Am J Med. 2015 (Feb); 128 (2): 126–9
Maddy Greville-Harris, PhD, Paul Dieppe, MD
School of Psychology,
University of Southampton,
Although there has been a lot of research looking at the placebo response, nocebo responses in the healthcare setting have been largely overlooked. This article explores the potential role of negative patient-doctor communication in facilitating nocebo responses in the medical consultation. We suggest that invalidation, that is, communicating a lack of understanding and acceptance to the patient (albeit unintentionally), is a key factor in understanding the nocebo response. This article reviews evidence from the experimental and healthcare setting, which suggests that the negative effects of invalidation may be stronger than we think.
KEYWORDS: Communicating understanding; Doctor–patient interaction; Health communication; Invalidation; Nocebo response; Placebo response; Validation
Much attention has been given to the so-called placebo
response, that is, people getting better in response to sham
or dummy treatments that contain no active ingredient.  The
opposite nocebo response, that is, people getting worse in
response to sham interventions, has also been recognized for
a long time, but has resulted in less attention from health
researchers, [2, 3] who often focus on the ethical concerns
around knowingly inducing such responses. [4–6]
Sham or dummy interventions, by definition, contain no
active ingredients. Thus, the placebo/nocebo response must
result from some other component of these interventions,
such as the context in which they are administered or the
dialogue that takes place between patients and healthcare
professionals. Two psychological theories dominate our
thinking about the ways in which placebo/nocebo responses
are mediated: conditioning and expectation. For
example, if we always take a red painkilling pill to relieve
a headache, soon taking an inert red pill can relieve our
pain, because we have unconsciously learned to associate a
red pill with pain relief (conditioning), or we expect the
pill to work (expectation). There are plenty of data to
support the relevance of each of these factors in both the
placebo and nocebo responses, [6–10] yet the examination of
other mechanisms involved, particularly in nocebo
research, has largely been overlooked. Although a lot of
work focuses on the nocebo responses that result from
information provision about possible drug side effects, [11–15]
little research has focused on the role of negative
communication between doctor and patient (ie, human
interactions) more generally in facilitating nocebo responses
in the healthcare setting.
Häuser et al  suggest that “doctor-patient communication
and the patient’s treatment expectations can have
considerable consequences, both positive and negative, on
the outcome of a course of medical therapy,” and yet there
has been little consideration of the nocebo responses
brought about by doctor-patient interactions. We propose
that the nocebo response can be facilitated by the patient
responding negatively to the conversations they have with
healthcare providers, who are advising them about interventions
designed to improve their health. Specifically,
we believe that, as well as the mechanisms just described,
a key factor in understanding the nocebo response is the
concept of validation and invalidation.
Validation and invalidation are constructs developed
by Linehan  and others, [17–19] initially used as strategies in
therapy  and more recently as communication strategies
within the healthcare setting.  Although validation is the act of
communicating acceptance and understanding to another person,
invalidation is the opposite, communicating nonunderstanding
to another. These constructs differ
from empathy and compassion
in that they focus on communicating
understanding and acceptance
rather than merely understanding
another (“empathy” ) or creating
feelings of warmth, kindness, and
support (“compassion” ).
Although there has been some
recent interest in the validation/invalidation construct, [18–20] as with
placebo and nocebo research, most
research interest in validation has
concentrated on positive outcomes
(the value of validation) rather than
negative effects (the damaging effects
of invalidation). Yet, Baumeister
et al  propose that the
power of “bad” human interactions
is stronger than “good” human interactions.
We believe that the
concept of “bad is more powerful than good” needs to be
considered in the context of nocebo/placebo research and that
we need to concentrate our attention more on how not to
invalidate people, rather than empathy, compassion, and
Our experimental findings from work with Anke Karl,
Roelie Hempel, and Tom Lynch (unpublished material,
2013) support this idea; in a laboratory task, 90 participants
carried out a series of math tasks designed to be stressful,
while their physiologic responses were measured. Participants
also rated their mood using a validated self-rated
questionnaire (the Positive and Negative Affect
Schedule ) and subsequently recorded how safe they felt
during the experiment and whether they would be willing to
take part in the study again. During the tasks, participants
were assigned randomly to receive validating, invalidating,
or no feedback from the experimenter. The experimenter
was trained to give consistently validating or invalidating
feedback as rated on an established behavior coding scale
(the Validation and Invalidation Behavior Coding Scale
[Fruzzetti 2010; unpublished material]). For example, if the
participant said that he/she found the task stressful, the
experimenter might say “I don’t understand why you found
it stressful — it’s just adding and subtracting numbers.”
(invalidating response) or “that’s understandable — lots of
people have said they found this task stressful.” (validating
There were significant differences between the invalidated
participants and the other 2 groups on many of our
measures, indicating a detrimental effect of invalidation in
terms of psychological and psychological functioning.
