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Polypharmacy: Navigating Risk and Benefit in a pill-taking society

Key points: Medications are metabolized in the body to produce an intended effect along with secondary effects. With an increase of medications taken, there is an increased risk of drug to drug interactions and potentially serious harm. Multiple medications, or polypharmacy, are often seen in an older age cohort, individuals with significant mental health issues and those that have obesity-related conditions. Finding a safe level of risk and benefit often avoids harmful side effects and health risks.

The new patient visit, and subsequent visits, to a primary care physician is often an ideal time to discuss medications. As the clinician is becoming acquainted with a patient, they may begin to discuss the reasons and necessity for each medication. A patient with a chronic condition, such as diabetes or hypertension, will often already be taking 2 to 3 medications.  I start getting more concerned for harm when I see a patient on more than 4 or 5 medications. 

Not surprisingly, however, is that the proportion of patients with polypharmacy has grown with the aging society.  In one longitudinal survey of persons ages 62 to 85 published in the JAMA internal medicine, more than a third of patients were taking at least five prescriptions.  In this older cohort, chronic conditions, such as hypertension, diabetes and vascular disease were common. Their bodies metabolize medications differently, on account of an aging kidney, liver and differences in subcutaneous tissue and protein levels. It is for this reason, that the elderly population is at a higher risk for harm.

Multiple medications could increase the risk for adverse drug reactions (ADRs) and drug-to-drug interactions, some of which can have serious health implications, including increase risk of falls, decline in functional status and delirium. It is estimated that as many as 10% of emergency room visits are attributable to an ADR and a patient who is taking more than 4 medications have a near 90% risk of experiencing an ADR.  There can even be significant cost issues, as a retiree is cutting into their savings to cover the medication expenses.  This has become increasingly more costly, as insurance companies are reducing their expenses by not covering newer agents.

Reasons for polypharmacy include 1) having multiple providers, 2) taking additional over-the-counter agents which are sometimes construed as harmless, 3) a new health problem or treatment for a temporary process, e.g. antibiotics in the setting of a new infection. Often underlying polypharmacy is an unaddressed health behavior that contributes to the maintenance of a dis-ease state, e.g. ongoing smoking, alcohol use and emotional eating. (see Behavior and Health and Behavior and Eating posts)

Polypharmacy can occur when a patient sees more than one provider – maybe a cardiologist, an endocrinologist or a psychiatrist – who may not thoroughly review non-specialty-related medications. Sometimes, the specialist will use two medications for complimentary effect, e.g. treating high blood pressure. There may not be communication between providers if a medication addition or change is decided upon.  A person with a significant mental health condition is particularly at risk, because they are often placed on more than one medication.  Some of these medications, for instance anti-epileptics or medications for bipolar disorder can increase the risk of developing metabolic syndrome including diabetes. A patient with chronic pain may be treated on multiple medications, such as tramadol, cymbalta or hydrocodone which have numerous drug interactions. 

Patients may add to their prescribed medication regimen with over-the-counter agents or herbals that are otherwise thought of as harmless given that they do not require a prescription. Medications like “sleep aides” often contain diphenhydramine (benadryl) which can contribute to multiple drug interactions, confusion and urinary retention. Cimetidine (pepcid) can be associated with confusion or delirium in the elderly. A list of potentially harmful to the medications The Beer’s List is included and contains several over the counter agents. A few links are included at the end of the post.


Consequences of Polypharmacy*

  1. Increased Cost for healthcare – imagine that a retired person receiving a minimum income is asked to take a brand medication at top dollar (pharmaceutical companies will provide coupons but these will not be applicable to medicare). The average cost of these is approaching $5,800 a year. Imagine having to pay for even a portion of this on a social security income.
  2. Adverse Drug Reactions and Drug-to-Drug Interactions
  3. Problems with adherence – This is understood when someone is taking more than one medication and more than one time interval daily.
  4. Cognitive Impairment and Delirium – It doesn’t take a lot of a medication that has soporific or CNS side effects (sleep-inducing) to effect an elderly person who ends up with higher doses of drug distributed in the blood because of changes in pharmacokinetics (the way a drug is metabolized by the body)
  5. Falls – There is a greater likelihood from falling because of drowsiness or dizziness.
  6. Functional Status
  7. Urinary Incontinence – some medications can lead to urinary retention (benadryl, opiates, some dementia medications) or increased urination (diuretics).
  8. Nutritional Impact – some medications can increase risk of vitamin deficiencies, e.g. proton pump inhibitors, such as omeprazole, can lead to vitamin b12 deficiency and is linked to increased risk of osteoporosis.

*Maher et al. Clinical Consequences of Polypharmacy in Elderly. 2014. Expert Opin Drug Saf. Jan 13 (1): 10.1517.


Questions to Review when considering Polypharmacy

The following questions are useful in approaching polypharmacy for both patient and clinician alike. The paragraphs that follow will provide greater detail.

  1. Does patient need the prescribed medication?
  2. Number needed to treat? Number needed to harm?
  3. Are there any redundancies in the medications?
  4. Are there any drug-to-drug interactions?
  5. Does the medication need to be taken every day e.g. sleep medications, pain medications and is there a safer alternative?
  6. Is there an underlying behavior that is causing problem that is being medicated?
  7. Are there any preventive options?

Besides asking the obvious question, whether a patient really needs to take every medication, there is also the question of what is really the benefit of the medication. The number needed to treat (NNTT) and number needed to harm (NNTH) are useful tools to determine the benefits and risks of a medication. The higher the number is the less beneficial a medication. A detailed list is available with the link – http://www.thennt.com/home-nnt/ Unfortunately, most medications are not very effective in their intended activity and are often more likely to cause side effects. For instance, the HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia (high cholesterol) which many cardiologists would joke ” we need to put them in the water” during my training are more likely to harm than to help: NNTT 1 in 104 (preventing cardiac disease) and 1 in 154 (preventing stroke) and NNTH 1 in 10 (muscle damage) and 1 in 50 (diabetes association*). And that is after taking them for 5 years!! The data doesn’t look much better after taking them for a heart attack. I would suggest that patients check their medications with the link.

