Lexique

Defining Nocebo

Defining Nocebo

Etymology

The effect caused by the entry of an inert substance is not always beneficial, that is not cause by placebo effect. It can be damaging to the individual, it is the nocebo (Latin for “I will harm”).

Definition

“In clinical trials, a number of patients in placebo suffer from side effects similar to those of the tested treatment” (Colloca and Miller, 2011).

Various evidence of the nocebo effect

A verbal suggestion is enough to produce a nocebo effect following administration of an inert material. Study shows from the experience of different medical suggestions based on an electrical signal or tactile contact supposed to be more or less painful. The tested healthy subjects have transformed this warning in pain, and pain of low intensity became high intensity (Colloca et al., 2008). Specialists call this consequence the hyperalgesia understood as an increase in pain perception without a measure with stimulation (Benedetti et al., 2011).

The nocebo effect can also reproduce the real treatment side effects, by a kind of mimicry. The patient knows that he is taking medication and unconsciously recreating the undesirable effects which he has heard from relatives that he heard in the media or has played on the record. 20-30% of healthy subjects involved in such experiences feel headache, drowsiness or nausea. A study shows that healthy people are being made to inject Remifentanil complain of leg pain under the influence of the nocebo effect (Bingel et al., 2011). The mere announcement of a class of drug can produce a nocebo effect. Indeed, a meta-analysis tests the effectiveness of antidepressant treatments (Rief et al., 2009). It compares the nocebo effect of two placebos, a tricyclic and SSRI. Patients receiving tricyclic placebo had more symptoms than those taking a placebo SSRI for dry mouth (19.2% / 1.2%), vision problems (6.9% / 1.2% ), fatigue (17.3% / 5.5%), and constipation (10.7% / 4.2%). Information on drug category is already likely to influence the patient.

Mechanisms

As in the placebo effect, but reversely, the sense of expectation can produce negative consequences such as increased pain. This amplification comes from various brain regions such as the anterior cingulate cortex, prefrontal cortex, the insula and hippocampus (Koyama et al, 2005; Hsieh et al, 1999; Ploghaus et al, 2001; Sawamoto et al, 2000; Porro et al , 2002; Lorenz et al, 2005). The dopaminergic and opioid systems also act together in the nucleus accumbens being disabled (Benedetti et al., 2011).

Trust and distrust in the relationship caregiver / patient

A poorly worded set is sufficient to trigger a nocebo effect. Anesthetists have compared the sensation of pain felt during the injection of an anesthetic in pregnant women. The nocebo group was prepared to sting a current set “you will feel like an intense bee sting. This is the most unpleasant part of the procedure. ” The placebo group was informed differently, “we will give you a local anesthetic to numb you so that you feel comfortable during the operation.” The study shows that the use of more soothing words had a significant impact on the pain sensation and degree of discomfort during surgery (Varelmann et al., 2010).

Stress, nocebo and complications

Stress potentiates the nocebo effect. In a study on the influence of prayer on healing patients and treated for a heart disease, a randomized controlled trial shows that the group of patients who were informed that prayers were said for them had more complications than patients not being informed (Benson et al., 2006). One hypothesis is that the added stress induce a nocebo effect and / or would cause increased risk of complications. More recent studies show the involvement of the dopaminergic system like the placebo effect (Benedetti et al., 2011).

The nocebo effect in non-drug interventions

Nocebos of effects can occur following the prescription of a non-drug intervention. But alas, few studies exist on the subject, particularly in a preventive rather than therapeutic, but perspective.


What it means for Patients

Prescription medicine can cause nocebo effect. A doctor trust is fundamental to prevent it.

What it means for Health Professionals

Improper formulation of a deposit on the effect of a treatment or a non-drug intervention can trigger a nocebo effect in patients.

What it means for researchers

We do not know enough about the role of placebo and nocebo effects following the prescription of a non-drug intervention. Research should be conducted on the subject given the popularity of complementary and alternative medicine.

