Skip to main content
SpringerLink
Log in

Study of Natural Products Adverse Reactions (SONAR) in Adults with Mental Health Conditions: A Cross-Sectional Study

  • Original Research Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Introduction

Mental illness is a leading cause of non-fatal disease burden worldwide. Natural health products (NHPs) are sought by patients with mental health conditions as a safer and more ‘natural’ option than conventional pharmacotherapy; however, the possible adverse events (AE) and interactions between NHPs and prescription medicines are not fully known.

Objectives

The aim of this study was to determine (i) the prevalence of adult patients with mental health conditions taking prescription medications only, NHPs only, NHPs and prescription medications concurrently, or neither, (ii) which prescription medications and NHPs are most commonly used, (iii) AEs (serious and non-serious) experienced in the last 30 days for each product use group.

Methods

Mental health clinics in Alberta and Ontario, Canada, were included in an active surveillance study investigating NHP–drug interactions. On their first clinic visit, adult mental health patients were provided with a form inquiring about prescription drug use, NHP use, and any undesirable health events experienced in the last month. Healthcare professionals were also asked to report AEs.

Results

A total of 3079 patients were screened at 11 mental health clinics in Alberta and Ontario. In total, 620 AEs were reported in 447 patients (14.9%). The majority of adverse events were seen in patients using both NHPs and prescription medicines (58.8%), followed by patients taking only prescription medicines (37.1%), NHPs only (3.4%) and neither (0.67%). Combining NHPs and prescription medications increases the likelihood of experiencing AEs (OR 2.1; p < 0.001; 95% CI 1.7–2.6).

Conclusions

Adult patients with mental health conditions who are taking both prescription medications and NHPs are more likely to report an adverse event than patients taking prescription drugs or NHPs alone. Polypharmacy increases the likelihood of an adverse event. Active surveillance is feasible and could contribute to enhanced pharmacovigilance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Reid I. Natural health product tracking survey—2010 final report. Heal Canada [Internet]. 2011;73. https://books.google.ca/books/about/Natural_Health_Product_Tracking_Survey_2.html?id=wiv8MgEACAAJ&redir_esc=y.

  2. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382:1575–86.

    Article  Google Scholar 

  3. Mental Health Commission of Canada. Making the case for investing in mental health in Canada. 2010;30. https://www.mentalhealthcommission.ca/sites/default/files/2016-06/Investing_in_Mental_Health_FINAL_Version_ENG.pdf

  4. Government of Canada. Natural and non-prescription health products [Internet]. 2015. https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription.html. Cited 13 May 2018

  5. Ratnasingham S, Cairney J, Manson H, Rehm J, Lin E, Kurdyak P. The burden of mental illness and addiction in Ontario. Can J Psychiatry. 2013;58:529–37.

    Article  Google Scholar 

  6. Murray CJL, Lopez AD. Measuring the global burden of disease. N Engl J Med. 2013;369:448–57. https://doi.org/10.1056/NEJMra1201534.

    Article  CAS  PubMed  Google Scholar 

  7. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21:655–79.

    Article  CAS  Google Scholar 

  8. Beringer A, Vaillancourt R, Villarreal G, Vadeboncoeur C. The use of natural health products by paediatric patients in respite care. Paediatr Child Health. 2015;20:23–9.

    Article  Google Scholar 

  9. Jordan SA, Cunningham DG, Marles RJ. Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxicol Appl Pharmacol. 2010;43:198–216.

    Article  Google Scholar 

  10. Davison KM, Kaplan BJ. Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events. BMC Complement Altern Med. 2013;13:1.

    Article  Google Scholar 

  11. Morgan TK, Williamson M, Pirotta M, Stewart K, Myers SP, Barnes J. A national census of medicines use: a 24-hour snapshot of Australians aged 50 years and older. Med J Aust. 2012;190:50–3.

    Article  Google Scholar 

  12. Necyk C, Khamba B, Chue P, Urichuk L, Snaterse M, Vohra S. Study of natural health product-drug adverse reactions (S.O.N.A.R.) in patients seeking mental health services. Curr Med Res Opin. 2016;32:1335–43.

    Article  Google Scholar 

  13. Hu XH, Bull SA, Hunkeler EM, Ming E, Lee JY, Fireman B, et al. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry United States. 2004;65:959–65.

    Article  CAS  Google Scholar 

  14. Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults meta-analysis of drug company data from placebo controlled randomised controlled trials submitted to the MHRA’s safety review. BMJ Engl. 2005;330:385.

