Side-effects could be all in the mind

A study earlier this year revealed men are worse than women at remembering to complete tasks. Picture: AFP

A study earlier this year revealed men are worse than women at remembering to complete tasks. Picture: AFP

Published Feb 25, 2014

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London - We’ve all heard of the placebo effect — where the power of the mind causes patients to feel that a treatment has improved their symptoms — even though the “treatment” may be nothing more than a sugar pill.

In many clinical trials, patients have reported miraculous results from taking a placebo they believed was the real thing.

Now it has been shown that this phenomenon is so powerful people can have a “nocebo” effect: where they are so convinced a drug is working that they start having imagined side-effects.

Experts say this suggests some of the side-effects we feel from medication could be all in the mind — you really can worry yourself sick.

A recent study in the journal Psychiatry Research assessed 21 clinical trials and studies that tested a treatment for depression against a placebo. Incredibly, it found that nearly half of patients given harmless sugar pills had side-effects as intense as those who took the real thing.

Among people in placebo groups, 44.7 percent reported having an adverse side-effect, such as pain, itching and changes in heart rate, and for 4.5 percent these were so bad they dropped out of the trial. By comparison, in the groups having the real medication, 40.9 percent reported side-effects and 6.8 percent dropped out.

The neurologist, Dr Dimos Mitsikostas, who led the study at Athens University and other centres, said the findings could prove important in improving the rate at which patients adhere to their medication regimens.

“Almost one out of 20 placebo-treated patients discontinued treatment due to adverse effects. Nocebo, therefore, deserves much attention in the context of clinical trial design and in clinical practice as well,” he says.

The nocebo phenomenon has been highlighted in other studies, including one paper on migraines published in the journal Pain in 2009. The paper reviewed every placebo-controlled trial conducted on a migraine drug and found side-effects were common among those given the sham treatment.

Indeed, the patients suffered the effects of whatever drug they thought they were having — those who thought they were having painkillers, for example, reported experiencing digestive problems.

Meanwhile, a 2013 study by doctors at St Mary’s Hospital, London, found that most adverse side-effects attributed to beta blockers are down to nocebo. The team looked at 13 trials of beta blockers as a treatment for heart failure, and found that of 33 side-effects associated with the drugs, only five were significantly more common in people on beta blockers than those taking a placebo.

“The majority of adverse effects reported with beta blockers in heart failure are not caused by the beta blockers but arise either from the disease itself, another coincidental problem, or from the power of suggestion — the nocebo phenomenon,” the team reported.

Nocebo raises ethical questions, as it can cause real harm. Experts say patients who are anxious and stressed are more likely to suffer the nocebo effect — anxiety activates the hormone cholecystokinin, which carries messages between nerve cells and may increase the perception of pain.

Studies have also found nocebo is more likely to happen when patients are asked specifically about adverse effects, or read about the side-effects on drug packaging or online. Here nocebo rates can rise to more than 70 percent.

The problem can also be triggered by the manner and behaviour of the doctor prescribing the treatment.

Some research has shown that a cold, disinterested and emotionless doctor raises the risk of a nocebo response because patients may be more anxious and less confident. David Blake, emeritus professor of rheumatology at Bath University, says research on nocebo shows how crucial it is for doctors to discuss side-effects with patients when prescribing medication but then to reassure them.

“Nocebos appear to heighten our sensitivity to internal bodily stimuli, such as an itch or tummy gripe,” he says. “Put it all together and you get a high incidence of reported side-effects from a placebo medication that causes none. This harms people.

“A good doctor will raise awareness of these issues at the onset of drug treatment and at review.”

Professor Cary Cooper, professor of psychology at Lancaster University, adds: “What is particularly interesting from this new research is the sheer scale of the effects. And it will not only apply to treatments used in a clinical trials — when a GP prescribes a therapy for a patient, that too could result in a nocebo effect.

“It may even be seen with over-the-counter drugs. It is such a powerful phenomenon that we should be looking at ways to harness it for the good of patients.”

Dr Felicity Bishop, lecturer in health psychology at Southampton University, adds: “This study confirms that nocebo effects have the power to harm some patients. Our research has shown information leaflets for clinical trials often fail to tell patients that even if they get the placebo they might experience adverse side-effects.

“Placebo and nocebo effects have been overlooked for too long and treated as nuisance factors to be controlled for. It is time to find ways to harness placebo effects and minimise nocebo effects in routine medical care, and that is what we are working on here.” - Daily Mail

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