The nocebo effect is the exact opposite of the placebo effect, whereby the belief that a drug will cause us harm ends up triggering negative symptoms. Photo / 123RF
From statins to Covid vaccines, researchers have discovered that many side effects are psychosomatic.
At the University of Liverpool, Dan Carr has spent the last few years trying to understand why some people experience side effects from statins, commonly prescribed medications that reduce the risk of heart attacks and strokes in susceptible individuals.
An estimated seven to eight million people in the UK take statins, according to the British Heart Foundation, but the drugs have developed a perceived association with a plethora of side effects ranging from muscle pain and weakness to digestive issues, sleep irregularities and headaches. Some research has suggested that around half of people taking statins experience these problems.
As a pharmacologist, Carr has been trying to get to the bottom of this. But like many researchers, he has found that the proportion of people who experience problems directly relating to the drugs should be relatively rare. There are certain gene variants that can cause statins to remain in the bloodstream for an unusually long time, but these are highly uncommon.
Last week a new study in the European Heart Journal added more evidence that statin intolerance is much less common than we think. Analysing data from more than four million individuals, one of the largest research endeavours ever carried out on the subject, it found that statin-induced side effects only occur in six to 10 per cent of people.
Instead, the study suggested that in the vast majority of cases, what appear to be statin-related issues are either background ailments that the person would be experiencing anyway, or psychosomatic.
Any medicine which has been subject to a certain amount of bad publicity can lead to something known as the nocebo effect. This is the exact opposite of the placebo effect, whereby the belief that a drug will cause us harm ends up triggering negative symptoms.
"The nocebo effect of statins is probably contributed to by the negative publicity and the fact that many of these supposed side effects are very subjective," says Carr. "Muscles aches and cramps can be due to a myriad of other reasons, particularly in older people, but can easily be attributed to statins. People also tend to have unfounded preconceptions about their risk of side effects. For example, one in three people believe they are allergic to penicillin, but only 10 per cent of that one in three actually are."
Over the past year, the nocebo effect and its impact on our responses to medical interventions has been highlighted by the wave of publicity surrounding the Covid-19 vaccines, particularly the intensity of media attention surrounding cases of adverse reactions.
Last month, psychologists at the Beth Israel Deaconess Medical Centre in Boston conducted a study that suggested that the nocebo effect may be behind a sizeable proportion of side effects following Covid-19 vaccination. As part of the study, 22,578 people were injected with a sterile solution which they believed to be a Covid-19 vaccine, with 35 per cent of them reporting symptoms of headache, fatigue and arm pain several hours later.
Robert Baloh, a professor of neurology at the University of California, Los Angeles, is an expert in the nocebo effect, which he dubs "placebo's evil twin".
"The nocebo effect is much more common than most people think, including doctors," he says. "It explains many of the side effects of drugs and vaccines, many cases of gluten sensitivity, environmental chemical sensitivity, electromagnetic sensitivity, and ultrasound sensitivity. People with negative perceptions of these things, through prior personal experiences and beliefs or suggestions from friends, family and the media, are more likely to focus and ruminate on routine body symptoms and then attribute the symptoms to an external source."
It is only in recent years that scientists have begun to fully appreciate the human propensity for subconsciously thinking ourselves unwell, and the frequency with which this occurs. Some estimates have suggested that up to 30 per cent of GP appointments may be with patients whose symptoms have a psychosomatic origin. Surveys have also found that up to a third of patients in an average general neurology clinic have symptoms that cannot be explained by any medical test or examination.
We now know that along with the nocebo effect, there are multiple different types of psychosomatic illness. One example is conversion disorder, where patients experience severe neurological symptoms such as paralysis or blindness which cannot be explained by medical evaluation. Another is health or illness anxiety where relatively innocuous symptoms become the subject of anxious thoughts, which then cause the symptoms to get worse.
All of these forms of psychosomatic problems can worsen with stress and declining mental health. Sophie Eastwood, a GP and clinical epidemiologist at University College London, says that it is important to recognise that while they may have a psychological origin, the physical symptoms very much exist.
"It's not so much a question of whether muscular aches or fatigue are genuine, if someone is experiencing them, they are certainly real," she says.
Because of nocebo, and the knowledge that talking about side effects leads to more side effects, doctors have even suggested giving patients far less information about the potential consequences of a drug or vaccine. However, psychologists believe that more openness is actually the best approach.
"I think it is important to explain the nocebo effect to patients before they receive a treatment," says Julia Haas, a psychologist at the Beth Israel Deaconess Medical Centre. "This includes informing them that many people experience symptoms even after placebo treatment and that these effects are probably caused by worries, negative expectations or misattribution of symptoms that may have occurred anyway. If patients know that not all symptoms they experience after treatment are necessarily caused by the drug, this can reduce their worries and maybe even the symptoms."
For other apparently psychosomatic conditions which specialists have been unable to explain through different tests and diagnostics, they can only really be untangled by addressing the psychological issues which are at the root of the problem.
Baloh recommends beginning with stress-reducing activities such as mindfulness, yoga and lifestyle interventions aimed at increasing exercise and improving sleep quality, as stress is often a key trigger for many of these symptoms.
But for more severe forms of psychosomatic illness, sometimes cognitive behavioural therapy or even more intensive neurological rehabilitation exercises are needed. One example is in the mysterious cases of so-called "Havana syndrome" which has affected CIA operatives all over the world over the past six years.
In December 2016, an undercover agent arrived at the US Embassy in Cuba complaining of acute pain and headaches, which he believed to be the result of a sonic or microwave weapon. As the news began to spread, more CIA agents and US Embassy employees all over the world started to report similar symptoms. But no such weapon has been identified, and no medical study has been able to identify any concrete biological origin for the symptoms.
In 2018, neuroscientists at the University of Central Florida put a patient with Havana Syndrome through an intensive week-long set of neurological rehabilitation exercises, from somatosensory stimulation – bursts of electrical stimuli delivered to the peripheral nerves in the skin – to stretching and balance training which can help relieve sensations of pain. After several days, the patient began to display improvements.
But for the majority of people who find themselves experiencing pain, fatigue or ailments which might have a psychosomatic origin, researchers advise that it is important to bear in mind that it is normal to experience harmless, short-term symptoms in our everyday lives.
As a young adult, Kerry Bexton suddenly began experiencing excruciating spasms of pain in her pelvis, but despite multiple scans and tests, specialists were unable to identify why this was occurring. Eventually she was referred to a psychologist who attributed it to sexual abuse she had suffered as a child.
"I was told that a lot of survivors of domestic and sexual abuse can go on to suffer with psychosomatic pain," she says.
"These can be repressed emotions and trauma that is not dealt with, and manifests itself in the body.
"I was placed on heavy morphine for over six years and told there was nothing else to be done."
Distressed at the prospect of needing to take heavy opioids for the rest of her life, Bexton began investigating various forms of psychotherapy which eventually led her to a treatment procedure called Rapid Pain Elimination Therapy.
This involves acceptance of the impact that thoughts and feelings can have on the physiology of the body, and forms of meditation to help process past trauma.
After a successful course of therapy, Bexton was inspired to train as a psychotherapist herself and has since set up a foundation to offer the therapy to others in need.
"It changed my life," she says. "Not a single drop of morphine has touched my lips since, and I'm now pain free."
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