Nocebo Response

By Malcolm P. Berger, M.D.

Wednesday, October 20, 2004



The nocebo response, also known as the negative placebo response, is the development of nonspecific side effects from an inert substance. It is the opposite of the placebo response. Some of the side effects experienced from medications are actually nocebo responses.  While some authors place voodoo curses in the nocebo category, experiencing negative when negative is intended is more of a placebo response.  The nocebo response is the contrary response.  Since in medicine we try to help, it is the inexplicable downside of treatment.  Most, but not all, nocebo responses are subjective (sleepy, dizzy, confused, headache, staggery, GI upset, pain, etc.).  Some are worsening of symptoms for which treatment is given.    Nocebo responses are often used to direct care away from or towards a specific treatment.  Nocebo responses are common among drug seekers, who profess unusual and debilitating side effects from non-narcotic treatments and among self-directing patients.  Frequently, these patients will ask relatives or friends, or check on the internet, decide what they want (or don't want) and then have "horrible" problems from any treatment that doesn't fit their understanding of what they should be taking.  Typically, a treatment will make the condition worse or produce intolerable side effects.

In addition to the direct nocebo response, there is nocebo by proxy, in which family members report nocebo responses in persons who don't speak for themselves.  Nocebo-by-proxy follows the same direction as the nocebo response, but is much more difficult to deal with, since the patient's representative has an agenda that includes lack of trust in the health care provider. 


Nocebo response might be blocked by benzodiazepines?

Benzodiazepines 1995 PCT

Lorazepam and alprazolam may mitigate the negative placebo response when there are anxiety and depressive features.

Nocebo 1997

Compensation neurosis

Nocebo 1998

Due to change in medications, not the medication; anxiety, phobia and somatization, with somatization being the most common element of the nocebo response.

Nocebo 2004 RCT

27% of patients in this study suffered from significant nocebo response

nocebo effect

A brief review of nocebo effect; not from medline, but some studies showing the power of this concept

Nocebo effect 2002

Due to anxiety, depression, somatization, situational and contextual factors.

Nocebo strategy 2002 RCT

Placebo given. If untoward response, second placebo. If still untoward response, no active agent. If no nocebo response to first placebo, give 1/10 of active drug and increase slowly.

Proglumide 1997 RCT

Blocked the nocebo effect with a cholecystokinin antagonist

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