The nocebo effectThe nocebo effect is the negative counterpart of the placebo effect. He describes undesirable side effects of a sham treatment – when it does not heal, but aggravates or causes complaints in the first place.
By Franziska Badenschier
Suicide with a placebo? A 26-year-old American is severely depressed. Then his girlfriend leaves him too. He wants to take his own life, swallows 29 capsules he was given the day before because he is participating in a study on antidepressants.
Shortly afterwards, he shakes, breathes heavily, his blood prere drops rapidly – he regrets the overdose and has a neighbor drive him to an emergency room.
"Help me, I've taken all my pills", he says, then he collapses. After a few hours, the doctors find out: Your patient belongs to the group of study participants who received a placebo – a dummy drug without an active ingredient. When the patient hears about it, his symptoms disappear within a quarter of an hour.
A harmless drug with harmful side effects; a placebo that does not heal, but aggravates complaints and supposedly makes people ill: that is the nocebo effect.
Nocebo "I will hurt
Nocebo is Latin for "I will harm". The positive counterpart is placebo: "I will heal". In the placebo effect, a sick person is given a preparation for appearances, without an active ingredient, and yet the patient feels better afterwards – because the person expects the therapy to work. Or because the doctor or nurse took their time. Sometimes more attention alone can alleviate discomfort. Or because the symptoms would have disappeared all by themselves at that point – regardless of whether they were treated with the drug or not.
The nocebo effect is therefore also called the "brother of the placebo effect" referred to as "the dark side of the imagination".
The term nocebo has only been used for a few years. But the phenomenon has been known for much longer. And not so much from medicine as in an anthropological context, especially from voodoo.
So there are reports from the beginning of the 20th century. There is a nineteenth-century story about someone who thought he was going to die because someone else pointed a bone at him. Although the doomed subject was healthy-with no pain, fever, or other symptoms-the subject felt weak and dying.
Negative thoughts can cause side effects
Anxious people more likely to be affected by the nocebo effect
Something that isn't really there makes you sick: that's the nocebo effect in the strict, original sense of the word. In the meantime, however, the term is used more broadly: A nocebo effect is also when a patient uses a drug that actually contains an active ingredient and, as a result, symptoms worsen or undesirable side effects occur – against all odds.
After all, it goes without saying that not every drug works for everyone and that there are undesirable side effects.
However, when a patient's pessimistic or fearful attitude is responsible for the poor therapeutic outcome, this is known as the nocebo phenomenon. Many anecdotes and figures can be found in the specialist literature.
Some examples of the nocebo phenomenon:
– A librarian has to go to the hospital every now and then because she has had a narrowing of a heart valve since childhood. Once, the head physician stops by during his rounds and tells his team that this is a classic case of "TS" is. The woman believes "TS stands for "terminal situation, according to which she is about to die. She soon can hardly breathe, fluid collects in her lungs. Even a resident couldn't convince her, though he explained: TS is short for tricuspid valve stenosis, the technical term for her condition. The alarmed chief physician returns to the patient a few hours later to explain the misunderstanding to her in person – but she is already dead, dead of water lung. – At the Eppendorf University Hospital in Hamburg, several test subjects were inflicted with pain using a hot plate. In one run, the subjects were given a painkiller. That's what they were told – and most of the test subjects said they felt hardly any pain at all. In another run, patients were also given the same amount of painkiller, but told it was saline without any effect – whereupon the pain was almost as bad as in another run without any painkiller at all. – And some studies have already proven this: Those who study the package insert of a drug in detail or are informed in detail by the doctor or pharmacist about side effects are also more likely to suffer from these consequences, even if they are only annoying and harmless.
Still unclear: exactly how the nocebo phenomenon arises
Unintended negative suggestion or self-fulfilling prophecy: this is how experts explain the nocebo effect, among other things. Doctors and researchers do not yet know exactly what goes on in the body during this process.
However, the experts do have a few explanations for the nocebo phenomenon. One idea is: A patient is given a drug. Expect side effects or that symptoms will worsen.
These negative expectations lower the level of endorphins – and less of these so-called happy hormones in the blood can actually make the patient feel worse and be more sensitive to pain.
At the same time, when the body expects something negative, it sometimes releases the neurotransmitter cholecystokinin. This is a hormone that acts as a neurotransmitter in the brain and may be involved when a feeling of anxiety or panic develops.
In addition, studies using brain scans have shown: Pain-processing brain regions are activated – as if the brain senses pain even when no pain receptors have been irritated.
Nocebo studies would be ethically questionable
And even with sick patients, nocebo research is ethically questionable, said German placebo and nocebo researcher Paul Enck, for example: "You can't make a patient's symptoms worse by saying, on a trial basis, 'This medicine doesn't help you, it makes your symptoms worse.'"
Neuroscientific studies in particular are still lacking. Brain scans and co. could help to explain the nocebo effect.
And conversely, the nocebo effect could help neuroscientists with other research questions: After all, the nocebo effect is a stress factor and thus well suited, for example, to track down the neurobiology of fear.
The neurobiology of the nocebo effect is still being researched
What to do about the nocebo effect?
Nocebo effects should be avoided, demands the Competence Network Placebo, to which Paul Enck also belongs. To do this, medical staff would first have to develop more awareness of the nocebo effect – in practices and hospitals, pharmacies and naturopathic centers.
Sayings such as "We'll put you to sleep; it'll be over in a moment", can be meant to be funny, but can be misunderstood – especially by anxious people or by patients in extreme situations such as shortly before an operation.
So to avoid the nocebo effect, doctor-patient communication should use some rhetorical skill: Instead of saying "Five percent of patients cannot tolerate this medication", it is better to say: "95 percent tolerate this drug very well".
It also makes sense to emphasize the benefits of a drug or therapy rather than explain any side effects that may occur.
Doctors can even ask their patients if they even want to be told about any side effect, no matter how unlikely. Or they explain to patients what the information on the package insert means: "Very rare" for example, according to an international convention, "at most one affected person under 10.000 using the product".
Good doctor-patient communication prevents nocebo
Ethical dilemma for doctors
If patients do report one or the other adverse side effect, then both patient and physician should ask themselves: Are the complaints a symptom of the disease?? Or a symptom of another condition that may not yet have been diagnosed?
An actual side effect of the drug? Or just a coincidental disturbance of well-being, because something else is bothering the patient? Or is it perhaps actually a nocebo phenomenon??
If the complaints are due to the nocebo effect, then the doctor can react in different ways: for example, by explaining how the advantages outweigh the disadvantages. Or he may prescribe a different medication, but one that contains the same active ingredient. Or he discontinues the drug altogether.
Sometimes anxiety-relieving medications can be prescribed to alleviate the fear of the medication that is actually needed or its consequences.
Physicians, in any case, are in a dilemma: on the one hand, they are legally obligated to inform their patients about all contingencies of treatments and medications. On the other hand, they should be guided by the ancient principle "primum non nocere", in German "zuallererst einmal nicht schaden".