Too much of a good thing: Medication risks and polypharmacy John Newman, MD, PhD Assistant Professor of Medicine Division of Geriatrics, UCSF 9/18/2018

Disclosures No financial interests to disclose Medication risks and polypharmacy 9/18/2018

Medications and you Medications save lives What is polypharmacy Principles of medications in older adults What you can do [We’ll talk principles, not specific medical advice] Medication risks and polypharmacy 9/18/2018

Medicines save lives Medication risks and polypharmacy 9/18/2018

Treating high blood pressure saves lives HYVET: A randomized trial in adults over 85 years old Treating high blood pressure reduced deaths by 20%! NEJM 2008, 358:1887 Medication risks and polypharmacy 9/18/2018

Treating high blood pressure saves lives SPRINT: A randomized trials of “intensive” blood pressure lowering Aiming for a lower blood pressure goal reduced deaths by more than 20%! (Especially in adults over 75) NEJM 2015, 373:2103 Medication risks and polypharmacy 9/18/2018

Treating high blood pressure keeps us healthy HYVET: Fewer strokes, less heart failure Treating high blood pressure dramatically reduced how many people developed heart failure over time NEJM 2008, 358:1887 Medication risks and polypharmacy 9/18/2018

Too much of anything can harm Medication risks and polypharmacy 9/18/2018

We can’t survive without water But you can drown in too much of it Medication risks and polypharmacy 9/18/2018

Polypharmacy “Polypharmacy” = “Too many medications” Medication risks and polypharmacy 9/18/2018

Problems caused by polypharmacy Side effects Interactions with other medications Difficult to take them all as intended “Prescribing cascades” Expensive “Medicalizing” life Medication risks and polypharmacy 9/18/2018

Polypharmacy is easy Patients have diseases Diseases have guidelines Easy as (following a recipe for) pie Patients have diseases Diseases have guidelines Follow the guidelines Medication risks and polypharmacy 9/18/2018

Polypharmacy is easy Example: A 79-year-old woman with five common diseases: Diabetes COPD/emphysema High blood pressure Osteoporosis Osteoarthritis JAMA 2005: 294: 716 Medication risks and polypharmacy 9/18/2018

Polypharmacy is easy Optimal guideline-driven therapy: 12 medications 19 doses 5 times of the day Medication risks and polypharmacy 9/18/2018

How many medications do we take? Community-dwelling older adults: 28% take 5 or more medications Nursing home residents: Up to 74% take 9 or more medications Jokanovic JAMDA 2015; Beloosesky Clin Interv Aging 2013 Medication risks and polypharmacy 9/18/2018

Many of these may not be helpful More medications often means more inappropriate medications: Potentially unsafe, ineffective, unnecessary, or duplicative Steinman et al., JAGS 2008 Medication risks and polypharmacy 9/18/2018

Principle: Diminishing benefits and increasing harms Medication risks and polypharmacy 9/18/2018

Each medication adds a smaller benefit… The first medication you take for diabetes, blood pressure, etc. has the biggest clinical benefit. Each additional medication may still help, but not as much. Diminishing marginal benefit Effect size Number of meds Medication risks and polypharmacy 9/18/2018

…and an increasing risk of harm Falls Cognitive decline Delirium Hospitalization Med interactions Side effects Incorrect use Etc etc… Increasing marginal risks Diminishing marginal benefit Effect size Number of meds Medication risks and polypharmacy 9/18/2018

Where you and your doctor should be! Choose wisely! Falls Cognitive decline Delirium Hospitalization Med interactions Side effects Incorrect use Etc etc… Increasing marginal risks Diminishing marginal benefit Effect size Where you and your doctor should be! Choose wisely! Number of meds Medication risks and polypharmacy 9/18/2018

Principle: Goldilocks Medication risks and polypharmacy 9/18/2018

Treatments should be just right Older adults often benefit enormously from treating diseases like high blood pressure or heart disease These diseases and their dreaded effects, like strokes or heart attacks, are more common in older adults But older adults can also be harmed by over-treatment, which at extremes can be as dangerous as the disease being treated Medication risks and polypharmacy 9/18/2018

Goldilocks: U-shaped curves Risk or Outcome (e.g. death) Not enough treatment Too much treatment Just right! Intensity of treatment Medication risks and polypharmacy 9/18/2018

Goldilocks: U-shaped curves Risk or Outcome (e.g. death) Blood pressure too high = Strokes Heart attacks Blood pressure too low = Falls Strokes Just right! Intensity of treatment Medication risks and polypharmacy 9/18/2018

Example: Blood pressure and kidney disease Study of 650,000 older veterans with high blood pressure and kidney disease How did their treated blood pressure affect their risk of dying? Kovedsy et al., Annals IM 2013 Medication risks and polypharmacy 9/18/2018

Principle: Everyone gets side effects, but older adults get them worse Medication risks and polypharmacy 9/18/2018

Why are side effects worse in older adults? Slower to metabolize/clear medications from the body Reduced kidney function Reduced liver function Change/decrease in volume of distribution More adipose tissue, less total body water More interactions Polypharmacy is common More diseases Side effects more likely to be significant Less overall physiological resilience Medication risks and polypharmacy 9/18/2018

Young adult feels a bit dizzy, older adult falls Physiological changes make the elderly less able to cope with perturbations caused by drugs (or anything else) Range of OK Age This is called “homeostenosis”, or a narrowing (stenosis) of the ability to maintain homeostasis Medication risks and polypharmacy 9/18/2018

