Rx Minute: Alzheimer's and Primary Nonadherence

Failure to Fill Prescriptions & Developing an Alzheimer's Vaccine

The Problem of Failure to Fill Prescriptions

Successful treatment of disease requires that medication therapy is used as prescribed.  Yet, medicines commonly are not used as directed, leading to poor clinical outcomes and ultimately, higher health care costs.  Taking medications as prescribed begins with a discussion with a physician, receipt of a recommended prescription, and picking up the prescription at the pharmacy.  The failure of patients to pick up  prescriptions, typically referred to as primary non-adherence, is often ignored in the broader discussion of appropriate medication therapy. Primary non-adherence has not been researched as extensively as secondary non-adherence, which refers to the discontinuation of therapy after an initial use.  A recent study published in the American Journal of Managed Care examined the prescription fill rate for patients in an integrated health care system who received prescriptions for medications in one of ten therapeutic drugs areas.[1] Findings demonstrated that a substantial portion of patients do not fill prescriptions recommended for initiation, with approximately 1 in 5 patients not picking up their medications after 2 weeks.

Among the 398,025 patients meeting the selection criteria, 569,095 prescriptions were written during the 3-month study period.  The overall rate of primary non-adherence, or failure to fill an initial prescription was 9.8%.  This rate varied, however, across the ten drug groups and was highest for osteoporosis medications (22.4%) and antihyperlipidemics (22.3%).  At the opposite end of the spectrum, anti-infectives (2.9%), anticoagulants (4.1%), and antiasthmatics (5.6%) were associated with low levels of primary non-adherence.  Individuals receiving prescription medications associated with acute health conditions were significantly less likely to display primary non-adherence than were patients receiving prescriptions for medications associated with chronic conditions.  Primary non-adherence rates were also found to vary based upon patient characteristics. Patients with baseline comorbidities, no prior fill history, of African American or Hispanic race/ethnicity, or taking prescriptions for asymptomatic conditions were more likely to not fill their prescriptions.  A stratified analysis demonstrated that effects differed based on whether medications were used to treat chronic or acute conditions.

The results of this study should be informative to both healthcare providers, policy makers, and other stakeholders.  It is essential to understand how primary nonadherence varies by patient characteristic, therapeutic area, and care setting. Additional research is needed to assess the implications on future clinical and economic outcomes for patients and insurers.

Progress in developing an Alzheimer’s Vaccine

Alzheimer’s research is extremely complex and researchers have faced setbacks in recent years. New research, however,offers new hope with a treatment in development that has the potential to treat or prevent Alzheimer’s disease.  A recent article published in the Proceedings of the National Academy of Sciences (PNAS) describes how repeated systemic injections of monophosphoryl lipid A (MPL) in mice with Alzheimer’s symptoms led to a reduction in Alzheimer-related brain degeneration and an increase in cognitive function.[2]  These findings suggest that MPL holds great promise as an effective treatment or vaccine for humans. 

Alzheimer’s is a neurodegenerative disease in which plaques of amyloid beta and neurofibrillary tangles accumulate in the brain.[3]  These plaques and tangles accumulate at abnormal levels in Alzheimer’s patients and are believed to interfere with brain function by blocking communication among nerve cells and disrupting cell processes.  In the PNAS study researchers found that MPL stimulates the brain’s immune cells to destroy amyloid plaques. 

When mice with Alzheimer’s symptoms were given weekly injections of MPL for 12 weeks, their brains had up to 80% fewer plaques.  In addition, these mice demonstrated significant improvements in cognitive function during spatial learning and memory tests.  Though the safety of the MPL treatment regimen as used in the study still needs to be confirmed, MPL has been used safely in humans for many years as an adjuvant in several vaccine formulations. 

The researchers envision MPL serving two functions: a treatment for Alzheimer’s and a preventive measure against the disease.  “When our team started working on Alzheimer’s disease a decade ago, our goal was to develop better treatment for Alzheimer’s patients,” said Dr. Serge Rivest, one of the authors of the paper.[4]  “With the discovery today, I think we’re close to our objective.” 


[1] Shin et al. “Primary Nonadherence to Medications in an Integrated Healthcare Setting” Am J Manag Care.  2012;18(8):426-434

[2] Michaud JP, et al. (2013) Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology. PNAS 110(5):1941-1946.

[3] Alzheimer’s Association. “What is Alzheimer’s”. Retrieved February 1, 2013: http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp

[4] Major step toward an Alzheimer’s vaccine. ScienceDaily. (2012, January 15) Retrieved January 31, 2013, from http://www.sciencedaily.com/releases/2013/01/130115143852.htm

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