Nocebo: The Power of Negative Thinking?

Doctors Need to Appreciate the Effects of Prescribing and Describing Therapy

Maybe it's the power of marketing. Maybe it's faith in our doctors. Or maybe the physical effects of what we believe are more powerful than we like to think. In any event, new data indicate that how doctors describe what they give us may effect us in powerfully positive or negative ways.

It's a Sham
Placebos, and their lesser known counterparts nocebos, are sham treatments. The difference is in the response to the therapy. Placebo, from Latin meaning “I will please” is often delivered in a manner that leads the patient to expect a positive effect. Nocebo, meaning “I will harm,” is associated with negative responses to inactive therapy.

In a study reported today (http://bit.ly/gec3tz), people's pain levels fluctuated greatly based on what they were told about a pain medicine they had been given, including an increase in pain when told they were no longer being given the drug – when in fact they were still receiving it. (The nocebo effect.) So, patient belief was a strong indicator of whether the drug worked or not, even though the dose of the drug did not change throughout the experiment.

Nocebo effects can be enhanced, too, with warnings the therapy will likely produce negative effects. In other words, a placebo “sugar pill” is given to patients who are led to believe that the pill will provide pain relief; the nocebo effect is enhanced with a warning that the pill will likely cause adverse effects, such as nausea.

However, the doctor does not have to say anything for the nocebo effect to kick in. Patient beliefs may be established long before he or she shows up at a doctor's office. In Science Translational Medicine, researchers suggest that doctors may need to consider dealing with patients' beliefs about the effectiveness of any treatment, as well as determining which drug might be the best for that patient. For example, people with chronic pain will often have seen many doctors and tried many drugs that haven't worked for them. Professor Irene Tracey at Oxford University, said, “They come to see the clinician with all this negative experience, not expecting to receive anything that will work for them. Doctors have almost got to work on that first before any drug will have an effect on their pain.”

All science needs a mechanism of some kind, so what is behind these powerful placebo and nocebo effects? It’s not clear, but the evidence does suggest that it’s not all psychological. Physiologically, there appears to be an endorphin release in the brain that accompanies a placebo response. Placebos given to people who are told they are pain killers will actually elicit analgesic effects via both drug-related (neuropharmacological) and neurologic (neuroanatomical) avenues. In other words, the body’s response is similar to what one would expect from actual medicine despite the fact that the sugar pill given contains no medication.

Additionally, placebos commonly elicit beneficial therapeutic responses in anxiety and depressive disorders. The psychological behaviorism theory considers the placebo a stimulus conditioned to elicit a positive emotional response. Some research suggests that pain sensitivity and pain anxiety increase susceptibility to placebo effects.

Stunning Effects
While not as commonly known as placebos, nocebo effects can be stunning. For example, in one study, patients were told they were receiving either a relaxant, a stimulant, or an inactive agent; in point of fact, all patients received the inactive agent. Patients told they were getting a relaxant showed reduced stress levels, while those who thought they were getting a stimulant showed increased arousal levels.

With the heart pain known as angina, for example, sham surgeries work in up to 70% to 80% of patients who show clinical improvement great enough to increase the key measures of heart function (known as functional class). Similar data are also are seen in heart failure patients who show improvement in functional class or, at the very least, significant improvement in quality of life.

Placebo drug therapy isn’t quite as “effective” as that sham surgery was, but it still is quite common. In a study by Italian investigators, 600 patients with histories of drug side effects were given inactive placebos and more than 1 in 4 showed “drug” side effects. The nocebo response was significantly higher in women than in men. So, the nocebo effect occurs frequently in clinical practice. In clinical trials, too; it’s rare that a placebo will elicit significantly more side effects than the comparison drug therapy, but it is not uncommon that in sheer numbers more stomach upset is reported with the placebo, despite the fact there should be NOTHING in the inert agent to cause stomach upset.

By the way, even mechanical devices can show placebo/nocebo effects. In a study called VPS II, pacemakers were implanted in patients but only half were activated; the rest were in monitoring mode and collecting information but not actually pacing the heart. Despite the fact half were turned off, both groups showed similar improvements.

Finally, it’s not just the words and manner of the doctor that can influence the effects of placebos. Evidence suggests you can literally build a better placebo by taking into account size, color, shape, and “brand” of the sugar pill!

With doctors using more and more technology while spending less and less time with patients, it’s important that doctors appreciate the power of prescribing and describing a therapy – whether it’s a real therapy or a perceived therapy.