Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

Concurrent use of prescription drugs and herbal medicinal products in older adults: a systematic review protocol

  • Taofikat Agbabiaka1, 2,
  • Barbara Wider3Email author,
  • Leala Kay Watson3 and
  • Claire Goodman1
Systematic Reviews20165:65

DOI: 10.1186/s13643-016-0244-2

Received: 5 January 2016

Accepted: 13 April 2016

Published: 21 April 2016

Abstract

Background

There has been a global increase in the use of herbal medicinal products (HMPs). About a quarter of UK adults use HMPs, bought over the counter by self-prescription and often not disclosed to healthcare professionals. Potential herb-drug interaction is a clinical concern, with older people at greater risk because of co-morbidities and slower clearance of pharmacologically active compounds. While there is a good understanding of general herbal medicine use by older people, less is known about the extent and implications of concurrent use with prescription medicines. The aim of this systematic review is to assess the prevalence, patterns, safety issues and other factors associated with concurrent prescription and herbal medicines use among older adults.

Methods/design

Systematic electronic searches of MEDLINE, PsychINFO, Excerpta Medica dataBASE (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Web of Science and Cochrane from inception till present for studies reporting the concurrent use of prescription medicines with HMPs in older adults (≥65 years). Lateral searching via related citation (PubMed) and checking reference lists of identified studies will be performed. Two reviewers will independently screen studies, extract data and appraise methodological quality using the Joanna Briggs Institute checklist for prevalence data and the Critical Appraisal Skills Programme (CASP) checklist. Qualitative and quantitative studies from all settings will be included. Non-empirical papers, in vitro experiments and animal studies will be excluded. Primary outcomes are prevalence and patterns of concurrent use, number and types of prescription and HMPs and adverse reactions reported. Secondary outcomes are disclosure of HMP use to healthcare professionals and cost of HMPs. A narrative synthesis of included studies will be performed to summarise the evidence.

Discussion

This review will synthesise and critically appraise current knowledge on the concurrent use of drugs and HMPs by older adults and thus provide a better understanding of the issue. It will also identify any gaps in knowledge. By establishing safety issues associated with concurrent use, it will also inform strategies that can help practitioners to identify and manage older people at potential risk of herb-drug interactions.

Systematic review registration

PROSPERO CRD42014009091

Keywords

Concurrent use Herbal medicinal product Prescription drug Prevalence Herb-drug interaction Adverse reaction Safety Elderly

Background

The last two decades have witnessed a global increase in the use of herbal medicinal products (HMPs) [1]. Herbal medicinal product is described as “any medicinal product, exclusively containing as active ingredients one or more herbal substances or one or more herbal preparations, or one or more such herbal substances in combination with one or more such herbal preparations” [2]. High prevalence of HMPs use has been reported in the UK [35]. Herbal medicinal products are bought over the counter, mostly self-prescribed [57] and often not disclosed to healthcare professionals [8, 9]. Reasons for the increasing use of HMPs include dissatisfaction with the effectiveness of conventional drugs, concerns about adverse effects of conventional drugs and misconception that HMPs are ‘natural’ and therefore safer, even when or particularly when used with prescription drugs [7]. Other reasons for the increased use of HMPs include desire to contribute to the treatment process and to improve general health, cultural and personal beliefs and better consultation experiences with herbal medicine practitioners when compared to conventional healthcare professionals [10].

Interactions between conventional drugs and HMPs can lead to adverse drug reactions (ADR), some with serious consequences [1114]. For example, ginkgo (Ginkgo biloba) when combined with anticoagulants can interfere with platelet functions. Although the majority of drug-drug interactions are known and preventable, little is known about the incidence and severity of HMP-drug interactions. The risk for ADRs increases with age [14, 15]. Considering that 16 % of the population of England and Wales are 65 years and older, this is an issue that needs closer attention [16]. Older people are more likely to live with multiple co-morbidities and experience medication-related problems because of delayed clearance of pharmacologically active compounds [1719]. Twenty per cent of over 70s take five or more prescribed medications [20, 21]; the number of medications increases the risk of an adverse drug event [22, 23]. Increased hospitalisation and prolonged hospital stays due to ADRs are also major clinical and economic concerns for all healthcare systems [24]. While there is a considerable body of knowledge on the use of herbal medicines by different age groups and for different conditions, there is limited evidence on the concurrent use of herbals with conventional medicines especially among older adults [25]. We define concurrent use as taking one or more HMPs in the same time period with a prescription medicine.