During the first and subsequent office visits, it is often possible to begin whittling down the medication lists to the most effective and least harmful number of medications.  I often will have patients bring all of their medications in a bag to the clinic.  As I run through the medications, I ensure that every medication has a justifiable indication, there is no obvious redundancy and include the prescriber and specialty, and the dose. I then run a check of drug-to-drug interactions on Epocrates (which has an online format as well).  If there are any redundant medications or those with no clear indication, e.g. the use of a “statin” in an advanced elderly patient, I will collect the medications and dispose of them or discuss with the patient regarding titration off or to a lower dose. Most patients are relieved (and a little surprised!) with these reductions and sometimes report an improvement in their health, as significant and subtle medication side effects dissipate after the medication is stopped.     

“Doctor, can I get a dose of #### for a yeast infection…”
It is also important that a physician review medications prior to considering a new prescription.  The addition of antibiotics to a patient medication list, although usually for a short course, has implications as well.  From what a seemingly innocuous course of an antibiotic could arise multiple drug-to-drug interactions and ADRs.  For example, many patients will request fluconazole because the topical creams can be inconveniencing and have mixed results.  The treatment is usually a one-time tablet of 150mg.  There are more than 600 reported drug-to-drug interactions with fluconazole, one-fifth of which can be severe or life threatening (though rare).  The metabolism of fluconazole in the liver may impact that of other medications used in chronic diseases, such as statins or cardiac medications, increasing levels of metabolites of these medications in the bloodstream.  Patients who take hydrocodone or oxycodone may have an increase in levels of metabolite in their system after taking fluconazole, increasing risk of harm. The anticoagulant Coumadin levels increase when fluconazole is taken, which increases the risk of bleeding.  When fluconazole is simultaneously prescribed with another cardiac medication amiodarone, there is an increased risk of Q-T prolongation, which is capable of increasing the risk of the life-threatening condition ventricular fibrillation.  Although a few doses of fluconazole is not as likely to cause problems, the risk requires a consideration of whether this medication is safe or an alternate regimen or route (e.g. topical) should be considered. 

Sometimes a medication doesn’t need to be taken on a regular basis and can be taken only as needed. I have had many patients who request taking Ambien (zolpidem) or other agents (e.g. oxycodone, hydrocodone, tizanidine, alprazolam, etc) on a daily basis for sleep or arthritic pain or anxiety issues. As disabling these conditions can be, these are conditions that should not be just blindly treated. It is generally more pro-active to regard these conditions as requiring investigation and therapeutic and lifestyle considerations. For instance, a sleep study may uncover restless leg syndrome or significant sleep apnea. A thorough history and physical may uncover a behavior that is leading to increased neck pain, a condition in which physical and occupational therapy would be more useful. A referral to a counselor can help a person develop better coping skills. Unfortunately, by the time a patient comes to see a new physician, they are often already on the medication every day and have developed a dependence on that medication. A physician’s well-meaning attempts at reducing the medications will be met with resistance and some patients may take their business elsewhere. On the other hand, by taking medications intermittently and only with severe symptoms, dependence and significant side effects can be avoided.

It is not infrequent to see a patient who is taking a statin medication for known heart disease e.g. they suffered a heart attack, and is still smoking. On one side, I might as well tell them to stop taking the statin, because the smoking trumps any medication. That is often the case with behavior. Why piddle around with medications when someone is still doing a harmful behavior? Well – one obvious answer – BEHAVIOR CHANGE IS NOT EASY! and certainly ADDRESSING BEHAVIOR CHANGE IN THE CLINIC is almost USELESS. That is my objective with Your Health Forum – take behavior change out of the clinic and partner physician with the patient! It is incredible how much more effective a successful behavior change, such as quitting smoking and eating natural food rather than processed food, can have on one’s health.

A weight loss of 15 lbs can lead to a reduction of 8.5 and 6.5 mm Hg in the systolic and diastolic blood pressure readings. These changes do not occur in a vacuum. obesity is a systemic resistance problem, the body gradually functions better with ongoing weight loss — less obstructive sleep apnea, less fluid retention, less blood pressure, less insulin resistance, less triglycerides, less uric acid (gout), less knee and ankle pain, and the list goes on. As pointed out in prior posts, the behavior is not “weight loss” – the behavior is healthy eating and breaking the emotional eating cycle.

This goes to the final question of preventive options. A medication comes with risks and benefits. As pointed out earlier, the benefits are limited and there can sometimes be significant side effects. Risk for harm from side effects and drug-to-drug interactions increases with more medications. Behavior change is like a magic bullet to medical conditions that are linked to the behavior. After all, what is more effective than removing the condition?

I have found that, unless a patient is running a high risk of harm — a VERY HIGH blood pressure — coaching them on behavior change may be more useful than prescribing a medication — though a collaborative approach with frequent check-backs is likely to be more effective than a single visit.

My recommendation for anyone that is on multiple medications is to brainstorm on strategies to promote a change in the behavior, to work directly with the physician to weigh the risks and benefits of a medication (check indication, check NNTT/NNTH, run through Beer’s list and look for safer alternatives), ensure that your physician is doing a cross-check on a new or short-term medication and collaborate with your physician on taking a smaller “test-dose” for several days to acquaint yourself with the side effects of the medication.

Thanks for reading and hope you found it useful! Dr. Christopher Cirino




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