The nocebo effect of drugs

Abstract

While the placebo effect has been studied for a long time, much less is known about its negative counterpart, named the nocebo effect. However, it may be of particular importance because of its impact on the treatment outcomes and public health. We conducted a review on the nocebo effect using PubMed and other databases up to July 2014. The nocebo effect refers by definition to the induction or the worsening of symptoms induced by sham or active therapies. Examples are numerous and concerns both clinical trials and daily practice. The underlying mechanisms are, on one hand, psychological (conditioning and negative expectations) and, on the other hand, neurobiological (role of cholecystokinin, endogenous opioids and dopamine). Nocebo effects can modulate the outcome of a given therapy in a negative way, as do placebo effects in a positive way. The verbal and nonverbal communications of physicians contain numerous unintentional negative suggestions that may trigger a nocebo response. This raises the important issue of how physicians can at the same time obtain informed consent and minimize nocebo‐related risks. Every physician has to deal with this apparent contradiction between primum non nocere and to deliver truthful information about risks. Meticulous identification of patients at risk, information techniques such as positive framing, contextualized informed consent, and even noninformation, is valuable.

Prospective randomized study of sexual function in men taking dutasteride for the treatment of androgenetic alopecia

“…The inter‐site and inter‐study variability could be linked to the nocebo phenomenon, where occurrence of symptoms is related to a patient's negative expectations 11, 12. This phenomenon was shown in a randomized controlled study evaluating sexual dysfunction during treatment with finasteride for BPH.…”

Treatment Outcomes with Biosimilars: Be Aware of the Nocebo Effect

“…Perception gaps may be related to a nocebo effect that can lead to the induction or the worsening of symptoms induced by sham or active therapies [24,25]. When a nocebo effect is seen with an active therapy, this is a non-specific response in that the symptoms or physiologic changes cannot be explained on the basis of the known pharmacology of the drug and is not dose-dependent [11].…”

“…However, various strategies can be implemented in the clinic to help informed decision-making and negate the nocebo effect, including identifying patients at high risk, determining patient expectations of adverse events and providing reassurance if these are excessive, tailoring information to only provide pertinent details to the patient (Fig. 2) [7], reducing exposure of the patient to others experiencing side effects, and educating the patient on nocebo effects using case studies [25,39]. Physicians should consider implementing motivational interviewing techniques into the clinic by subtly guiding the patient to think about and verbally express their reasons for and against change, so that the patient is making an informed and considered choice, which is likely to help reduce the nocebo effect [40].…”

Placebo and nocebo phenomena from the perspective of evidence based and person centered medicine

“…Summaries of Product Characteristics (SPC) of drugs are silent about nocebo reactions to drugs what makes problems with informed consents. Nocebo phenomena distress patients, add to the burden of their illness, increase the cost of care, lead to non-adherence or discontinuation of otherwise an appropriate treatment, trigger prescription of additional drugs to treat unrecognized nocebo response [3]. Between 4% and 26% of patients in RCTs randomize to placebo arm discontinued the trial because of perceived adverse events [3].…”

“…Nocebo phenomena distress patients, add to the burden of their illness, increase the cost of care, lead to non-adherence or discontinuation of otherwise an appropriate treatment, trigger prescription of additional drugs to treat unrecognized nocebo response [3]. Between 4% and 26% of patients in RCTs randomize to placebo arm discontinued the trial because of perceived adverse events [3]. Clinical trials investigating the nocebo response induction are generally considered unethical because they harm.…”