Interventions to tackle medication non-adherence

• Non-adherence to medication is a major cause for rise in mortality, morbidity and overall health costs¹.
• Non-adherence is caused by numerous factors belonging to socioeconomic, patient-related, therapy-related or healthcare system-related requiring multipronged intervention strategies^1,2.
• A combination of educational, behavioral, reminder-based and dose simplification could help in improving medication adherence more effectively ^3,4.

Medication adherence, or the extent to which patients take medications as prescribed, is remarkably low and it has been reported that typically, patients adhere to about 50% of prescribed medications¹. Factors causing medication non-adherence are varied and can be grouped into patient-related, therapy-related, and healthcare system-related¹. Some of the common reasons are forgetfulness, adverse effects, lack of awareness, mental health issues, poor patient-physician relationships, lack of social support, and comorbidities. Suboptimal adherence is associated with increased mortality, morbidity, and healthcare costs¹. With diverse factors contributing to poor medication adherence, interventions to improve adherence are consequently complex, varied, and abundant. The use of technology in monitoring and addressing non-adherence behavior is proving a game changer.

Interventions addressing non-adherence

Improving adherence requires a sustained and dynamic process requiring different interventions, which should be personalized to target the specific reasons due to why patients have not been taking the medication¹. Broadly, the conventional interventions to improve medication adherence can be categorized into the below-mentioned strategies⁴.

• Patient education: Personalized educational interventions delivered in the form of in-person or telephonic verbal information as well as printed or audio-visual materials. It is most successful if initiated at the time of diagnosis and followed up through the course of treatment⁴. Strategies that help in medication management by giving access to materials or resources to enhance a patient’s ability to manage their condition. Effective communication of clinical data from the provider to the patient with follow-up phone calls to recommend appropriate adjustments in care should be part of patient education initiatives³.
• Medication regimen management: It includes the strategies that reduce the daily pill burden of patients by reducing the complexity of dosing regimens. It can be done by reducing the dosing frequency or the number of pills taken by using combination pills or “polypill”^3,4. In a real-world study, it was reported that patients with schizophrenia who received LAIs had better medication adherence and lower discontinuation risk than those who had an oral antipsychotic monotherapy⁵.
• Patient Incentives/Reduced Out-of-Pocket Spending: strategies aimed at reducing patients’ out-of-pocket expenses for prescription medications has reported mixed results in improving adherence. It can be done through the provision of positive or negative financial incentives, reduced medication copayments, or improved prescription drug coverage^3,4. Prescribing the generic formulations for the available drugs can also help in reducing cost-related non-adherence in patients (See our article: Prescription costs are key to non-adherence: can generics help?).

• Clinical pharmacist consultation: Co-management of medication through a clinical pharmacist can improve adherence. They can help with closer monitoring of drug administration, improvement in symptoms, management of adverse effects, reminders for medication refills, and boosting belief in the therapy⁴.

• Reminders and prompting mechanisms: strategies that remind patients about medication schedules, refills, or appointments are important tools to improve adherence (For details see our article: Pill reminders: Addressing non-adherence owing to forgetfulness). These interventions incorporate technology to remind (e.g. telephones, videos, cell phones, pagers, emails, short message services SMS), or monitor/remind (e.g., electronic drug monitors, medication event monitoring systems, pillboxes with an alarm system, telehealth devices, etc)³. Several advanced digital interventions like, MEMS and their usefulness in monitoring and assisting in medication management are discussed in detail in our article: Technological advancements and innovations to improve medication adherence.

• Behavioral interventions: These interventions are characterized by cognitive behavioral techniques (CBT) and motivational interviewing that aim to modify the patient’s behavior toward treatment^4,6. Behavioral theories are based on the health belief model (HBM), social-cognitive theory (SCT), and the theory of planned behavior (TPB). These theories share the assumption that attitude and beliefs, as well as expectations of future events and outcomes, are major determinants of health-related behavior and would encourage individuals to choose the action that would lead to positive outcomes⁷. For more on this see: Methods of behavior change in medication non-adherence.

