Search Results for 'Interaction '

We Use Too Many Medications: Be Very Afraid of Interactions

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 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.

The Intricacies of Antidepressant Interactions

Once upon a time there were jokes circulating about putting Prozac (fluoxetine) in the drinking water.

The idea was that the modern antidepressants were indicated for most people living in today’s society, and that these drugs were completely safe to use.

Now, these same drugs have so many warnings that they have become increasingly difficult to use in treating the common maladies of depression and anxiety.

The earliest scuttlebutt about Prozac causing suicidal thinking never did go away completely. We were assured that the suicide rate itself did not go up, only thinking about it. Some of that was explained by powerful antidepressants potentially unmasking bipolar illness and causing manic episodes. But a few years later, Paxil (paroxetine) was reported to cause suicidality in adolescents.

Just in the past few months, I was reminded several times about the intricacies of prescribing SSRIs.

A middle aged man on the blood thinner warfarin suddenly developed nosebleeds when his INR shot above the therapeutic range. His psychiatrist had doubled his Prozac two weeks earlier.

An anxious and depressed elderly woman wanted to try an antidepressant, and I gave her a low dose of Lexapro (escitalopram). She told me the following week that she felt tired and listless. I ordered some routine blood taste and her sodium level came back precipitously low. We stopped her Lexapro and she felt better again within a week.

A tall, thin elderly man with Parkinson’s disease and depression wanted to try something for his mood. I searched the literature and prescribed the SSRI with the most data on use in his condition. The following week he felt lightheaded. His blood pressure and pulse were both lower than his baseline, and I ended up cutting his beta blocker in half twice before his vital signs normalized; I had never heard or seen this interaction before.

A middle aged woman with a history of pulmonary emboli had been difficult to regulate on warfarin, and during a recent hospitalization, the doctors had changed her over to the novel anticoagulant Eliquis (apixaban), which doesn’t require any monitoring. When it was time to refill her Zoloft (sertraline), my computer flagged me with a bold, red warning that apixaban and sertraline are a dangerous combination resulting in increased risk for bleeding.

The list of warnings for this class of drug goes on, including effects on pregnancy, heart arrhythmias, seizures, glaucoma, liver disease and diabetes.

Given that their effectiveness is reported to be only marginally better than placebo, I have become increasingly more cautious about prescribing them.

Just this year, though, in Molecular Psychiatry, a new analysis of old data suggests that previous studies had used an ineffective rating system for depression, and that SSRIs are more powerful than we thought.

I remain skeptical. Once bitten, twice shy.

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Osler said “Listen to your patient, he is telling you the diagnosis”. Duvefelt says “Listen to your patient, he is telling you what kind of doctor he needs you to be”.

BOOKS BY HANS DUVEFELT, MD

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