Nocebo: The Evil Brother of the Placebo

4. October 2012

Using words, doctors cannot only heal and relieve pain, but also increase the intensity of pain. As part of their review, physicians examined which phrases used by doctors brought consternation to their patients and were able to cause them harm.

The downside of the Placebo Effect (placebo, latin: “I will be appreciated”), the Nocebo Effect (nocebo, latin: “I will harm”) only recently became the focus of fundamental science and clinical medicine. A search of the database PubMed on 4 September 2012 revealed 178 entries on “nocebo” compared with 157,120 references to “placebo”. For their article on the neurobiological mechanisms of the Nocebo Effect, physicians Winfried Hauser, Emil Hansen (University Hospital Regensburg) and Paul Enck (University Hospital of Tübingen) searched through PubMed using the search terms “nocebo” or “nocebo effect” looking for works that were published between 1960 and December 2011.

Definition and experimental nocebo studies

The term “nocebo” was originally used in order to designate the negative counterpart to Placebo Effect and distinguish the unwanted from the desired effects of a placebo (dummy treatment or dummy intervention). Today, both terms are used in a broader sense: Non-specific effects of a medical treatment are defined as Placebo Effects if they are useful, and as Nocebo Effects if they are malicious. Nocebo Effect refers to symptoms and symptom exacerbations that arise under a dummy treatment and/or by deliberate or inadvertent suggestion and/or negative expectations.

Doctors are often complicit themselves, explains psychosomatic medicine expert Professor Paul Enck to “Bild der Wissenschaft”. He criticises the “recklessly mentioned matters in diagnostic discussions” which are uttered by many physicians. Medical conditions are defined as Nocebo Response when induced via negative expectations of the patient and/or unintended negative suggestions from the doctor in the absence of a (pseudo-) treatment. From the studies it comes out that nocebo reactions are acquired via all kinds of learning paths. From the reverse perspective, it must be assumed that such reactions, when they occur in everyday clinical practice, have been acquired both by expectations as well as by learning during the patient’s past.

Finding the right words

Medical communication and the patient’s expectations of therapy can have both significant positive and negative effects on the course of medical treatment. “In medicine, one starts with the assumption that fear and pain are reduced when a painful manipulation is announced in advance and one expresses compassion after this pain has been experienced”, says Winfried Häuser from Klinikum Saarbrücken and the Clinic for Psychosomatic Medicine and Psychotherapy, Technical University of Munich. A study of radiological biopsies showed that patient’s fears and pains were amplified when the actual description of the measures involved use of negative words like “prick”, “burn”, “hurt”, “bad” or “pain”.

In another study, a local anesthesia for pregnant women was announced in one case with the following words: “We will now administer a local anesthetic, which makes the area numb, so that an epidural-spinal anesthesia can be performed, so that it will be comfortable for you”. The second group received the following words: “You will now feel a pang and a burning sensation at the back, as though you have been stung by a bee, that’s the worst part of the whole procedure”. Pain sensations among pregnant women in the second group were significantly higher (median, 5 versus 3 in pain intensity on an 11-point scale). “The awareness of the possible complications of therapy and negative expectations of the patients increased the incidence of adverse effects”, emphasises Häuser.

The physicians find themselves in an ethical dilemma: on the one hand, they are obliged to inform their patients about the treatment and its potential side effects, on the other hand it is up to the doctor to minimise the risks of a medical procedure for the patient, including the risks coming from explanations. The studies cited above show however that nocebo responses can be induced by negative suggestions in explanatory discussions. Patients are, considering this, particularly highly susceptible in existentially threatening situations, such as cases involving an operation because of an acute, serious illness or an accident.