• Enhanced accessibility to healthcare: Accessibility to healthcare remains a challenge for vulnerable patient groups like older age, females, minority races, and mental health patients. Interventions that enhance the accessibility to pharmacies as well as follow-up appointments with a physician, specialist, or psychiatrist can enhance adherence⁸.

Table 1: Advantages and limitations of intervention strategies⁴

Intervention	Description	Advantage	Limitation
Patient education	Generating health litracy	Feasible, available, and generally acceptable to patients.	Time intensive for the physician or other professionals.
Medication Regimen management	Reducing the complexity of dosing	Feasible, available, and generally acceptable to patients.	Requires time from the physician and awareness of patient comorbidities.
Pharmacist consultation	Co-management of therapy via clinical pharmacist	Draws help from other professionals	May not be available in all practices
Cognitive Behavioral therapy	Improving medication-taking behavior	Draws help from other professionals. Addresses the root cause of non-adherence behavior	Requires trained staff and time commitment from patients.
Medication reminders	Reminding medication administration, refills, or appointments	Easy, less labor intensive	Availability and costs. Works if personalized and interactive.
Economic Incentives	Financial incentive to promote adherence	Generally acceptable to patients, easy	Feasibility and scalability

Multidimensional Interventions:

Since the causes of non-adherence to medication for chronic diseases are multifactorial, strategies that use a combination of two or more of the above-mentioned interventions are likely to work better. Interventions that included education, personalized motivational feedback, motivational interviewing, and reinforcement messages that were digitally delivered, were found effective across chronic conditions like asthma, cancer, diabetes, epilepsy, HIV/AIDS, and hypertension. Additional components targeting psychoeducation and cognitive behavioral techniques (CBT) are further recommended to achieve sustainable medication adherence⁹.

A few evidence-based multidimensional interventions for chronic diseases:

• ENDORSE: A randomized control trial that studied the effect of behavioral interventions in conjunction with educational interventions on medication adherence among elderly patients with diabetes, hypertension, dyslipidemia, or coronary artery disease. It was reported that behavioral interventions that comprised systematic education, maintaining a patient diary to mark daily medicine intake and periodic telephone reminders improved medication adherence among older adults¹⁰.

• Patient-centered prescription (PCP): The patient-centered prescription (PCP) model is a multifactorial approach with both behavioral and educational components, the development of patient-specific care plans based on patient’s barriers identified through the qualitative assessment of medication adherence, the active involvement of patients and/or main caregivers with treatment choices, and multidisciplinary collaboration. It includes simplifying the dosing regimen and complexity, reducing inappropriate prescribing and medication burden in patients with multimorbidity, and includes motivational interviewing and pharmacotherapy counseling provided by the hospital pharmacist¹¹.

• MAGIC study: Medication adherence given individual SystemCHANGE study had socioecological model at its core, it focused on changing the behavior by changing the individual’s environment, specifically their support system that can influence medication intake. It provided appropriate solutions while continuously monitoring adherence data and evaluating them. The study reported a very significant improvement in adherence behavior of post-transplant patients as compared to the control group^12,13.

Recommendations for clinicians to improve adherence⁴:

• Anticipate non-adherence: Educate patients about the importance of the therapy and the consequences of not adhering to it.
• Identify suboptimal adherence: through self-report and monitoring for poor disease control. Be vigilant for high-risk patients.
• Intervene during clinic visits: Understand causes of non-adherence and direct towards specific interventions or resources as appropriate.
• Follow-up after clinic visit: Enhance contact with patients with suboptimal adherence to monitoring the effect of interventions.

Recommendations for the health system to improve adherence⁴:

• Help clinicians diagnose non-adherence: Synchronizing the pharmacy claim data with electronic health records to enable easy diagnosis.
• Provide infrastructure to address non-adherence: Making available appropriate infrastructure like electronic pill bottles and electronic monitoring devices for non-adherence patients.
• Provide resources and trained professionals: Support staff like trained nurses or clinical pharmacists and behavioral specialists to impart interventions for ameliorating non-adherence to therapy.