    Article  CAS  Google Scholar 

  15. Lader M, Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care. CNS drugs. New Zealand. 2009;23:19–34.

    CAS  Google Scholar 

  16. Hall WD, Lucke J. How have the selective serotonin reuptake inhibitor antidepressants affected suicide mortality? Aust N Z J Psychiatry Engl. 2006;40:941–50.

    Article  Google Scholar 

  17. Cascade E, Kalali AH, Kennedy SH. Real-world data on SSRI antidepressant side effects. Psychiatry Edgmont US. 2009;6:16–8.

    Google Scholar 

  18. Gartlehner G, Thieda P, Hansen RA, Gaynes BN, Deveaugh-Geiss A, Krebs EE, et al. Comparative risk for harms of second-generation antidepressants: a systematic review and meta-analysis. Drug Saf N Zeal. 2008;31:851–65.

    Article  CAS  Google Scholar 

  19. Cheung R, O’Donnell S, Madi N, Goldner EM. Factors associated with delayed diagnosis of mood and/or anxiety disorders. Heal Promot Chronic Dis Prev Canada. 2017;37:137–48.

    Article  Google Scholar 

  20. Borrelli F, Izzo AA. Herb–drug interactions with St John’s Wort (Hypericum perforatum): an update on clinical observations. Am Assoc Pharm Sci. 2009;11.

  21. Bunting BP, Murphy SD, O’Neill SM, Ferry FR. Lifetime prevalence of mental health disorders and delay in treatment following initial onset: evidence from the Northern Ireland study of health and stress. Psychol Med Engl. 2012;42:1727–39.

    Article  CAS  Google Scholar 

  22. Kessler RC, Soukup J, Davis RB, Foster DF, Wilkey SA, Van Rompay MI, et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry US. 2001;158:289–94.

    Article  CAS  Google Scholar 

  23. Howland RH. Dietary supplement drug therapies for depression. J Psychosoc Nurs Ment Health Serv US. 2012;50:13–6.

    Google Scholar 

  24. FDA 101: Regulating biological products [Internet]. U.S. Food Drug. 2018. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048341.htm. Cited 5 Feb 2019

  25. Votova K, Blais R, Penning MJ, Maclure MK. Polypharmacy meets polyherbacy: pharmaceutical, over-the-counter, and natural health product use among Canadian adults. Can J Public Health Switz. 2013;104:e222–8.

    Article  Google Scholar 

  26. Government of Canada. About natural health products [Internet]. 2016. https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/regulation/about-products.html. Cited 6 Oct 2020

  27. Guthrie B, Makubate B, Hernandezantiago V, Dreischulte T. The rising tide of polypharmacy and drug–drug interactions: population database analysis. BMC Med Engl. 2015;13:74.

    Article  Google Scholar 

  28. Sparks E, Zorzela L, Necyk C, Khamba B, Urichuk L, Barnes J, et al. Study of Natural products Adverse Reactions (SONAR) in children seen in mental health clinics: a cross-sectional study. BMJ Paediatr Open. 2020;4:674.

    Article  Google Scholar 

  29. Jong MC, van Vliet M, Huttenhuis S, van der Veer D, van den Heijkant S. Attitudes toward integrative paediatrics: a national survey among youth health are physicians in the Netherlands. BMC Complement Altern Med. 2012;12:1–8.

    Article  Google Scholar 

  30. Alvarez-Requejo A, Carvajal A, Begaud B, Moride Y, Vega T, Arias LH. Under-reporting of adverse drug reactions Estimate based on a spontaneous reporting scheme and a sentinel system. Eur J Clin Pharmacol Ger. 1998;54:483–8.

    Article  CAS  Google Scholar 

  31. Vohra S, Boon H, Cvijovic K. Active surveillance in community pharmacies: qualitative and quantitative data of adverse reaction case reports. Health Canada; 2009.

  32. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4:1623–7.

    Google Scholar 

  33. Health Canada. Guidance document for industry—reporting adverse reactions to marketed health products. 2018. https://www.canada.ca/en/health-canada/services/drugs-health-products/reports-publications/medeffect-canada/reporting-adverse-reactions-marketed-health-products-guidance-industry.html

  34. NIH. CTCAE common terminology criteria adverse events. Natl Inst Heal Natl Cancer Inst [Internet]. 2017;0–71. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_ Reference_8.5x11.pdf%0A, http://www.uptodate.com/contents/common-terminology-criteria-for-adverse-events.

