The Case

A 40-year-old man was admitted to the hospital after having a seizure. Upon admission, the patient, a pharmacology-trained research PhD, stated that this was his first seizure. His review of symptoms and physical examination were unremarkable. He denied the use of alcohol, caffeine products, and other recreational drugs; his only regular medications were multivitamins. He did volunteer that he typically had difficulty falling asleep, often taking a single dose of diphenhydramine 25 mg at bedtime. He noted that the diphenhydramine made him somewhat drowsy, but not enough to fall asleep.

In further discussion with the patient, he revealed that these sleep difficulties had substantially increased in the past few weeks to the point that he self-referred to a local sleep disorder program. During his first visit to the program, he was given a prescription for zolpidem. The patient brought the medication to the hospital; review of the label confirmed that the prescription was for zolpidem 10 mg. The printed instructions stated, "Zolpidem 10 mg, 1 at bedtime; if ineffective, take another." Based on his interpretation of these instructions, the patient revealed that he had been regularly taking up to 10 tablets of zolpidem every night and had recently ran out of his supply. A few days after abruptly stopping the medication, he experienced the seizure.

The Commentary

Poor patient awareness or inadequate understanding of medication risks and instructions are often cited as an underlying root cause of medication errors and adverse drug events (ADEs).(1-3) This finding is not surprising, as patients often lack sufficient information to help support proper medication use in ambulatory care settings.(4-6) As this case aptly highlights, even an individual with pharmacological training can make a seemingly simple misstep that ultimately came at a substantial cost. But the problem is much larger and goes far deeper than an errant, unclear label instruction. The issue at hand is the success with which our health care system more broadly guides patients regarding the safe use of medications. A focus on the label may feel myopic, but it is a symbol of patients' reliance on pill bottle labels as a source of crucial information.

The patient in this case, like many patients, would probably have preferred to have received some level of medication counseling from his physician in the sleep disorder program. A first question, then, might be: was there a discussion? Physicians often fail to review even basic drug information with patients at the time of prescribing.(7-9) This is unfortunate, as patients who report having medication-related discussions with their provider are more likely to take medication as prescribed.(10-12) But our health care system often provides limited time for the physician to spend with patients. Moreover, while many guidelines promote medication review and counseling, physicians receive limited guidance on what specifically to tell patients about drugs.(13-15) Specialists like the one seen by our patient may have more time than a typical primary care physician to provide counseling, but it is likely that an insufficient exchange of information and instruction occurred.

Next, our patient leaves the sleep clinic with a prescription for zolpidem. At the point of dispensing, pharmacists also frequently fail to counsel patients on safe medication use, despite federal and state mandates to do so.(16) Furthermore, pharmacists may not be fully aware of why a patient was prescribed the medication (i.e., indication for use) or any spoken instructions provided to the patient by the physician, limiting the potential effectiveness of pharmacist counseling. While the indication for use (i.e., sleep disorder) is probably not the issue in this case, many pharmacists expect physicians to counsel patients to some degree, and if patients do not ask for further guidance, they may not initiate further discussion. A pharmacy practice can also be very busy, and patients may not find it easier to ask for guidance there than in the physician's office. Again, taking a pill may appear to be a seemingly simple task that does not require much external support, but this case illustrates that this is an illusion.

This patient returned from the pharmacy with a filled zolpidem prescription that included vague and misleading instructions. Considering the limited or absence of verbal counseling, he was forced to rely on the written communication he received from the sleep clinic (in our increasingly electronic world, often limited to the prescription now placed within an after-visit summary). In many instances, all he might receive from the pharmacy is a package insert, a container label with auxiliary warnings, and a Medication Guide mandated by the Food and Drug Administration (FDA) for zolpidem. Clearly, the instruction "Zolpidem 10 mg, 1 at bedtime; if ineffective, take another" allows considerable opportunity to interpret the meaning of ineffective, as well as how many times one can repeat the dose and over what interval. Research has repeatedly shown that print materials are unnecessarily complex and difficult to navigate, particularly for patients with limited literacy skills or limited English proficiency.(17-19) Despite being young, in good health, highly educated with training pertinent to medication use, the patient probably received very little informational support from either the prescribing physician or pharmacist, and the material he received was easily misinterpreted. This case, sadly, represents a common scenario with several missed opportunities to avert a dangerous outcome.

