott, R. A., & George, J. (2013) · Research in Social and Administrative Pharmacy · doi:10.1016/j.sapharm.2013.08.006 · Cited by 374 · see citing works
Medication adherence outcomes of 771 intervention trials: Systematic review and meta-analysis
Conn, V. S., & Ruppar, T. M. (2017) · Preventive Medicine · doi:10.1016/j.ypmed.2017.03.008 · Cited by 367 · see citing works
“Although measuring adherence is challenging, the continued use of self-report measures is unfortunate because their imprecise nature may obscure group differences (Culig and Leppee, 2014; Haynes et al., 2008; Lehmann et al., 2014).”
BackgroundNeugut, A. I., Subar, M., Wilde, E. T., Stratton, S., Brouse, C. H., Hillyer, G. C., Grann, V. R., & Hershman, D. L. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.3179 · Cited by 354 · see citing works
Choudhry, N. K., Kronish, I. M., Vongpatanasin, W., Ferdinand, K. C., Pavlik, V. N., Egan, B. M., Schoenthaler, A., Houston Miller, N., Hyman, D. J., & on behalf of the American Heart Association Council on Hypertension; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology (2022) · Hypertension · doi:10.1161/hyp.0000000000000203 · Cited by 349 · see citing works
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Effect of outpatient pharmacists' non-dispensing roles on patient outcomes and prescribing patterns
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ESPACOMP Medication Adherence Reporting Guideline (EMERGE)
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“EMERGE was developed to help researchers improve the often methodologically weak (8, 35, 36) and suboptimum reporting of medication adherence research (11–13).”
BackgroundBrieger, D. B., Amerena, J. V., Attia, J., Bajorek, B. V., Chan, K. H., Connell, C., Freedman, B., Ferguson, C., Hall, T. L., Haqqani, H. M., et al. (2018) · Heart Lung and Circulation · doi:10.1016/j.hlc.2018.06.1043 · Cited by 328 · see citing works
“Unfortunately, the most effective interventions are usually complex (comprising tailored ongoing support, cognitive behavioural therapy, motivational interviewing, education, or daily treatment support; which are delivered face-to-face, often via pharmacists) and may be difficult to implement in real-world practice [4…”
Mobile phone messaging for preventive health care
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“Incomplete medication adherence is well known, even in the highly structured clinical trial setting [26, 27].”
BackgroundInterventional tools to improve medication adherence: review of literature
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“This ambiguity mirrors the conclusions made in numerous systematic reviews 23,80–82 in relation to the effectiveness of the majority of adherence enhancing interventions.”
BackgroundNonadherence Consensus Conference Summary Report
Fine, R. Ν., Becker, Y. T., Geest, S. D., Eisen, H. J., Ettenger, R. B., Evans, R., Rudow, D. L., McKay, D. B., Neu, A. M., Nevins, T. E., et al. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02495.x · Cited by 297 · see citing works
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“Moreover, complex multifactorial strategies, addressing different barriers have been mostly assessed without previous evaluation of their individual components [59].”
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The Unmet Challenge of Medication Nonadherence
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Medication Adherence to Multidrug Regimens
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“Attempts to correct such beliefs have had mixed results [87 – 89], but several studies have indicated that necessity beliefs and concerns are amenable to change [90 – 92].”
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A Systematic Review of Medication Adherence Thresholds Dependent of Clinical Outcomes
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“, adherence rate) and varies from 0% to over 100% in literature (DiMatteo, 2004; Briesacher et al., 2008; Fischer et al., 2010; Nieuwlaat et al., 2014; Huurne et al., 2015).”
BackgroundSelf-citationRisk Factors for Nonadherence to Antihypertensive Treatment
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“It is known that current interventions provide inconsistent results in improving adherence [5].”
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Non-adherence to cardiovascular medications
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“Treatment-, patient-, and healthcare system-related factors all influence adherence (Table 2).(6,24,52) While prediction remains challenging, new technologies and data repositories promise to yield approaches to better manage the highly individualized nature of nonadherence.”
BackgroundA systematic review of medication non-adherence in persons with dementia or cognitive impairment
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Interventions to improve adherence to antiretroviral therapy
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- Authors
- Nieuwlaat, R., Wilczynski, N., Navarro, T., Hobson, N., Jeffery, R., Keepanasseril, A., Agoritsas, T., Mistry, N., Iorio, A., Jack, S., Sivaramalingam, B., Iserman, E., Mustafa, R. A., Jedraszewski, D., Cotoi, C., & Haynes, R. B.
- Affiliations
- Hamilton General Hospital (CA)
- McMaster University (CA)
- St. Michael's Hospital (CA)
- University of Guelph (CA)
- ORCID
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2014-11-20
- Volume
- 2014
- Issue
- 11
- Pages
- CD000011-CD000011
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC7263418
- OpenAlex
- W1594567624
- Cited by
- 2,945
- References
- 645
- Citations by year
- 2026: 64 · 2025: 119 · 2024: 108 · 2023: 147 · 2022: 157 · 2021: 177 · 2020: 200 · 2019: 190 · 2018: 209 · 2017: 244 · 2016: 224 · 2015: 191 · 2014: 214 · 2013: 186 · 2012: 124
- FWCI
- 37.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacy and Medical Practices
- Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
- Keywords
- medication adherence, adherence interventions, self-administered medication, clinical outcomes, risk of bias, quality of evidence, pill organizers, pharmacists
- MeSH terms
- Drug Therapy, Humans, Patient Education as Topic, Self Administration, Randomized Controlled Trials as Topic, Publication Bias, Medication Adherence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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