Aims

This systematic review aims to identify and synthesise the literature on prevalence, patterns, safety issues and other factors associated with concurrent prescription and HMP use in older adults.

Review questions

The review will seek to answer the following questions:
  1. a.

    What is the prevalence and pattern of the concurrent use of prescription drugs and herbal medicinal products (HMPs) among older adults?

     
  2. b.

    What patient and clinical characteristics are associated with the concurrent use of prescription drugs and HMPs?

     
  3. c.

    What are the range of prescription drugs and HMPs most concurrently used by older adults?

     
  4. d.

    What safety issues and other factors are associated with concurrent prescription drug and HMPs use in older adults?

     

Methods/design

Protocol and registration

The methods for this systematic review were developed according to recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement [26]. A populated PRISMA-P checklist is available as an Additional file 1 to this protocol. The protocol has been registered in the International Prospective Register of Systematic Reviews: PROSPERO 2014: CRD42014009091.

Eligibility criteria

We will include studies with participants who are ≥65 years, studies with a mean participant age of ≥65 years and studies from which standalone data for ≥65 years can be extracted. We will include studies assessing the concurrent use of HMPs or herbal dietary supplements with prescription medicines. Studies in which participants were on at least one prescription medicine and concurrently used one or more HMP will also be eligible.

Type of studies

We will include the following study designs:
  1. a.

    Quantitative study design: quantitative studies which may include cross-sectional studies to answer review questions on prevalence, pattern of use, range of prescription and HMPs and patient and clinical characteristics associated with concurrent use among older adults

     
  2. b.

    Qualitative study design: qualitative studies on satisfaction or dissatisfaction with HMPs and disclosure to healthcare professionals, as well as cost and resources expended on HMPs by older adults

     
  3. c.

    Mixed method studies: studies which have incorporated both quantitative and qualitative strands in their design

     
  4. d.

    Case reports of adverse events from the concurrent use of prescription drugs and HMPs among those aged 65 years and older

     

Studies assessing Chinese herbal medicine, Ayurvedia, Kampo, Siddha, Unani, homoeopathic remedies, non-herbal dietary supplements and vitamins will be excluded as they often contain products other than plants. Combination products, i.e. products that contain herbal as well as non-herbal (vitamins, minerals) ingredients will be excluded. Editorials, letters, commentaries and papers reporting in vitro experiments and animal studies will be excluded.

The primary outcomes of interest include prevalence and pattern of concurrent use, names and number of concurrently used medicines, adverse reactions or potential herb-drug interactions reported. Secondary outcomes of interests are the disclosure of HMPs use to healthcare professionals, satisfaction with HMPs and cost of HMPs, where reported.

Literature searches

We will search the following databases from inception to November 2015 using medical subject headings (MeSH) and text words related to ‘herbal medicine’, ‘prescription drugs’ and the scientific name and common names(s) of herbs most documented for concomitant use. Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO, Cochrane Library, Excerpta Medica dataBASE (EMBASE), MEDLINE (via PubMed), the Allied and Complementary Medicine Database (AMED), PsychINFO, Web of Science and Google Scholar. No restrictions will be placed on language of publication. The search strategy is available as an Additional file 2 to this protocol.

We will also search reference lists of all identified studies and review articles for relevant references not identified by the electronic search. Key authors and experts in the field identified from reference list of included studies will be contacted for information about ongoing or unpublished studies. Duplicate studies will be recorded and discarded. We will also perform lateral searching using the related citation function in PubMed and cited by function in Google scholar to capture all relevant articles.

