International Journal of Clinical Pharmacy

, Volume 40, Issue 5, pp 1234–1241 | Cite as

Unintentional and intentional non-adherence to immunosuppressive medications in renal transplant recipients

  • Konstadina GrivaEmail author
  • Hui Ling Michelle Neo
  • Anantharaman Vathsala
Research Article


Background Non-adherence to immunosuppressive medications following renal transplantation is a risk factor for rejection and graft loss. Despite the dire consequences, adherence lapses, both unintentional and intentional, are common and poorly understood. Objective The present study sets to compare the rates and determinants of unintentional, intentional and overall self-reported non-adherence. Setting Outpatient clinic at the National University Centre for Organ Transplantation, Singapore. Method This was a cross-sectional survey administered to N = 152 renal transplant recipients. Main outcome measure They completed the Transplant Effects Questionnaire, Beliefs about Medications Questionnaire, Multidimensional Scale of Perceived Social Support, the Depression, Anxiety and Stress Scale, and the Medication Adherence Report Scale. Clinical and laboratory information were also assessed. Results The prevalence rates for overall, unintentional, and intentional self-reported non-adherence were 19.7, 47.4, and 15.1% respectively. Unintentional non-adherence was predicted by engagement in formal work, a primary diagnosis of autoimmune nephritis, and being a recipient of a living-donor renal transplant (i.e. stable characteristics). In contrast, intentional non-adherence was predicted by co-morbid burden and patients’ evaluation of the side effects of their medications. Overall non-adherence was predicted by a deliberate decision-making process involving the weighing of the costs of using immunosuppressive drugs against their perceived benefits. Conclusion The survey highlighted the importance of making a distinction between unintentional and intentional non-adherence in renal transplant recipients, and suggested that modifiable factors may be targeted in different ways in interventions to increase adherence.


Immunosuppressive medications Intentional Non-adherence Renal transplant Self-reported Singapore Unintentional 



The authors appreciate the assistance of Ms. Vanessa Lee and Ms. Priscilla Loh in data collection, and Ms. Tanusya Murali and Ms. Amy Lim for administrative support.


No funding was received for this study.

