The Role of Nature Versus Nurture in Medication Nonadherence

Medication nonadherence is a critical issue in healthcare, affecting treatment outcomes, increasing the risk of disease complications, and driving up healthcare costs unnecessarily. Despite the best efforts of medical professionals to prescribe effective treatments, a significant number of patients fail to take their medications as directed. This phenomenon raises an important question: what factors contribute to medication nonadherence, and how much do nature (genetics) and nurture (environmental influences) play a role?

When we consider nature in the context of medication nonadherence, we are referring to the inherent, biological, and genetic factors that may influence a person’s ability or willingness to take medication as prescribed². While limited research directly links genetics and medication adherence, the development of certain conditions do have a genetic risk, such as depression and schizophrenia³. Depression, for example, is commonly associated with a lack of motivation, which may reduce a person’s ability to consistently take their medication^4,5. Genetic predispositions to certain mental health conditions can therefore indirectly contribute to medication nonadherence.

Genetics also influence how individuals metabolize and respond to medications⁶ – some people may have genetic risk factors that cause medications to be less effective or produce intolerable side effects, which can subsequently lead to nonadherence. Bad side effects due to genetic factors may cause a person to discontinue their daily medication if they feel they outweigh the benefits of taking it. 

On the other hand, nurture refers to the environmental, social, and behavioral factors that shape a person’s decisions and health behaviors, including medication adherence². These factors often interact with a person’s genetic predispositions, which can influence their ability (or willingness) to stay on track with treatment regimes. Psychological and emotional factors are powerful drivers of medication nonadherence⁷ – stress, stigma (especially in the case of chronic conditions like HIV or mental illness^8,9), and feelings of hopelessness or frustration can all make it more difficult for patients to follow through on their treatment plan. Seeking support from mental health professionals or counselors can help patients mitigate these challenges.

In the clinical trial setting, the debate between nature and nurture often plays an important factor in the success or failure of studies, potentially hindering the development of new medicines¹⁰. When clinical trials fail to account for these complexities, these may produce misleading results, dismissing potentially efficacious drugs simply because a diverse patient population has not been selected, which, both in terms of genetics and life experience, can lead to unnecessary failures, leaving patients without access to potentially life-changing treatments. In addition to this, participants failing to adhere to treatment plans has significant impacts on clinical trial outcomes and obscure and hinder results, leading to inaccurate conclusions about a drug’s efficacy¹¹. Such oversights ultimately delay the availability of new medications that could benefit diverse patient populations, reinforcing the need for a more nuanced approach in trial design.

It’s clear that both genetic (nature) and environmental (nurture) factors play essential roles in medication adherence, but it’s important to remember that these factors are not isolated. Rather, they often interact with one another in complex ways. For example, a person with a genetic predisposition to depression may be more vulnerable to environmental factors such as financial stress or lack of social support, making them even more likely to neglect their medications¹². Conversely, someone without a genetic risk for mental health issues may be less affected by the same environmental challenges, leading to better adherence.

Understanding how these factors interact is crucial for developing more effective strategies to address medication nonadherence. By recognising the role of both nature and nurture, healthcare providers and the broader healthcare industry can adopt a more personalised approach to treatment. This could involve genetic testing to determine the best medication for a patient or providing additional social support to help individuals overcome external barriers to adherence. In some cases, interventions which focus on the environmental or social aspects of medication adherence might even help mitigate genetic predispositions. For instance, improving health literacy, providing emotional support, or offering financial assistance may help a patient overcome barriers that are influenced by both nature and nurture.

References

1. Osterberg, L., & Blaschke, T. (2005). Adherence to medication. New England Journal of Medicine, 353(5), 487–497. https://doi.org/10.1056/nejmra050100 
2. Sravanti, Lakshmi. “Nurture the Nature.” Indian Journal of Psychiatry, vol. 59, no. 3, 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5659093/, https://doi.org/10.4103/psychiatry.indianjpsychiatry_341_17.
3. Matosin, D. (2023, March 28). Genetic link to depression and schizophrenia confirmed in UOW led study. University of Wollongong Australia. https://www.uow.edu.au/media/2023/genetic-link-to-depression-and-schizophrenia-confirmed-in-uow-led-study.php#:~:text=%E2%80%9CThe%20FKBP5%20gene%20one%20of,of%20developing%20a%20mental%20illness
4. Grenard, J. L., Munjas, B. A., Adams, J. L., Suttorp, M., Maglione, M., McGlynn, E. A., & Gellad, W. F. (2011). Depression and medication adherence in the treatment of chronic diseases in the United States: a meta-analysis. Journal of general internal medicine, 26(10), 1175–1182. https://doi.org/10.1007/s11606-011-1704-y
5. Kleinsinger F. (2018). The Unmet Challenge of Medication Nonadherence. The Permanente journal, 22, 18–033. https://doi.org/10.7812/TPP/18-033 
6. Lynch, Shalini. “Genetic Makeup and Response to Drugs – Drugs.” MSD Manual Consumer Version, July 2022, www.msdmanuals.com/home/drugs/factors-affecting-response-to-drugs/genetic-makeup-and-response-to-drugs.
7. Bąk-Sosnowska, Monika, et al. “The Influence of Selected Psychological Factors on Medication Adherence in Patients with Chronic Diseases.” Healthcare (Basel, Switzerland), vol. 10, no. 3, 24 Feb. 2022, p. 426, pubmed.ncbi.nlm.nih.gov/35326906/, https://doi.org/10.3390/healthcare10030426.
8. Semahegn, A., Torpey, K., Manu, A., Assefa, N., Tesfaye, G., & Ankomah, A. (2020). Psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-analysis. Systematic reviews, 9(1), 17. https://doi.org/10.1186/s13643-020-1274-3.
9. National Institute of Mental Health. (2023). Mental illness. U.S. Department of Health and Human Services, National Institutes of Health. https://www.nimh.nih.gov/health/statistics/mental-illness.
10. Farrell, B. “Efficient Management of Randomised Controlled Trials: Nature or Nurture.” BMJ, vol. 317, no. 7167, 31 Oct. 1998, pp. 1236–1239, https://doi.org/10.1136/bmj.317.7167.1236. Accessed 14 June 2020.
11. Shiovitz, Thomas M., et al. “Mitigating the Effects of Nonadherence in Clinical Trials.” The Journal of Clinical Pharmacology, vol. 56, no. 9, 22 Jan. 2016, pp. 1151–1164, https://doi.org/10.1002/jcph.689.
12. Alshaya, Dalal Sulaiman. “Genetic and Epigenetic Factors Associated with Depression: An Updated Overview.” Saudi Journal of Biological Sciences, vol. 29, no. 8, May 2022, p. 103311, https://doi.org/10.1016/j.sjbs.2022.103311.