While such misadventures can take place regardless of education or health literacy, disparities do exist. Patients with limited literacy skills, multiple co-morbidities, and who are elderly face the greatest risk. Limited literacy skills are significantly associated with more poor recall of medication names and indications and inadequate understanding and use of prescription instructions and precautions.(20-23) Deficits are often greatest for information pertaining to risks and warnings. Older patients also may be more likely to lack sufficient knowledge to safely use prescribed medications, as they are disproportionately affected by limited literacy, cognitive impairment, and co-morbidity. With an increasingly aging United States population and a high prevalence of limited health literacy (between one-third and half of the adult population), reduction of medication errors is both a matter of health equity and patient safety.

How can cases like this one be prevented? How can we create a more standard, effective, coordinated system of patient information for prescription medications? Koh and colleagues propose a Health Literate Care Model (derived from Wagner's Chronic Care Model), which allows health care systems to target changes in the delivery of services to enhance patient self-care.(24) Improvement in health relies equally on patient and provider participation. Following the Health Literate Care Model approach, we must first assume all patients have information needs, large or small. Therefore, all patients may be at risk of confusion and inadequate understanding of prescribed medications.

The Health Literacy Care Model, much like the Chronic Care Model from which it is adapted, emphasizes the importance of a systems approach and encourages increased interactions between patients and providers. Increased dialogue allows patients and providers to be activated and engaged. Physicians need to provide spoken counseling at the time of prescribing a medication, but they need assistance in doing this effectively and efficiently. Furthermore, physicians need to consider the route used to write prescriptions. Due to the advent of e-prescribing, this step may be taken out of the physician's hands, with default instructions selected at the time of order.(25,26) Electronic health record (EHR) tools exist to standardize prescribing, structure counseling, and prompt patients to ask questions.(27) Pharmacists similarly must be more accessible to patients for counseling and carefully attend to what they transcribe onto labels. The challenge is to bridge the gap between community pharmacies and medical practices; opportunities to coordinate patient activities and to share information between two non-communicative health technologies have been difficult, but there may be solutions in the near future thanks to health information exchanges.

Beyond greater patient engagement, there are very pragmatic, health literate solutions that simply need to be disseminated. We know better ways to communicate instructions on a container label, as well as how to provide plain language content on supplemental prescription information provided to patients. The Institute of Medicine (IOM), US Pharmacopeia (USP), National Council for Prescription Drug Programs (NCPDP), and California legislation SB 472 all detail best practices for patient-centered prescription labeling.(28,29) Reducing variability and vagueness of instructions can limit confusion. As an example, a Universal Medication Schedule (UMS) approach promotes using more explicit times per day (i.e., morning and bedtime versus twice daily), and, for as needed medicines (as in this case), to better specify (i) spacing intervals (wait an hour before taking again), and (ii) maximum daily dose (stop: do not take more than two 5 mg tablets). However, in the end the solution must involve the entire continuum of prescribing and dispensing medication, as well as an effort to activate patients to ask questions and stay informed.

Take-Home Points

• Unintentional misuse of prescription medication is very common. A primary root cause of patient confusion is a lack of physician and pharmacist counseling, but also vague, incomplete, or incorrect label instructions.
• Patients should always ask their physician and pharmacist about their medication, including: (i) what is it for, (ii) how do I take it, (iii) how will it treat my condition, and (iv) is there anything else I should know about this medicine.
• Clinicians should ensure patients are adequately counseled regarding the proper use of a medication and specific precautions should be reviewed. Instructions should be written and transmitted to a pharmacy in a manner that does not allow for deviation from proper use.
• Pharmacists should ensure, especially for any medication requiring a Medication Guide or risk mitigation, that patients receive the appropriate information and to review instructions for use and precautions with patients.
• A health system directive should be to impart and enforce new standards for patient-centered labeling, guided by directives of the USP, IOM, NCPDP, and state of California.

Michael Wolf, PhD, MPH Professor, Medicine and Learning Sciences Associate Division Chief–Research Division of General Internal Medicine Feinberg School of Medicine Northwestern University Chicago, IL

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