Conflicts of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Laupacis A, Keown P, Pus N, et al. A study of the quality of life and cost-utility of renal transplantation. Kidney Int. 1996;50:235–42.CrossRefGoogle Scholar
  2. 2.
    Loubeau PR, Loubeau JM, Jantzen R. The economics of kidney transplantation versus hemodialysis. Prog Transpl. 2001;11:291–7.CrossRefGoogle Scholar
  3. 3.
    Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725–30.CrossRefGoogle Scholar
  4. 4.
    Morris PJ, Knechtle SJ. Kidney transplantation: principles and practice. Philadelphia: Sauders; 2013.Google Scholar
  5. 5.
    Butler JA, Roderick P, Mullee M, Mason JC, Peveler RC. Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Transplantation. 2001;77:769–76.CrossRefGoogle Scholar
  6. 6.
    Denhaerynck K, Dobbels F, Cleemput I, et al. Prevalence, consequences, and determinants of nonadherence in adult renal transplant patients: a literature review. Transplant Int. 2005;18:1121–33.CrossRefGoogle Scholar
  7. 7.
    Chisholm M, Vollenweider LJ, Mulloy LL, et al. Renal transplant patient compliance with free immunosuppressive medications. Transplantation. 2000;70:1240–4.CrossRefGoogle Scholar
  8. 8.
    Ghods AJ, Nasrollahzadeh D, Argani H. Risk factors for noncompliance to immunosuppressive medications in renal transplant recipients. Transplant Proc. 2003;35:2609–11.CrossRefGoogle Scholar
  9. 9.
    Butler J, Peveler R, Roderick P, Horne R, Mason J. Measuring compliance with drug regimens after renal transplantation: comparison of self-report and clinician rating with electronic monitoring. Transplantation. 2004;77:786–9.CrossRefGoogle Scholar
  10. 10.
    Achille MA, Ouellette A, Fournier S, Vachon M, Hébert MJ. Impact of stress, distress and feelings of indebtedness on adherence to immunosuppressants following kidney transplantation. Clin Transplant. 2006;20:301–6.CrossRefGoogle Scholar
  11. 11.
    Orr A, Orr D, Willis S, Holmes M, Britton P. Patient perceptions of factors influencing adherence to medication following kidney transplant. Psychol Health Med. 2007;12:509–17.CrossRefGoogle Scholar
  12. 12.
    Prihodova L, Nagyova I, Rosenberger J, et al. Adherence in patients in the first year after kidney transplantation and its impact on graft loss and mortality: a cross-sectional and prospective study. J Adv Nurs. 2014;70:2871–83.CrossRefGoogle Scholar
  13. 13.
    Vlaminck H, Maes B, Evers G, et al. Prospective study on late consequences of subclinical non-compliance with immunosuppressive therapy in renal transplant patients. Am J Transplant. 2004;4:1509–13.CrossRefGoogle Scholar
  14. 14.
    Horne R, Weinman J. Patients’ beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J Psychosom Res. 1999;47:555–67.CrossRefGoogle Scholar
  15. 15.
    Horne R, Parham R, Driscoll R, Robinson A. Patients’ attitudes to medicines and adherence to maintenance treatment in inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:837–44.CrossRefGoogle Scholar
  16. 16.
    Horne R, Chapman S, Parham R, Freemantle N, Forbes A, Cooper V. Understanding patients’ adherence-related beliefs about medicines prescribed for long-term conditions: a meta-analytic review of the necessity-concerns framework. PLoS ONE. 2013;8:e80633.CrossRefGoogle Scholar
  17. 17.
    World Health Organization. Adherence to long-term therapies: evidence for action (internet). 2003. Accessed 4 Nov 2017.
  18. 18.
    Clifford S, Barber N, Horne R. Understanding different beliefs held by adherers, unintentional nonadherers, and intentional nonadherers: application of the necessity-concerns framework. J Psychosom Res. 2008;64:41–6.CrossRefGoogle Scholar
  19. 19.
    Lehane E, McCarthy G. Intentional and unintentional medication non-adherence: a comprehensive framework for clinical research and practice? A discussion paper. Int J Nurs Stud. 2007;44:1468–77.CrossRefGoogle Scholar
  20. 20.
    Wroe AL. Intentional and unintentional nonadherence: a study of decision making. Int J Behav Med. 2002;25:355–72.CrossRefGoogle Scholar
  21. 21.
    Griva K, Davenport A, Harrison M, Newman SP. Non-adherence to immunosuppressive medications in kidney transplantation: intent vs. forgetfulness and clinical markers of medication intake. Ann Behav Med. 2012;44:85–93.CrossRefGoogle Scholar
  22. 22.
    Iihara N, Kurosaki Y, Miyoshi C, Takabatake K, Morita S, Hori K. Comparison of individual perceptions of medication costs and benefits between intentional and unintentional medication non-adherence among Japanese patients. Patient Educ Couns. 2008;70:292–9.CrossRefGoogle Scholar
  23. 23.
    Lim MK, Sadarangani P, Chan HL, Heng JY. Complementary and alternative medicine use in multiracial Singapore. Complement Ther Med. 2005;13:16–24.CrossRefGoogle Scholar
  24. 24.
    Kim U. Asian collectivism: an indigenous perspective. In: Kao HSR, Sinha D, editors. Asian perspectives on psychology. Cross-cultural research and methodology series. Thousand Oaks: Sage Publications; 1997. p. 147–63 (ISBN 0803992939).Google Scholar