What it means for policymakers

The proliferation of information systems like the Internet for example, can parasitize a patient when making treatment. It may have more side effects than reason because of a nocebo effect. A doctor-patient relationship of trust, persuasive and optimistic is essential to prevent it.

Références

Benedetti F, Carlino E, Pollo A (2011). How placebos change the patient’s brain. Neuropsychopharmacology Reviews, 36, 339-354.

Benson H Dusek JA, Sherwood JB, Lam P, Bethea CF, Carpenter W, Levitsky S, Hill PC, Clem DW Jr, Jain MK, Drumel D, Kopecky SL, Mueller PS, Marek D, Rollins S, Hibberd PL (2006). Study of the Therapeutic Effects of Intercessory Prayer (STEP) in cardiac bypass patients: A multicenter randomized trial of uncertainty and certainty of receiving intercessory prayer. American Heart Journal, 151, 934-942.

Bingel U, Wanigasekera V, Wiech K, Ni Mhuircheartaigh R, Lee MC, Ploner M, Tracey I (2011). Drug efficacy – The effect of treatment expectation on drug efficacy: Imaging the analgesic benefit of the opioid remifentanil. Science Translational Medicine, 3, 70-14.

Colloca L, Miller FG (2011). The nocebo effect and its relevance for clinical practice. Psychosomatic Medicine, 73, 598-603.

Colloca L, Sigaudo M, Benedetti F (2008). The role of learning in nocebo and placebo effects. Pain, 136, 211-218.

Scott DJ, Stohler CS, Egnatuk CM, Wang H, Koeppe RA, Zubieta JK (2008). Placebo and nocebo effects are defined by opposite opioid and dopaminergic responses. Archives of General Psychiatry, 65, 220-231.

Hrobjartsson A, Gotzsche PC (2001). Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. Is placebo powerless? New England Journal of Medicine, 344, 1594-1602.

Hsieh JC, Stone-Elander S, Ingvar M (1999). Anticipatory coping of pain expressed in the human anterior cingulate cortex: a positron emission tomography study. Neuroscience Letter, 262, 61-64.

Koyama T, McHaffie JG, Laurienti PJ, Coghill RC (2005). The subjective experience of pain: where expectations became reality. Proceedings of the National Academy of Sciences of the United States of America, 102, 12950-12955.

Lorenz J, Hauck M, Paur RC, Nakamura Y, Zimmerman R, Bromm B, Engel AK (2005). Cortical correlates of false expectations during pain intensity judgments – a possible manifestation of placebo/nocebo cognitions. Brain Behavior Immunology, 19, 283-295.

Ploghaus A, Narain C, Beckmann CF, Clare S, Bantick S, Wise R, Matthews PM, Rawlins JN, Tracey I (2001). Exacerbation of pain by anxiety is associated with activity in a hippocampal network. Journal of Neuroscience, 21, 9896-9903.

Porro CA, Baraldi P, Pagnoni G, Serafini M, Facchin P, Maieron M, Nichelli P (2002). Does anticipation of pain affect cortical nociceptive systems? Journal of Neuroscience, 22, 3206-3214.

Rief W, Nestoriuc Y, Weiss S, Welzel E, Barsky AJ, Hofmann SG (2009). Meta-analysis of the placebo response in antidepressant trials. Journal of Affective Disorders, 118, 1-8.

Sawamoto N, Honda M, Okada T, Hanakawa T, Kanda M, Fukuyama H, Konishi J, Shibasaki H (2000). Expectation of pain enhances responses to non-painful somatosensory stimulation in the anterior cingulate cortex and parietal operculum/posterior insula: an event-related functional magnetic resonance imaging study. Journal of Neuroscience, 20, 7438-7445.

Varelmann D, Pancaro C, Cappiello EC, Camann WR (2010). Nocebo-induced hyperalgesia during local anesthetic injectionAnesthesia and Analgesia, 110, 868-870.


To reference this Blog en Sante © article. 

Ninot G (2014). Definition of nocebo. Blog en Sante, L30.

© Copyright 2014 Grégory Ninot. All rights reserved.