Our brains can easily fool us.
No experienced doctor would deny the power of the placebo effect.
Today I want to discuss the nocebo effect, which occurs when negative expectations of something causes it to have a more negative effect than it otherwise would.
Drugs can exert a strong nocebo effect. If your brain thinks you will have a side effect, you may actually get that effect.
Nocebo brain trickery is relevant to statins. That’s why I used this wording in my last post: (Note the italics)
The actual frequency of muscle symptoms is hotly debated. Randomized controlled trials (in which patients donâ€™t know whether they are taking the statin or placebo) report very small increases in muscle complaintsâ€”about a 1-2% increase. Observational studies, however, reveal higher rates of statin muscle complaints–in the range of 10-20%.
The nocebo effect is also relevant to beta-blockers.
Beta-blockers, which are drugs that blunt the effect of adrenaline, carry enormous baggage about side effects. People think they will gain weight, be fatigued, or get short-winded when taking these drugs. Men think they will become impotent.
The evidence, however, does not support these perceptions. Similar to muscle complaints and statins, our brains may be tricking us.
An elegant study from a famous group of British researchers strongly suggests that most side effects from beta-blockers stem from the nocebo effect.
The authors did a systematic review of blinded trials that used beta-blockers in patients with congestive heart failure–a common reason to give beta-blockers. (The linked review is open access.)
They found, sit down for this, 28 of 33 classically described side-effects are not more common on beta-blockers than placebo. Table 3 and Figure 2 of the paper are eye-openers.
Side effects, such as, headache, impotence, weight gain, low blood pressure, shortness of breath were no more common with beta-blockers than placebo.
In fact, the side effect of depression, often attributed to beta-blockers, occurred less often in patients who took the real drug. Read that sentence again.
Some side effects were more common on beta-blockers. Dizziness, for example, occurred 3.7% more often in the beta-blocker arm. But the authors explain that a 3.7% increase actually means that of 100 patients who get dizzy on the beta-blocker, 81 of them would have had it on placebo.
The nocebo effect can also turn asymptomatic people with atrial fibrillation into symptomatic people with atrial fibrillation. I’ve seen the scenario many times. Here’s how it goes:
Mr Smith is in for routine follow-up. I note before going in the exam room that his ECG shows AF. Last year he was in sinus rhythm.
“How are you, Mr Smith?”
“I feel great.” I ask again…”Great? That’s a strong word.”
“Yea, doc, I have never felt better.” His wife confirms that he is active and vigorous.
But then the cheery confident demeanor turns sour when I tell him his ECG shows AF.
I spend the rest of the visit reassuring him that it doesn’t matter; he’s on anticoagulant already, his heart rate is controlled, the previous echo is normal.
No matter, weeks later, Mr. Smith is calling because he is fatigued and short-winded. And so begins the balance of treating AF symptoms without causing harm.
The authors of the beta-blocker side-effect paper boldly concluded that “clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect…”
I wonder. We clinicians have immense power with our words. I can’t quantify it, but the human brain surely controls a lot of our health.
P.S. I’ve written about the possible placebo/nocebo effect of AF ablation. Click on the link: Could Ablation for AF Be an Elaborate Placebo?