  25. 25.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis Manag. 1987;40:373–83.CrossRefGoogle Scholar
  26. 26.
    Jassal SV, Schaubel DE, Fenton SS. Baseline comorbidity in kidney transplant recipients: a comparison of comorbidity indices. Am J Kidney Dis. 2005;46:136–42.CrossRefGoogle Scholar
  27. 27.
    Ziegelmann JP, Griva K, Hankins M, et al. The Transplant Effects Questionnaire (TxEQ): the development of a questionnaire for assessing the multidimensional outcome of organ transplantation. Br J Health Psychol. 2002;7:393–408.CrossRefGoogle Scholar
  28. 28.
    Calia R, Lai C, Aceto P, et al. Effects of switching from twice-daily to once-daily tacrolimus formulation on quality of life, anxiety, and transplant benefit perception after kidney transplantation. Transplant Proc. 2011;43:1020–3.CrossRefGoogle Scholar
  29. 29.
    Griva K, Ziegelmann JP, Thompson D, et al. Quality of life and emotional responses in cadaver and living related renal transplant recipients. Nephrol Dial Transplant. 2002;17:2204–11.CrossRefGoogle Scholar
  30. 30.
    Horne R, Weinman J, Hankins M. The beliefs about medicines questionnaire: the development and evaluation of a new method for assessing the cognitive representation of medication. Psychol Health. 1999;14:1–24.CrossRefGoogle Scholar
  31. 31.
    Zimet GD, Dahlem NW, Zimet SG, Farley GK. The multidimensional sclae of perceived social support. J Pers Assess. 1998;52:30–41.CrossRefGoogle Scholar
  32. 32.
    Lovibond S, Lovibond P. Manual for the depression anxiety stress scales. 2nd ed. Sydney: Psychology Foundation; 1995 (ISBN 7334-1423-0).Google Scholar
  33. 33.
    Antony MM, Bieling PJ, Cox BJ, Enns MW, Swinson RP. Psychometric properties of the 42-item and 21-item versions of the depression anxiety stress scales in clinical groups and a community sample. Psychol Assess. 1998;10:176–81.CrossRefGoogle Scholar
  34. 34.
    Covic T, Cumming SR, Pallant JF, et al. Depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a comparison of the depression, anxiety and stress scale (DASS) and the hospital, anxiety and depression scale (HADS). BMC Psychiatry. 2012;12:2–10.CrossRefGoogle Scholar
  35. 35.
    Mitchell MC, Burns NR, Dorstyn DS. Screening for depression and anxiety in spinal cord injury with DASS-21. Spinal Chord. 2008;46:547–51.CrossRefGoogle Scholar
  36. 36.
    Horne R, Weinman J. Self-regulation and self-management in asthma: exploring the role of illness perceptions and treatment beliefs in explaining non-adherence to preventer medication. Psychol Health. 2002;17:17–32.CrossRefGoogle Scholar
  37. 37.
    Molloy GJ, Messerli-Bürgy N, Hutton G, Wikman A, Perkins-Porras L, Steptoe A. Intentional and unintentional non-adherence to medications following an acute coronary syndrome: a longitudinal study. J Psychosom Res. 2014;76:430–2.CrossRefGoogle Scholar
  38. 38.
    Hatah E, Lim KP, Ali AM, Shah NM, Islahudin F. The influence of cultural and religious orientations on social support and its potential impact on medication adherence. Patient Prefer Adherence. 2015;9:589–96.CrossRefGoogle Scholar
  39. 39.
    Daleboudt GM, Broadbent E, McQueen F, Kaptein AA. Intentional and unintentional treatment nonadherence in patients with systemic lupus erythematosus. Arthritis Care Res. 2011;63:342–50.Google Scholar
  40. 40.
    Gadkari AS, McHorney CA. Unintentional non-adherence to chronic prescription medications: how unintentional is it really? BMC Health Serv Res. 2012;12:1–12.CrossRefGoogle Scholar
  41. 41.
    Wray J, Waters S, Radley-Smith R, Sensky T. Adherence in adolescents and young adults following heart or heart-lung transplantation. Pediatr Transplant. 2006;10:694–700.CrossRefGoogle Scholar
  42. 42.
    Vathsala A. Renal transplantation in Singapore. Ann Acad Med Singapore. 2009;38:291–9.PubMedGoogle Scholar
  43. 43.
    Zygmunt A, Olfson M, Boyer CA, Mechanic D. Interventions to improve medication adherence in Schizophrenia. Am J Psychiatry. 2002;159:1653–64.CrossRefGoogle Scholar
  44. 44.
    Butler JA, Peveler RC, Roderick P, Smith PW, Horne R, Mason JC. Modifiable risk factors for non-adherence to immunosuppressants in renal transplant recipients: a cross-sectional study. Nephrol Dial Transplant. 2004;19:3144–9.CrossRefGoogle Scholar
  45. 45.
    Chilcot J, Spencer BW, Maple H, Mamode N. Depression and kidney transplantation. Transplantation. 2012;97:717–21.CrossRefGoogle Scholar
  46. 46.
    National Registry of Diseases Office, Singapore. Singapore Renal Registry annual report (internet). 2015. Accessed 4 Nov 2017.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Konstadina Griva
    • 1
    Email author
  • Hui Ling Michelle Neo
    • 2
  • Anantharaman Vathsala
    • 3
  1. 1.Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of MedicineImperial College & Nanyang Technological UniversitySingaporeSingapore
  2. 2.Department of Psychological MedicineNational University Health SystemSingaporeSingapore
  3. 3.National University Centre for Organ TransplantationNational University Health SystemSingaporeSingapore

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