Strategies to solve the doctors’ dilemma

The medical team under Winfried Häuser recommends the following strategies to reduce the dilemma:

  • Focus on tolerance in the explanatory discussion: information on the frequency of possible side effects can be formulated positively (“Most patients tolerate the actions very well”) or negatively (“5% of patients report […] side effects”). A study of educational strategies for influenza vaccination shows that those vaccinated show fewer side effects after vaccination when the number of persons who tolerate the vaccination well are mentioned in the informed consent discussion than those people to whom the numbers of persons with adverse reactions to vaccination are reported.
  • With the “allowed silence” approach, the patient is asked before prescribing the medication whether he or she agrees to not acquire any information about mild and/or transient side effects. With serious and/or irreversible side effects, the patient must be informed.
  • Patient education: a systematic review (4 studies, 400 patients) showed that the training of patients with chronic pain via a pharmacist – for example in the form of general information about medicated and non-medicated pain management – reduced the number of adverse effects of drugs from 4.6 to 1.6.
  • Communication training using actor-patients or role playing in medical studies provides the ability to use the power of words of the doctor in a targeted and specifically helpful way for the patient. “The ability to give positive suggestions and to avoid negative ones should be increasingly considered in nursing education”, recommends Häuser.

Nocebo Effect with medications

The Nocebo Effect in relation to side effects of medicines may be especially widespread, scientists suspect. If a patient is informed about the potential side effects upon administration of an agent, a certain number of subjects develop these same symptoms even if the preparation received is a sugar preparation without any of the agent. The cost of these Nocebo Effects with drugs in Germany alone, according to experts’ estimates, amounts to two to three billion dollars a year.

Unintended negative suggestions in clinical practice

Examples on the topic: “What doctors should rather not say” collected by Häuser among colleagues at a medical conference:

  • Triggering of uncertainty:
    “Maybe this medication will help.”
    “Let’s try out this remedy now.”
    “Try to take your medicine regularly”.
  • Specialist jargon:
    “We will wire you up now”. (connecting to the monitor)
    “Then we cut you into many thin slices”. (Magnetic Resonance Imaging)
    “We are now attaching you to the artificial nose [literal German translation for ventilatory support using face mask]”.
    “We were looking for metastasis – the results were negative”.
  • Ambiguous words:
    “Then we’ll finish you off)”. (Preparation for surgery)
    “Now we’ll put you to sleep, soon everything will be all over”. (Induction)
    “I’ll quickly get a little more from the chemical cabinet/ anesthetic safe [German: Giftschrank, literally meaning “poison chest”], then we can begin”.
  • Negative suggestions:
    “You are a patient at risk”.
    “It always hurts like hell”.
    “You should not lift anything heavy any more. Don’t, so that you won’t end up paralysed as well”.
    “Your spinal canal is sharply restricted. The spinal cord is being squeezed”.
  • Focusing of attention:
    “Are you unwell?” (PACU)
    “Let us know if you have pain.” (PACU)
  • Ineffectiveness of denials and diminishment:
    “You need have no fear”.
    “It’s bleeding a little bit now”.
30 rating(s) (4.6 ø)


Interesting approach to the patients reaction on the information we are giving in clinical practice. It emphasizes the dilemma between full information on a scientific basis and a more patient-oriented, less complete information.
Human or legal information?

#5 |
pharmacist james snowdon
pharmacist james snowdon

A terrific timely article! As a teacher of pharmacy students, I am constantly haranguing them about the significance of the words that the students say to their patients. It seems that the nocebo vocabulary is their natural first choice to use and they seem to unaware of its affect on the patients they treat. This article will be on the student mandatory reading list.

#4 |
MR. Mumin Sadiku
MR. Mumin Sadiku

Dear DocCheck eny time is useful to have more knolidge in Medicine because you feel more secure and have big Seelfesteem.

#3 |
Dr. John Bond
Dr. John Bond

I agree, very interesting, with some very good point points about how some simple words can really invoke a great deal of anxiety in patients – I really enjoyed the examples, very witty, but also very illuminating!

#2 |
Industry employee

Interesting article!

#1 |

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