  35. Uppsala Monitoring Centre. Glossary of pharmacovigilance terms. 2018. https://www.who-umc.org/global-pharmacovigilance/global-pharmacovigilance/glossary/. Cited 1 June 2018.

  36. Zorzela L, Mior S, Boon H, Gross A, Yager J, Carter R, et al. Tool to assess causality of direct and indirect adverse events associated with therapeutic interventions. Curr Med Res Opin Engl. 2018;34:407–14.

    Article  Google Scholar 

  37. Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41:674–80.

    Article  Google Scholar 

  38. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45. https://doi.org/10.1038/clpt.1981.154.

    Article  CAS  PubMed  Google Scholar 

  39. Uppsala drug monitoring centre. WHO adverse drug event causality assessment criteria. 2011. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf

  40. Vohra S, Cvijovic K, Boon H, Foster BC, Jaeger W, LeGatt D, et al. Study of natural health product adverse reactions (SONAR): Active surveillance of adverse events following concurrent natural health product and prescription drug use in community pharmacies. PLoS One. 2012;7. Available from: https://pubmed.ncbi.nlm.nih.gov/23028841/.

  41. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap)—a metadata driven methodology and workflow process for providing translational research informatict support. J Biomed Inform. 2009;42:377–81.

    Article  Google Scholar 

  42. StataCorp. Stata Statistical Software. College Station, TX; 2015.

  43. Jyrkka J, Enlund H, Korhonen MJ, Sulkava R, Hartikainen S. Polypharmacy status as an indicator of mortality in an elderly population. Drugs Aging N Zeal. 2009;26:1039–48.

    Article  Google Scholar 

  44. Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med US. 2015;175:827–34.

    Article  Google Scholar 

  45. Nobili A, Licata G, Salerno F, Pasina L, Tettamanti M, Franchi C, et al. Polypharmacy, length of hospital stay, and in-hospital mortality among elderly patients in internal medicine wards. The REPOSI study. Eur J Clin Pharmacol Ger. 2011;67:507–19.

    Article  Google Scholar 

  46. Gomez C, Vega-Quiroga S, Bermejo-Pareja F, Medrano MJ, Louis ED, Benito-Leon J. Polypharmacy in the elderly: a marker of increased risk of mortality in a population-based prospective study (NEDICES). Gerontology Switzerland. 2015;61:301–9.

    Article  Google Scholar 

  47. Bourgeois FT, Shannon MW, Valim C, Mandl KD. Adverse drug events in the outpatient setting: an 11-year national analysis. Pharmacoepidemiol Drug Saf. 2010;19:901–10.

    Article  Google Scholar 

  48. Levine MAH, Xu S, Gaebel K, Brazier N, Bedard M, Brazil K, et al. Self-reported use of natural health products: a cross-sectional telephone survey in older Ontarians. Am J Geriatr Pharmacother US. 2009;7:383–92.

    Article  Google Scholar 

  49. Alherbish A, Charrois TL, Ackman ML, Tsuyuki RT, Ezekowitz JA. The prevalence of natural health product use in patients with acute cardiovascular disease. PLoS One. 2011;6.

  50. Geil P, Shane-McWhorter L. Dietary supplements in the management of diabetes: potential risks and benefits. J Am Diet Assoc US. 2008;108:S59-65.

    Article  Google Scholar 

  51. Necyk C, Khamba B, Chue P, Urichuk L, Snaterse M, Vohra S. Study of natural health product-drug adverse reactions (SONAR) in patients seeking mental health services. Curr Med Res Opin Engl. 2016;32:1335–43.

    Article  Google Scholar 

  52. Wiktorowicz M, Lexchin J, Moscou K, Silversides A, Eggertson L. Keeping an eye on prescription drugs, keeping Canadians safe. Active Monitoring Systems for Drug Safety and Effectiveness in Canada and Internationally [Internet]. Heal. Counc. Canada. Toronto; 2010. Available from: https://www.healthcouncilcanada.ca.

  53. Shojania KG, Duncan BW, McDonald KM, Wachter RM, Markowitz AJ. Making health care safer: a critical analysis of patient safety practices. Evid Rep Technol Assess Summ US. 2001;i–x:1–668.