Invalidated participants showed significantly higher psychological
arousal, significantly lower perceived safety ratings,
higher ratings of negative mood, and less willingness
to take part in the study again compared with the other 2
groups. Although we hypothesized
that the placebo response
might be due to validation, it was
not the positive effects of validation
but the negative effects of
invalidation that were significant
in this setting. 
Results in the clinical setting
also supported this idea; consultations
with patients at a pain
management clinic were observed
and recorded, and semistructured
interviews were carried out with
these patients (comprising 5
women with chronic widespread
pain) and 4 consultants at the
clinic. During the interviews, we
played back excerpts from the
patient’s consultation to discuss
in more detail. Interviews were
then analyzed using thematic
analysis,  whereby common themes were identified from
the interview transcripts.
The interviews suggested that the effects of invalidation
were very damaging. Both patients and consultants
described many instances of feeling invalidated during
chronic pain consultations. Patients reported feeling dismissed
and disbelieved by healthcare providers, encountering
providers who did not invest in them or show insight
into their condition. Consultants described receiving conflict
and criticism from patients, and encountering patients who
held entrenched views or would not believe their diagnosis.
Patients described feeling hopeless and angry after invalidating
consultations, feeling an increased need to justify their
condition or to avoid particular doctors or treatment altogether.
Although the sample was small, these findings are
in line with previous work. [26–33] Thus, invalidation during
consultations may elicit powerful nocebo responses in
patients that have so far not been adequately researched.
Although our research highlights the potential damage of
invalidating interactions, Linton et al  propose that invalidating
feedback can be delivered unintentionally. Literature
on communication in healthcare puts emphasis on the
need for professionals to be compassionate, to empathize
with patients, and to reassure them without necessarily
considering how they will respond to such actions. The
validation/invalidation research highlights that professionals
who believe that they are being compassionate and empathetic
with the patient may be invalidating them, because
the kindly, reassuring interaction may be interpreted as
patronizing or indicative of a lack of belief in the severity of
the condition by the patient.  For example, reassuring
patients that there is nothing physically wrong with them,
when they are in a great deal of pain, can leave them feeling
misunderstood and delegitimized.
We also carried out an online study that highlighted the
importance of how validating and invalidating feedback is
perceived as well as delivered. A total of 425 participants
took part in an online questionnaire about their emotions.
Participants were randomly assigned to receive validating or
invalidating feedback online about their skills in regulating
their emotions. We found that feedback that was not in line
with participants’ own views of themselves, regardless of
whether such feedback was validating or invalidating, was
less likely to be believed.  Moreover, validating feedback
that was not in line with participants’ self-views was rated
as less validating. Thus, it seems that we can easily invalidate,
or fail to validate, if the intention of our words is
misperceived by the receiver, particularly if we are communicating
that we oppose the participant’s view of himself
or herself in some way.
It is part of being human to want to feel understood by
others, and our general life experience tells us that harsh
words and criticism can hurt and have lasting negative effects.
We believe that in the context of disease and illness
where we need to be understood by health care professionals,
the negative effects of an unsatisfactory human
interaction can be particularly important. As Olshansky1
states, “a cold, uncaring, disinterested and emotionless
physician will encourage a nocebo response. In contrast, a
caring, empathetic, physician fosters trust, strengthens
beneficent patient expectations, and elicits a strong placebo
response.. The doctor, the nurse, the healthcare provider
are the most valuable resources for healing patients.”
Our work indicates that the effects of invalidation may be
stronger than we think, and the damaging effects extend to
psychological changes in the body, as well as changes in our
emotions and behaviors. This could lead to worsening of
illness, and thus the “nocebo response.” Patients bring certain
beliefs and expectations to their health care professional,
which are molded by the culture they live in and their previous
experiences. Their expectations will undoubtedly affect the
outcome. In addition, some people may have been conditioned
by previous negative experiences to respond negatively to a
certain type of human interaction (Figure 1).We fully endorse
the previous research and rhetoric that emphasize the
importance of expectations and conditioning on nocebo
responses. However, the negative power of an invalidating
human to human interaction is potentially more important.
The authors thank Dr Anke Karl, Dr Roelie Hempel, and
Prof. Thomas Lynch for their input, help, expertise, and
supervision of the PhD research described during this review;
Prof. Alan Fruzzetti and his team for sharing their
expertise on validation/invalidation techniques; Laura Scott
for assistance in the experimental work; and the participants,
patients, and clinicians who took part in these studies.
Placebo and nocebo in cardiovascular health implications for healthcare, research, and the doctor-patient relationship.
J Am Coll Cardiol. 2007;49:415-421.
Colloca L, Sigaudo M, Benedetti F.
The role of learning in nocebo and placebo effects.
Häuser W, Hansen E, Enck P.
Nocebo phenomena in medicine: their relevance in everyday clinical practice.
Dtsch Arztebl Int. 2012;109: 459-465.
Benedetti F, Lanotte M, Lopiano L, Colloca L.