Study selection process

Search results from all databases will be downloaded into Endnote and merged to remove duplicates. Two reviewers (Taofikat Agbabiaka (TA) and Barbara Wider (BW)) will scan all titles and abstracts for potential relevance. Any article for which there is uncertainty about relevance will be retained and the full text reviewed. Full text of all articles that may meet the eligibility criteria will be obtained and downloaded into Endnote.

Using a pre-designed eligibility checklist, two reviewers (TA and BW) will independently assess the full text of all obtained articles against the eligibility criteria and an eligibility code will be recorded. Studies that do not meet the inclusion criteria will be excluded and the reasons recorded. Any disagreements on eligibility will be resolved by discussion between two reviewers (TA and BW); if no consensus can be reached, a third reviewer (Claire Goodman (CG)) will be consulted.

Data extraction

Using a piloted data extraction form, one reviewer (TA) will extract the data from included studies and a second reviewer (BW) will validate the extracted data. Key data to be extracted will include the following:
  1. a.

    Publication details: author (s), year of publication, title of paper, journal and country in which study was conducted and funding information

     
  2. b.

    Study design: study type, recruitment method and data collection method(s)

     
  3. c.

    Study aims, outcomes and measurement of outcomes.

     
  4. d.

    Participants: demographic and socio-economic characteristics, number surveyed, or interviewed and previous medical diagnosis

     
  5. e.

    Name/description and number of HMPs and name and number of prescription drug(s)

     
  6. f.

    Details of safety issues: adverse reactions and interactions reported

     
  7. g.

    Disclosure, satisfaction and cost/resource

     
  8. h.

    Study limitations: response bias, selection bias, etc.

     

Any disagreements will be resolved by a third reviewer (CG) or by achieving a consensus through discussion. Studies that do not meet the inclusion criteria will be excluded and the reasons recorded.

Quality assessment

Two reviewers (TA and BW) will independently assess the methodological quality of each article that meets the inclusion criteria. Where appropriate, studies assessing prevalence will be assessed using the Joanna Briggs Institute (JBI) checklist for prevalence data [27]. Qualitative papers will be assessed for methodological rigour using the checklist developed by Critical Appraisal Skills Programme (CASP) [28].

Data synthesis

We will adopt the EPPI-Centre three stages approach to mixed method research synthesis [29]. A first synthesis will aim to address prevalence, pattern of use and patient characteristics associated with the concurrent use of herbal medicinal products and prescription medicines. A second synthesis of qualitative research will address the fourth review question, i.e. safety issues and other factors such as disclosure, satisfaction and cost/resources. We do not anticipate many qualitative research papers; therefore, synthesis will depend on available data. We will use thematic synthesis to identify key themes, commonalities, and why HMPs are thought to be helpful or necessary [30]. Findings from both quantitative and qualitative stages will be summarised in a narrative account that addresses the review questions to provide a better understanding of concurrent medicine use among older adults.

Results of the search and study selection process will be presented in a flow chart [31]. Relevant data extracted from eligible studies will be presented as an evidence table. We will describe the study characteristics including details of study types, population characteristics and outcomes. We will provide a narrative synthesis of the summary of prevalence, patterns and safety issues from concurrent prescription and HMPs use in older adults. Where appropriate we will present data in tables and graphics. We will provide a detailed discussion of the limitations of the included studies and their implications on the findings. We will identify gaps in knowledge and provide suggestions for future research.

Discussion

Failure to review and manage the concurrent use of prescription and herbal medicines in older adults is a considerable patient safety risk. Excessive and inappropriate medicine use is common among older adults [32, 33], and concurrent use with HMPs further complicates the problem.

This review is a significant addition to knowledge due to the paucity of evidence on the concurrent use of prescription drugs and HMPs in older adults. There is no up-to-date review on concurrent prescription and herbal medicine use among UK older adults; the only previous related study [34] is over a decade old. The review will provide healthcare professionals with up-to-date knowledge on the prevalence and factors associated with concurrent medication use among this population. It will also provide important baseline information for future intervention research.