    Google Scholar 

  54. Zimmerman M, Grenier D, Levitt M. Does active surveillance of serious and life-threatening adverse drug reactions improve reporting? Paediatr Child Health (Oxf). 2011;16:532–4.

    Article  Google Scholar 

  55. Canadian Safety Institute. Best possible medication history [Internet]. 2016. http://www.patientsafetyinstitute.ca/en/Topic/Pages/Best-Possible-Medication-History.aspx. Cited 2 Aug 2018

  56. Hohl CM, Small SS, Peddie D, Badke K, Bailey C, Balka E. Why clinicians don’t report adverse drug events: qualitative study. JMIR Public Heal Surveill. 2018;4:21.

    Article  Google Scholar 

  57. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ Engl. 2004;329:15–9.

    Article  Google Scholar 

  58. Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol US. 2012;65:989–95.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank to all members of the SONAR steering committee for their contributions on the development of the SONAR projects. A special thank you to Dr Heather Boon for her ongoing active collaboration in this work.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 4-584 Edmonton Clinic Health Academy (ECHA), 11405-87 Ave NW, Edmonton, AB, T6G 1C9, Canada

    Liliane Zorzela & Sunita Vohra

  2. Naturopathic Medicine, Bastyr University California-San Diego Campus, San Diego, USA

    Baljit Khamba

  3. Temerty Faculty of Medicine, University of Toronto, Toronto, Canada

    Emma Sparks

  4. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada

    Candace Necyk

  5. Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

    Liana Urichuk, Pierre Chue & Sunita Vohra

  6. S.T.A.R.T. Clinic (Stress, Trauma, Anxiety, Rehabilitation and Treatment) for Mood and Anxiety Disorders, Northern School of Medicine (NOSM), Thunder Bay, Canada

    Martin A. Katzman

  7. Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada

    David Koczerginski

  8. School of Pharmacy, University of Auckland, Auckland, New Zealand

    Joanne Barnes

Authors
  1. Liliane Zorzela
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Baljit Khamba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emma Sparks
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Candace Necyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liana Urichuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Martin A. Katzman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David Koczerginski
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pierre Chue
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joanne Barnes
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sunita Vohra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sunita Vohra.

Ethics declarations

Funding

This study received financial support from two Grants agencies in a partnership fund, Canadian Institute for Health Research (CIHR) (RES0021177) and Alberta Innovates Health Solutions (RES0025318), both from Edmonton, Alberta, Canada. The Grant agencies had no interventions or participation in the study or manuscript development.

Conflict of interest

Martin Katzman is a member on the advisory board for the following drug companies: Abbvie, Eisai, Empower Pharma, Janssen, Otsuka, Pfizer, Purdue, Santé Cannabis, Shire, Takeda and Tilray. He has also received honoraria from Allergan, Jansen, Lundback, Otsuka, Pfizer, Purdue, Shire, Takeda and Tilray, a research grant from Pfizer, and is involved in a clinical trial with Lundbeck. Joanne Barnes reports non‐financial support from Achieve Life Sciences during a clinical trial of cytisine. She also reports personal fees from New Zealand Ministry of Health Natural Health Products (NHPs) Regulations Subcommittee on the Permitted Substances List (member of subcommittee 2016–17), non‐financial support from Uppsala Monitoring Centre, Sweden (who manages the technical and scientific aspects of the WHO Programme for International Drug Monitoring); honorary consultant and herbal safety signal reviewer (2004–current), outside the submitted work. These conflicts are not related to this paper. All other authors have no conflicts of interest to disclose.

Availability of data and material

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Consent to publish and participate

As is consistent with other SONAR studies, the initial screening questions are a part of ideal clinical care (e.g., best possible medication history), so HREB approval was granted making additional research consent unnecessary.

Ethics approval

This study was approved by the Human Research Ethics Board at the University of Alberta (MS21 Pro00025387). The STROBE guideline was used to report this study.

Code availability

Not applicable.

Author contributions

Contribution statement: LZ, BK, CN, ES collect the study data and helped on the development of the manuscript, LU, PC, DK, MK, JB and SV developed the study methods and helped drafting the manuscript. All authors read and approved the final version.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 287 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zorzela, L., Khamba, B., Sparks, E. et al. Study of Natural Products Adverse Reactions (SONAR) in Adults with Mental Health Conditions: A Cross-Sectional Study. Drug Saf 44, 999–1006 (2021). https://doi.org/10.1007/s40264-021-01092-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40264-021-01092-w

Search

Navigation