Statins and Placebo Produce Similar Side Effects

A clever study design at the virtual scientific sessions of the American Heart Association showed that half of the patients taking statins for LDL cholesterol-lowering that reported side effects from treatment were convinced to go back on their statins when they experienced similar side effects while on placebo.

In this exclusive MedPage Today video, Maryann McLaughlin, MD, of the Icahn School of Medicine at Mount Sinai in New York City, breaks down the results of the SAMSON trial and discusses ways to help patients prepare for this potential "nocebo effect."

Following is a transcript of her remarks:

The SAMSON trial was presented recently at the American Heart Association meetings and was a very interesting trial because it was a trial of only 60 participants over the course of 12 months. And the idea was to see whether the patients who have taken statin medications, and who have had side effects to statin medications, would still have similar side effects if they took a placebo pill or if they took nothing. So when we talk about the nocebo effect it's different than the placebo effect. Most people have heard about the placebo effect. And if you look at the Latin for placebo, it means "I please," and nocebo means "I harm."

So in prior studies of looking at drug therapy trials, when patients are given placebos, and they don't know whether it's a real pill or a sugar pill, when they think that it might be helpful to them, they actually report more positive outcomes. The placebo effect is thought to be due to some changes in neurotransmitters in the brain. So if your brain thinks that hard enough, maybe you will have increased levels of dopamine or oxytocin or other pleasurable hormones that will maybe make you feel better. The nocebo effect is what's being evaluated in this study. And in fact, in this study they show that patients did a trial of either a statin medication for a month at a time then a placebo effect, which is a pill that looked like the statin. And then a period of no pill at all. And during that timeframe, they were asked to report their symptoms.

So, they kept track of that. So they knew when they were taking nothing, but they didn't know whether the pills they were taking were in fact, the real statin or a placebo. And importantly, there was a statistically significant correlation of patients having reported side effects to the placebo pill compared with their statin medication.

And so the bottom line was to say that there is a negative effect when people expect that they're going to feel or have a certain side effect to medication. In fact, they report that. So what do we say, how do we take home this effect? Well, number one is that there are neurobiologic mechanisms for even this nocebo effect. There is a neuroreceptor called cholecystokinin, it's a neurotransmitter that can be associated with negative feelings. And it has been shown in some studies that when you have the nocebo effect that you have higher levels of this neurotransmitter. Interestingly, anxiolytic medications have been shown to reduce that effect.

So when it comes down to practice, patients with underlying depression or anxiety disorders may be more prone to have this nocebo effect. How can we reduce this effect? One is to explain, to emphasize the positive effects of the drug and avoid over-emphasizing the adverse effects. So act in a positive direction. Explain the mechanism of drug actions. And manage expectations of all drugs, by having an open dialogue, and saying that this side effect profile has happened in some people, but it's not that common. Or if that's the truth you can say, you expect them not to have that side effect. By being positive in your response when you're administering the medications, you might see a more positive response in the patients when they take the medications.

Now we know with statins, there are some genetic predispositions to patients who do have side effects. So patients of Ashkenazi Jewish descent it's been shown that they have a certain enzyme that might really affect the way they metabolize the statins and they lead to some increased side effects.

So for example, in my opinion, when I give the statin medications, I talk to patients that there are some side effects, but I will say, you might develop joint or muscle pain. They'll say, "Oh, I already have that, I already have that." I hear that a lot. I say, "OK, so good. Now you have to remember what your usual joint pain is and not attribute that to the medication. That's your typical musculoskeletal pain for whatever you're doing. Don't expect that to be any different necessarily when you're taking this medication."

So again, the bottom line for this study is it's important to know that this is real, and that to face it with your patients, to have the true discussion that, if you anticipate a bad outcome, you may be more likely to develop a bad outcome or side effect.

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