Jeremy Howick Ph.D.

Doctor You

Using Red Monkeys to Stop Nocebo-ing Ourselves

Research shows that negative thoughts can hospitalise

Posted Jul 31, 2019

Mr. A was a 26-year-old male who presented to an emergency department stating, “Help me, I took all my pills” and then collapsed. As he fell, he dropped an empty prescription bottle. The hospital doctors assessed and treatment him immediately. Mr. A was conscious but appeared drowsy and lethargic. He said that he had taken all of his medicine, which he said was a new drug for depression. The label confirmed that the bottle contained capsules to be taken as part of a clinical trial of an antidepressant drug but did not say whether the capsules were the active medication or placebo.

Mr. A was very fearful he would die of the overdose. He had received this bottle the previous day and had impulsively taken all of the remaining 29 capsules. He immediately felt that he had made a mistake and asked his neighbour to take him to the hospital.

Mr. A was pale with a blood pressure of 80/40 and heart rate of 110. He was shaking, and breathing rapidly. Examination was otherwise unremarkable. An intravenous line was inserted, blood drawn, and infusion of normal saline begun. All laboratory studies were within normal limits. After receiving 2 litres of normal saline, blood pressure rose but when they stopped the infusion the blood pressure dropped again. Over 4 hours, he was given 6 litres of fluid.

At this point, a physician from the clinical trial arrived and determined that Mr. A had taken placebos. When informed of this, Mr. A was surprised then almost tearful with relief. Within 15 minutes, he was fully alert, with normal blood pressure and heart rate.

That was a true story. How did the placebos cause Mr. A to have such a dramatic response? Basically, it was the ‘nocebo’ effect. The ‘nocebo’ is the naughty cousin of the placebo. Whereas the placebo effect is the effect of a positive expectation, the nocebo effect is the effect of a negative expectation.

How did the placebos cause Mr. A to have such a dramatic response? Basically, it was the ‘nocebo’ ...

What kind of hard evidence proves there is a nocebo effect?

The story of Mr. A is dramatic, yet it is an anecdote. To prove the existence of nocebo effects more generally, we need controlled studies. We did a mega study (a ‘systematic review’) and looked at what happened to over 250,000 patients who took placebo pills (like sugar pills) in clinical trials. Here's what we found:

  • 50 percent of patients reported some negative side effect (like pain or nausea but also more serious things).
  • 5 percent, or 1 in 20, dropped out of the trial because of a negative side effect.

This was relatively consistent no matter what kind of condition was being tested. But we can't infer from the fact that something bad happened to someone (like a headache) to the conclusion that it was because of the placebo pill. That mistaken inference is known as the post hoc ergo procter hoc fallacy. Let’s continue with the example of a headache. Someone might have had the headache whether or not they took a placebo in a trial. After all, people sign up for trials because they have a condition. And the condition might produce a headache. To check whether the headache was a nocebo effect (the effect of expecting something bad) or something that would have happened anyways, we dug deeper into our data. We found some trials that compared what happened to patients who took placebos with what happened to patients who didn’t take anything—for example they were on the waiting list. We found that patients who took placebos were more likely to have negative side effects than those who took nothing. By doing this we proved that nocebo effects are real, and not just the kind of thing that would have happened anyways.

How can we stop nocebo-ing ourselves?

...since the nocebo effect is basically the effect of a negative thought, then we are ‘nocebo-ing’ ourselves for three quarters of the day

I have not found an accurate estimate of the number of thoughts average humans have every day, but it is almost certainly in the tens of thousands. A problem is that, according to Dr. Raj Raghunathan, three quarters of these thoughts are negative. Most of the negative thoughts are related to feelings of inferiority ('How come I can't have what the neighbour has?' or 'How come I am the only one who is not taken?') or control seeking ('Why doesn't the world change to meet my expectations?') Ruminating about these thoughts makes us feel bad and also increases the risk of mental illness. Worse, since the nocebo effect is basically the effect of a negative thought, then we are ‘nocebo-ing’ ourselves for three quarters of the day.

How to stop nocebo-ing ourselves

Fortunately there are a lot of ways. Many psychological therapies focus on challenging the negative beliefs. For example, thoughts of inferiority can be challenged by noting that there is always someone better off, and also someone worse off, and that is okay. The two I use are:

1. Meditation. The effect of meditation is to calm the mind, the same way waves caused by a pebble dropping in a flat lake fade away. Once the mind is calmed, people almost invariably find that things are pretty good after all. There are 100s of ways to meditate, and many only take a few minutes. Here are some you can try: ‘I am loved’, ‘I am worthy’, ‘I am confident’, 'Today is the best day of the year.'

Public domain pictures (.net)
Fading waves
Source: Public domain pictures (.net)

2. Don’t think about a red monkey. Just by reading that phrase, the vast majority of you will have conjured the image of a red monkey. The thought of the red monkey, at least for a moment, distracted you from anything else you were thinking about. This shows that you can replace negative thoughts with more productive ones. Repeating positive affirmations (‘I am loved’, ‘I am worthy’, ‘I am confident’, 'Today is the best day of the year') continuously will drown out the negative stuff. If you are familiar with mantras or prayer, these can have an event more powerful effect (more on those in a future post). Affirmations work best when combined with meditation.

Most of us don’t nocebo ourselves so badly that we end up in the hospital like Mr. A. But negative thoughts can dampen our moods, make us less fun to be around, and contribute to ill health. Meditating and thinking about red monkeys can help.

References

Reeves RR, Ladner ME, Hart RH, Burke RS. Nocebo effects with antidepressant clinical drug trial placebos. Gen Hosp Psychiatry. 2007 May-Jun;29(3):275-7.

Jeremy Howick, Rebecca Webster, Nigel Kirby & Kerry Hood. Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Trials volume 19, Article number: 674 (2018)