We Use Too Many Medications: Be Very Afraid of Interactions

From 2021

I happened to read about the pharmacodynamics of parenteral versus oral furosemide when I came across a unique interaction between this commonest of diuretics and risperidone: Elderly dementia patients on risperidone have twice their expected mortality if also given furosemide. I knew that all atypical antipsychotics can double mortality in elderly dementia patients, but was unaware of the additional risperidone-furosemide risk. Epocrates only has a nonspecific warning to monitor blood pressure when prescribing both drugs.

This is only today’s example of an interaction I didn’t have at my fingertips. I very often check Epocrates on my iPhone for interactions before prescribing, because – quite frankly – my EMR (it was Epic when I wrote this) always gives me an entire screen of fine print idiotic kindergarten warnings nobody ever has time to read in a real clinical situation. (In my case provided by the otherwise decent makers of UpToDate.)

I keep coming back in my thoughts to, and blogging about, drug interactions. And every time I run into one that surprised me or caused harm, I think of the inherent, exponential risks of polypharmacy and the virtues of oligopharmacy.

One conclusion I have come to is that too often the benefit of our prescribed medication is actually too small to justify the drug. The way drugs are approved today is pretty much that they have to bring a 20% or so advantage over placebo for a certain outcome. Other than the drug versus placebo, all other factors are ignored or “controlled for”, which is easier said than done.

But this whole premise seems wrong to me: If pill A is 20% better than placebo at lowering blood pressure, but salt restriction, weight loss, exercise and stress reduction are twice as powerful as pill A, why are we so stuck on prescribing pill A? If a Mediterranean diet lowers cardiovascular risk as much as atorvastatin, why isn’t that a blockbuster/no-brainer intervention?

The health of our nation is not great, in spite of all the pills at our disposal. And the more pills we prescribe, the more we risk interactions: antidepressants and cholesterol pills with blood thinners, gout medicines with cholesterol pills, mood stabilizers with cardiac medications and on and on and on.

May we all take a step back and look at the big picture of what we are doing and where we are heading.

Donald W Light from the Harvard Center of Ethics wrote in 2014:

Few people know that new prescription drugs have a 1 in 5 chance of causing serious reactions after they have been approved. That is why expert physicians recommend not taking new drugs for at least five years unless patients have first tried better-established options, and have the need to do so.

Few know that systematic reviews of hospital charts found that even properly prescribed drugs (aside from misprescribing, overdosing, or self-prescribing) cause about 1.9 million hospitalizations a year. Another 840,000 hospitalized patients are given drugs that cause serious adverse reactions for a total of 2.74 million serious adverse drug reactions. About 128,000 people die from drugs prescribed to them. This makes prescription drugs a major health risk, ranking 4th with stroke as a leading cause of death. The European Commission estimates that adverse reactions from prescription drugs cause 200,000 deaths; so together, about 328,000 patients in the U.S. and Europe die from prescription drugs each year. The FDA does not acknowledge these facts and instead gathers a small fraction of the cases.

There are obviously more recent statistics out there, but this piece struck me because it was published in a forum about ethics. Think about that for a moment: We are subjecting our patients to known and unknown risks of harm with every prescription we issue.