Dissemination

Findings from this systematic review will form part of TA’s doctoral thesis. The review will be prepared following PRISMA reporting standards for submission to a peer-reviewed journal with focus on care of older adults or drug safety and presented at conferences.

Abbreviations

ADR: 

adverse drug reaction

AMED: 

Allied and Complementary Medicine Database

BW: 

Barbara Wider

CASP: 

Critical Appraisal Skills Programme

CG: 

Claire Goodman

CINAHL: 

Cumulative Index to Nursing and Allied Health Literature

EMBASE: 

Excerpta Medica dataBASE

HMP: 

herbal medicinal product

MeSH: 

medical subject heading

PRISMA-P: 

Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols

PROSPERO: 

International Prospective Register of Systematic Reviews

TA: 

Taofikat Agbabiaka

Declarations

Acknowledgements

We thank Jayne Griffiths for conducting initial literature search and Frances Bunn for reviewing drafts of the protocol.

Funding

The authors declare that no external funding was received for this study.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Centre for Research in Primary and Community Care (CRIPACC), University of Hertfordshire
(2)
Patient Safety Domain, Nursing Directorate, NHS England
(3)
Institute of Health Research, University of Exeter Medical School

References

  1. Shaw D, Graeme L, Pierre D, Elizabeth W, Kelvin C. Pharmacovigilance of herbal medicine. J Ethnopharmacol. 2012;140(3):513–8.View ArticlePubMedGoogle Scholar
  2. Commission of the European Communities. Amended proposal for a directive of the European parliament and of the council amending the directive 2001/83/EC as regards traditional herbal medicinal products. Brussels: European Commission; 2003.Google Scholar
  3. Hunt KJ, Coelho HF, Wider B, Perry R, Hung S, Terry R, et al. Complementary and alternative medicine use in England: results from a national survey. Int J Clin Pract. 2010;64(11):1496–502.View ArticlePubMedGoogle Scholar
  4. Thomas KJ, Nicholl JP, Coleman P. Use and expenditure on complementary medicine in England: a population based survey. Complement Ther Med. 2001;9(1):2–11.View ArticlePubMedGoogle Scholar
  5. MHRA, Ipsos MORI. Public perception of herbal medicines. London: MHRA; 2008.Google Scholar
  6. Barnes J. Pharmacovigilance of herbal medicines. Drug Saf. 2003;26(12):829–51.View ArticlePubMedGoogle Scholar
  7. Lynch N, Berry D. Differences in perceived risks and benefits of herbal, over-the-counter conventional, and prescribed conventional, medicines, and the implications of this for the safe and effective use of herbal products. Complement Ther Med. 2007;15(2):84–91. doi:10.1016/j.ctim.2006.06.007.View ArticlePubMedGoogle Scholar
  8. Walji R, Boon H, Barnes J, Welsh S, Austin Z, Baker GR. Reporting natural health product related adverse drug reactions: is it the pharmacist’s responsibility? Int J Pharm Pract. 2011;19(6):383–91.View ArticlePubMedGoogle Scholar
  9. Barnes J, Mills SY, Abbot NC, Willoughby M, Ernst E. Different standards for reporting ADRs to herbal remedies and conventional OTC medicines: face‐to‐face interviews with 515 users of herbal remedies. Br J Clin Pharmacol. 1998;45(5):496–500.View ArticlePubMedPubMed CentralGoogle Scholar
  10. Ernst E, White A. The BBC survey of complementary medicine use in the UK. Complement Ther Med. 2000;8(1):32–6.View ArticlePubMedGoogle Scholar
  11. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61(15):2163–75.View ArticlePubMedGoogle Scholar
  12. Williamson EM. Synergy and other interactions in phytomedicines. Phytomedicine: Int J Phycol Phycochem. 2001;8(5):401–9.View ArticleGoogle Scholar
  13. Williamson EM, Driver S, Baxter K, editors. Stockley’s herbal medicines interactions. 2nd ed. London: Pharmaceutical Press; 2013.Google Scholar