Conclusions

Multifaceted interventions are required for improving medication adherence. It should include efforts to improve patients’ understanding of medication benefits, access, and conviction in their provider and health system. Improving providers’ recognition and understanding of patients’ beliefs, fears, and values, as well as their own biases is equally necessary to achieve increased medication adherence and overall population health².

“Patient adherence should be acknowledged as a critical health care issue, and a multidisciplinary approach to education and management in this area should be established” –  Professor John Weinman.

References

1.  Gil-Guillen VF, Balsa A, Bernardez B, et al. Medication Non-Adherence in Rheumatology, Oncology and Cardiology: A Review of the Literature of Risk Factors and Potential Interventions. Int J Environ Res Public Health. Sep 23 2022;19(19)doi:10.3390/ijerph191912036

2.  Brown MT, Bussell J, Dutta S, Davis K, Strong S, Mathew S. Medication Adherence: Truth and Consequences. Am J Med Sci. Apr 2016;351(4):387-99. doi:10.1016/j.amjms.2016.01.010

3.  Anderson LJ, Nuckols TK, Coles C, et al. A systematic overview of systematic reviews evaluating medication adherence interventions. Am J Health Syst Pharm. Jan 8 2020;77(2):138-147. doi:10.1093/ajhp/zxz284

4.  Kini V and Ho M. Interventions to ImproveMedication Adherence A Review. JAMA. 2018 Dec 18;320(23):2461-2473. doi: 10.1001/jama.2018.19271.

5.  Greene M, Yan T, Chang E, Hartry A, Touya M, Broder MS. Medication adherence and discontinuation of long-acting injectable versus oral antipsychotics in patients with schizophrenia or bipolar disorder. J Med Econ. Feb 2018;21(2):127-134. doi:10.1080/13696998.2017.1379412

6.  Costa E, Giardini A, Savin M, et al. Interventional tools to improve medication adherence: review of literature. Patient Prefer Adherence. 2015;9:1303-14. doi:10.2147/PPA.S87551

7.  Munro S, Lewin S, Swart T, Volmink J. A review of health behaviour theories: how useful are these for developing interventions to promote long-term medication adherence for TB and HIV/AIDS? BMC Public Health. Jun 11 2007;7:104. doi:10.1186/1471-2458-7-104

8.  Ruddy K, Mayer E, Patridge A. Patient adherence and persistence with oral anticancer treatment.CA Cancer J Clin. 2009 Jan-Feb;59(1):56-66. doi: 10.3322/caac.20004.

9.  Konstantinou P, Kassianos AP, Georgiou G, et al. Barriers, facilitators, and interventions for medication adherence across chronic conditions with the highest non-adherence rates: a scoping review with recommendations for intervention development. Transl Behav Med. Dec 31 2020;10(6):1390-1398. doi:10.1093/tbm/ibaa118

10. Raj JP, Mathews B. Effect of behavioral intervention on medication adherence among elderly with select non-communicable diseases (ENDORSE): Pilot randomized controlled trial. Geriatr Gerontol Int. Nov 2020;20(11):1079-1084. doi:10.1111/ggi.14032

11. Gonzalez-Bueno J, Sevilla-Sanchez D, Puigoriol-Juvanteny E, Molist-Brunet N, Codina-Jane C, Espaulella-Panicot J. Improving medication adherence and effective prescribing through a patient-centered prescription model in patients with multimorbidity. Eur J Clin Pharmacol. Jan 2022;78(1):127-137. doi:10.1007/s00228-021-03207-9

12. Russell CL, Moore S, Hathaway D, Cheng AL, Chen G, Goggin K. MAGIC Study: Aims, Design and Methods using SystemCHANGE to Improve Immunosuppressive Medication Adherence in Adult Kidney Transplant Recipients. BMC Nephrol. Jul 16 2016;17(1):84. doi:10.1186/s12882-016-0285-8

13. Russell CL, Hathaway D, Remy LM, et al. Improving medication adherence and outcomes in adult kidney transplant patients using a personal systems approach: SystemCHANGE results of the MAGIC randomized clinical trial. Am J Transplant. Jan 2020;20(1):125-136. doi:10.1111/ajt.15528