‘Nocebo’ Response Should be Considered in Doctor-Patient Communication

Nocebo Response

When it comes to pain medication, what you know might hurt you. Research on the nocebo effect 1 suggests that patients who are educated about the potential risks or non-efficacy of the pain drugs they take are at higher risk for developing negative symptoms and less satisfied with the outcome after taking the drug.

The nocebo effect, like the placebo effect, is the product of a patient’s suggestibility and expectation. Placebo effect studies have demonstrated that when a patient is conditioned to expect a positive outcome, he is more likely to experience a positive outcome. This is true of the nocebo effect, as well. A patient who is conditioned to anticipate a negative reaction to or inefficacy of pain medication is much more likely to experience the inefficacy or negative physical, physiological, behavioral, or functional response to medication. Patients conditioned to expect that their pain medication will not work receive less pain relief from their pain medications.

Three Types of Nocebo Effects


  • The positive effects of the pain medication are reduced by the patient’s negative expectation.
  • Patients whose expectations are not met by pain treatment once may have lowered expectation when it comes to the medicine’s efficacy in future treatments and experience less pain relief as a result.
  • Patients whose expectations have been preconditioned and lowered by negative information as to a drug’s efficacy may lose the benefits of the placebo effect, which have been identified as a relevant component of medicinal relief. In other words, believing a medication or procedure is going to improve your pain is an important part of pain relief.

Clinical Trials

During randomized controlled clinical trials, patients were more likely to experience adverse events or pain after being informed of the potential they might occur. Patients who were told they might experience a negative drug effect were more likely to experience the effect, even when the effect was in opposition to the pharmacology of the drug. Disclosing potential serious illnesses—including cancer— associated with a drug was more likely to induce a negative prognosis.

Though the placebo response has been widely studied and verified, the nocebo response remains somewhat of a mystery. Studies of the neurobiology of drug action indicate a similar effect between the molecular changes involved in drug treatment and placebo responses. To date, no such effect has been studied in the case of nocebo effect.

Effects of Doctor-Patient Communication

A recent (2017) review seeks to identify doctor-patient communications that may trigger nocebo reactions and suggests clinicians avoid potential negative outcomes by down-playing negative information and emphasizing positive outcome expectations when counseling patients.

In one study, almost half of the 15 patients who were told their drug might produce headaches developed headaches during the trial. None of the 13 patients in a separate group that was not given the headache information developed headaches. Being told to expect a headache might have produced the headaches, so the authors of the study concluded it was best not to mention the possibility of headaches to patients being prescribed drugs with the potential side-effect.

In a randomized controlled study of epidural procedures, patients who were forewarned to expect a prick of pain were more likely to experience discomfort than patients who were told the medication would make them comfortable during labor. Researchers concluded that framing the experience in a more positive light was beneficial to the patients’ experience.

In another study, patients undergoing prostate surgery were more likely to develop negative side effects over time if they were told in advance they might occur. Roughly 43 percent of a group of patients who had been told about potential negative sexual side effects later developed those side effects, while only 15 percent of those in the group who were not informed of the side effects developed them.

The nocebo effect also discourages potential study subjects from participating in research. When the subjects were informed of the potential negative effects of participating in the study, they were more likely to drop out of the group. Study subjects who were informed about potential gastrointestinal consequences were more 6 times more likely to experience gastrointestinal side effects and drop out of the study prior to its conclusion.


Practitioners and researchers should carefully weigh the benefits of informing patients of potential negative effects of medication or procedures against the possibility of inducing the nocebo effect, along with its potential harm. This may be particularly true in cases of pain treatment, as patients who suffer from long-term, chronic pain may be more susceptible to the negative events associated with the nocebo effect. Because the expectation of increased pain can trigger or increase extent anxiety or depression, which may then contribute to further algesia and hyperalgesia and inhibit or produce interactions within the neuropathways that lesson a medication’s effectiveness (or placebo benefits), the nocebo effect should be an important consideration prior to pain-medication counseling.

Concern should also be taken with patients whose health depends upon the medications being prescribed. In one study, breast cancer patients counseled as to the potential negative effects of adjuvant endocrine treatment were more likely to experience long-term side-effects and be less compliant in continuing their treatments.

Studies have shown that a positive doctor-patient experience is more conducive than a negative experience in producing positive long-term health results. The amount, delivery method, and attitude of doctor-patient communications can contribute to placebo or nocebo experiences in patients and should be carefully balanced to minimize negative suggestions and emphasize positive outcome expectations.

  1. Nocebo effects in clinical studies: hints for pain therapy
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