When words are painful: unraveling the mechanisms of the nocebo effect.
Colloca L, Benedetti F.
Nocebo hyperalgesia: how anxiety is turned into pain.
Curr Opin Anaesthesiol. 2007;20:435-439.
Enck P, Benedetti F, Schedlowski M.
New insights into the placebo and nocebo responses.
Jensen KB, Kaptchuk TJ, Kirsch I, et al.
Nonconscious activation of placebo and nocebo pain responses.
Proc Natl Acad Sci U S A. 2012;109:15959-15964.
Pollo A, Carlino E, Vase L, Benedetti F.
Preventing motor training through nocebo suggestions.
Eur J Appl Physiol. 2012;112: 3893-3903.
van Laarhoven AI, Vogelaar ML, Wilder-Smith OH, et al.
Induction of nocebo and placebo effects on itch and pain by verbal suggestions.
Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I.
Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses.
J Neurosci. 2003;23: 4315-4323.
Colloca L, Finniss D.
Nocebo effects, patient-clinician communication, and therapeutic outcomes.
Colloca L, Miller FG.
The nocebo effect and its relevance for clinical practice.
Psychosom Med. 2011;73:598-603.
Grimes DA, Schulz KF.
Nonspecific side effects of oral contraceptives: nocebo or noise?
Wells RE, Kaptchuk TJ.
To tell the truth, the whole truth, may do patients harm: the problem of the nocebo effect for informed consent.
Am J Bioeth. 2012;12:22-29.
Barsky AJ, Saintfort R, Rogers MP, Borus JF.
Nonspecific medication side effects and the nocebo phenomenon.
JAMA. 2002;287: 622-627.
Validation and psychotherapy.
In: Bohart A, Greenberg L, eds. Empathy Reconsidered: New Directions in Psychotherapy.
Washington, DC: American Psychological Association; 1997:353-392.
Fruzzetti A, Worrall J.
Accurate expression and validating responses:
a transactional model for understanding individual and relationship distress.
In: Sullivan K, Davila J, eds.
Support Processes in Intimate Relationships.
New York: Oxford Press; 2010:121-152.
Shenk CE, Fruzzetti AE.
The impact of validating and invalidating responses on emotional reactivity.
J Soc Clin Psychol. 2011;30:163-183.
Linton SJ, Boersma K, Vangronsveld K, Fruzzetti A.
Painfully reassuring? The effects of validation on emotions and adherence in a pain test.
Eur J Pain. 2011;16:592-599.
Vangronsveld KL, Linton SJ.
The effect of validating and invalidating communication on satisfaction, pain and affect in nurses suffering fromlow back pain during a semi-structured interview.
Eur J Pain. 2012;16:239-246.
The necessary and sufficient conditions of therapeutic personality change.
J Consult Psychol. 1957;21:95-103.
Introducing compassion-focused therapy.
Adv Psychiatr Treat. 2009;15:199-208.
Baumeister RF, Bratslavsky E, Finkenauer C, Vohs KD.
Bad is stronger than good.
Rev Gen Psychol. 2001;5:323-370.
Tellegen A, Watson D, Clark LA.
Development and validation of brief measures of positive and negative affect: the PANAS scales.
J Pers Soc Psychol. 1988;54:1063-1070.
Does Feeling Understood Matter? The Effects of Validating and Invalidating Interactions [doctoral thesis].
Exeter, UK: University of Exeter Medical School; 2013.
Werner A, Malterud K.
It is hard work behaving as a credible patient: encounters between women with chronic pain and their doctors.
Soc Sci Med. 2003;57:1409-1419.
Corbett M, Foster NE, Ong BN.
Living with low back pain- stories of hope and despair.
Soc Sci Med. 2007;65:1584-1594.
Frantsve LM, Kerns RD.
Patienteprovider interactions in the management of chronic pain: current findings within the context of shared
medical decision making.
Pain Med. 2007;8:25-35.
Eccleston C, Williams DC, Amanda C, Rogers WS.
Patients’ and professionals’ understandings of the causes of chronic pain: blame, responsibility and identity protection.
Soc Sci Med. 1997;456: 699-709.
Reid S, Whooley D, Crayford T, Hotopf M.
Medically unexplained symptomseGPs’ attitudes towards their cause and management.
Fam Pract. 2001;18:519-523.
Telling patients there is nothing wrong.
Br Med J. 1996;313:311-312.
Wileman L, May C, Chew-Graham CA.
Medically unexplained symptoms and the problem of power in the primary care consultation: a qualitative study.
Fam Pract. 2002;19:178-182.
Chew-Graham CA, May CR, Roland MO.
The harmful consequences of elevating the doctor-patient relationship to be a primary goal of the general practice consultation.
Fam Pract. 2004;21: 229-231.
Linton SJ, McCracken LM, Vlaeyen JW.
Reassurance: help or hinder in the treatment of pain.
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