Why are side effects worse in older adults? How does a side effect (dizziness from low blood pressure) interact with changes from age to cause a fall? Vascular: Reduced arterial compliance Cardiac: Reduced maximum heart rate, sick sinus/bradycardia Renal: Less able to concentrate urine, prone to dehydration Vascular: Immobile, blood pools in venous insufficient legs during prolonged seated period Muscles: Reduced muscle mass and strength, unable to recover from near-fall Medication risks and polypharmacy 9/18/2018

Corollary: A new symptom is a medication side effect until proven otherwise Medication risks and polypharmacy 9/18/2018

Watch out for the “prescribing cascade” High blood pressure – prescribe amlodipine Next visit: leg swelling – prescribe furosemide for heart failure Next visit: urinary incontinence – prescribe oxybutinin Next visit: confusion – dementia? Three new diagnoses, three new medications “Boy, Dad is not doing so well” Medication risks and polypharmacy 9/18/2018

Watch out for the “prescribing cascade” High blood pressure – prescribe amlodipine Next visit: leg swelling – prescribe furosemide for heart failure Next visit: urinary incontinence – prescribe oxybutinin Next visit: confusion – dementia? All side effects! The first step should be to stop/change amlodipine Medication risks and polypharmacy 9/18/2018

What can you do? Medication risks and polypharmacy 9/18/2018

Why am I taking this? Medication risks and polypharmacy 9/18/2018

Why do we take medications? Disease Risks Symptoms What is most important to you? Medication risks and polypharmacy 9/18/2018

Why do we take medications? Bad: “I have X, therefore I must take Y” Disease Risks Symptoms Good: Prevent strokes Good: Treat tremor What is most important to you? Is it worth possible side effects? How do I weigh it against other medications? Medication risks and polypharmacy 9/18/2018

Beware zombie medications No one knows where it came from… No one knows what it’s for… Is anyone brave enough to stop it? Zombie medications are especially common after ER visits or hospitalization. Often they were never meant to be continued long-term. Medication risks and polypharmacy 9/18/2018

Is this the right medicine? Medication risks and polypharmacy 9/18/2018

Ask your doctor about the Beers Criteria Beers Criteria is from the American Geriatrics Society List of medications that should be used with caution specifically in older adults Updated every few years by national experts http://www.healthinaging.org/medications-older-adults/ Medication risks and polypharmacy 9/18/2018

2015 Beers: Ten groups of medicines Non-steroidal anti-inflammatory drugs (NSAIDs) Digoxin (Lanoxin) Certain diabetes drugs Muscle relaxants Certain anxiety and insomnia drugs Certain anticholinergic drugs Meperidine (Demerol) Certain antihistamines like diphenhydramine Antipsychotics Estrogen pills and patches Medication risks and polypharmacy 9/18/2018

Ask your doctor about the Beers Criteria Medication risks and polypharmacy 9/18/2018

Most serious problems are from a few meds Blood thinners - bleeding Diabetes medicines – low blood sugar Inherent in how the medicines work Sudden and serious Budnitz et al., NEJM 2011 Medication risks and polypharmacy 9/18/2018

With great power… Powerful medicines save lives Poweful medicines carry powerful risks Know how you affect how the medicine works Diet, monitoring, timing, etc. Know how to identify serious side effects early Tell your doctor everything about these medicines Ask for help Medication risks and polypharmacy 9/18/2018

Is this the right medicine for me? Medication risks and polypharmacy 9/18/2018

Precision medicine: Is it right for you? Will this interact with my warfarin? How will this work with the other medicine I take for that? Do any of my other medical problems affect this? What about my kidneys? Your medical history Your other medicines Your priorities How do I weigh the expected benefit vs the possible risks? How would the common side effects affect me? Is this my most important medicine, or the 10th most important? Medication risks and polypharmacy 9/18/2018

For every new medicine, and at least once a year for all medicines: “Why am I taking this?” “Do I still need it?” “Is it still the best choice?” Medication risks and polypharmacy 9/18/2018

Make sure all of your doctors know everything you take Medication risks and polypharmacy 9/18/2018

Keep all of your doctors in the know Safe prescribing requires knowing everything you take Avoid duplication, interactions, etc. Bring your medications (or an updated list) to every appointment Tell each doctor about any recent changes Ideally, pick one doctor do all the prescribing Medication risks and polypharmacy 9/18/2018

Tell you doctors about any problems! Trouble with insurance or the pharmacy Trouble with affording medications Need help organizing or taking medications? Possible side effects If for a symptom, does the medicine help? If you don’t tell them, they’ll never know! Medication risks and polypharmacy 9/18/2018

Principles of medications for older adults Diminishing benefits and increasing harms Both under-treatment and over-treatment can cause harm Side effects are often worse in older adults A new symptom is a medication side effect until proven otherwise Medication risks and polypharmacy 9/18/2018

What you can do For every new medication, and at least once a year for all medications: Why am I taking this? To prevent something bad, or to help me feel better? Do I still need to take this? Is it important enough to take? Is this the right medication? American Geriatrics Society Beers Criteria Have I changed? Make sure all of your doctors know everything you take Tell your doctors of any problems with your medications Medication risks and polypharmacy 9/18/2018

Less is often more! Medication risks and polypharmacy 9/18/2018

Thank you! geriatrics.ucsf.edu healthinaging.org Medication risks and polypharmacy 9/18/2018