  14. Fugh-Berman A. Herb-drug interactions. Lancet. 2000;355(9198):134–8.View ArticlePubMedGoogle Scholar
  15. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS ONE. 2009;4(2), e4439.View ArticlePubMedPubMed CentralGoogle Scholar
  16. Office for National Statistics. What does the 2011 Census tell us about the “oldest old” living in England & Wales? Office for National Statistics. 2013. http://www.ons.gov.uk/ons/publications/index.html. Accessed 3rd October 2015.
  17. Salmond S. Polypharmacy and phytotherapy: issues of herb/drug interactions in the elderly. Aust J Med Herbalism. 2002;14(1):9.Google Scholar
  18. Vacas Rodilla E, Castella Daga I, Sanchez Giralt M, Pujol Algue A, Pallares Comalada MC, Balague CM. Self-medication and the elderly. The reality of the home medicine cabinet. Atencion primaria/Sociedad Espanola de Medicina de Familia y Comunitaria. 2009;41(5):269–74.View ArticlePubMedGoogle Scholar
  19. Mangoni AA, Jackson SH. Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57(1):6–14.View ArticlePubMedPubMed CentralGoogle Scholar
  20. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287(3):337–44.View ArticlePubMedGoogle Scholar
  21. Rollason V, Vogt N. Reduction of polypharmacy in the elderly. Drugs Aging. 2003;20(11):817–32.View ArticlePubMedGoogle Scholar
  22. Eichhorn T, Greten HJ, Efferth T. Self-medication with nutritional supplements and herbal over-the-counter products. Nat Prod Bioprospect. 2011;1:9.View ArticleGoogle Scholar
  23. Heuberger R. Polypharmacy and food–drug interactions among older persons: a review. J Nutr Gerontol Geriatr. 2012;31(4):325–403.View ArticlePubMedGoogle Scholar
  24. Sultana J, Cutroneo P, Trifirò G. Clinical and economic burden of adverse drug reactions. J Pharmacol Pharmacother. 2013;4(Suppl1):S73.View ArticlePubMedPubMed CentralGoogle Scholar
  25. de Souza Silva JE, Souza CAS, da Silva TB, Gomes IA, de Carvalho BG, de Souza Araújo AA, et al. Use of herbal medicines by elderly patients: a systematic review. Arch Gerontol Geriatr. 2014;59(2):227–33.View ArticlePubMedGoogle Scholar
  26. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349:g7647.View ArticlePubMedGoogle Scholar
  27. Institute TJB. Reviewers manual. 2014th ed. South Australia: The Joanna Briggs Institute, The University of Adelaide; 2014.Google Scholar
  28. Critical Appraisal Skills Programme (CASP). Qualitative research checklist. CASP UK, Oxford. 2013. http://www.casp-uk.net/#!casp-tools-checklists/c18f8. Accessed 16th October 2015.
  29. Josephine Kavanagh FC, Angela Harden and James Thomas. Mixed methods synthesis: a worked example. In: Hannes K, Lockwood C, editors. Synthesizing qualitative research: choosing the right approach. John Wiley & Sons; 2011. p. 113-36.
  30. Thomas J, Harden A. Methods for the thematic synthesis of qualitative research in systematic reviews. BMC Med Res Methodol. 2008;8(1):1.View ArticleGoogle Scholar
  31. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.View ArticlePubMedGoogle Scholar
  32. Qato DM, Alexander GC, Conti RM, Johnson M, Schumm P, Lindau ST. Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States. JAMA. 2008;300:2867–78.View ArticlePubMedPubMed CentralGoogle Scholar
  33. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57–65.View ArticlePubMedGoogle Scholar
  34. Canter PH, Ernst E. Herbal supplement use by persons aged over 50 years in Britain: frequently used herbs, concomitant use of herbs, nutritional supplements and prescription drugs, rate of informing doctors and potential for negative interactions. Drugs Aging. 2004;21(9):597–605.View ArticlePubMedGoogle Scholar

Copyright

© Agbabiaka et al. 2016

Advertisement