Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis

Helt ny studie som har gjennomgått placebokontrollerte studier av kirurgi og konkluderer med at placebokirurgi ikke er etisk utfordrende siden reell kirurgi uansett ikke har noen særlig bedre effekt. Og komplikasjonene er ikke større ved placebokirurgi heller.

http://bmjopen.bmj.com/content/5/1/e007331.full

Conclusions The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated.

 

The Enduring Impact of What Clinicians Say to People With Low Back Pain

Beskriver hvilken påvirkning ord har på pasienter. Spesielt når helsepersonell forteller at man på beskytte f.eks. ryggen ved ryggsmerter. Helsepersonells ideer om ryggsmerter smitter over på pasientene, derfor er det viktig at helsepersonell holder seg oppdatert på forskning, spesielt smerteforskning siden det er stort sett smerte folk kommer til behandling for.

http://www.annfammed.org/content/11/6/527.full

Many messages from clinicians were interpreted as meaning the back needed to be protected. These messages could result in increased vigilance, worry, guilt when adherence was inadequate, or frustration when protection strategies failed.

CONCLUSIONS Health care professionals have a considerable and enduring influence upon the attitudes and beliefs of people with low back pain. It is important that this opportunity is used to positively influence attitudes and beliefs.

The magnitude of nocebo effects in pain: A meta-analysis

Denne viser atnocebo effekten er like stor som placebo effekten.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213146

The overall magnitude of the nocebo effect was moderate to large (lowest g = 0.62 (0.24-1.01) and highest g = 1.03 (0.63-1.43)) and highly variable (range of g = −0.43-4.05). The magnitudes and range of effect sizes was similar to those of placebo effects (d = 0.81) in mechanistic studies. In studies where nocebo effects were induced by a combination of verbal suggestions and conditioning, the effect size was larger (lowest g = 0.76 (0.39-1.14) and highest g = 1.17 (0.52-1.81)) than in studies where nocebo effects were induced by verbal suggestions alone (lowest g = 0.64 (−0.25-1.53) and highest g = 0.87 (0.40-1.34)). These findings are similar to those in the placebo literature. Since the magnitude of the nocebo effect is variable and sometimes large, this meta-analysis demonstrates the importance of minimizing nocebo effects in clinical practice.

The influence of expectation on spinal manipulation induced hypoalgesia: An experimental study in normal subjects

Nevner at kontekst og pasientens forventning om behandling har alt så si for effekten av behandling. Denne studien gjelder manipulering av ryggraden, men kan forventes å gjelde absolutt all behandling som gjøre på menneskekroppen hvor man tar på huden.

http://www.biomedcentral.com/1471-2474/9/19

The current study replicates prior findings of c- fiber mediated hypoalgesia in the lower extremity following SMT and this occurred regardless of expectation. A significant increase in pain perception occurred following SMT in the low back of participants receiving negative expectation suggesting a potential influence of expectation on SMT induced hypoalgesia in the body area to which the expectation is directed.

A growing body of evidence supports spinal manipulative therapy (SMT) as an effective treatment for low back pain [16]. Furthermore, the evidence is particularly strong when patients are classified into subgroups by patterns suggesting the likelihood of a favorable response [2,3,6]. Despite the positive findings of clinical trials, the mechanisms through which SMT acts are not established.

Hypoalgesia has been associated with SMT and has a postulated involvement in the clinical effectiveness [716]. For example, Vicenzino et al [14] observed greater pain free grip and pain pressure threshold in the forearm following SMT to the cervical spine. A prior study by our group found hypoalgesia of c- fiber mediated pain as measured by lessening of temporal summation in the lower extremity following SMT to the lumbar spine [7]. Temporal summation results from multiple painful stimuli of the same intensity applied at a frequency of less than 3 seconds and has been observed in both healthy subjects [1719] and those experiencing chronic pain [20,21]. Activation of the dorsal horn of the spinal cord has been directly observed with temporal summation in animal studies [2225]. Subsequently, we interpreted our prior findings of hypoalgesia of temporal summation following SMT in healthy participants as indicative of a pain inhibiting effect occurring at the dorsal horn.

A criticism of prior studies of SMT is a lack of consideration for the influence of non- specific effects such as placebo and expectation [2628]. The failure to account for non- specific effects may be significant as expectation has demonstrated a robust influence in the general pain literature [2940]. Specific to manual therapy, Kalauokalani et al [39] report on a secondary analysis of subjects with low back pain who were randomly assigned to receive either acupuncture or massage treatments. Subjects with higher expectations for the effectiveness of their assigned treatments demonstrated greater improvement in function. In our prior study, we attributed hypoalgesia of c- fiber mediated pain in response to SMT to a local spinal cord effect. However, a limitation of our prior study was the failure to account for the potential influence of non- specific effects. Therefore, the purpose of this study was to determine how subjects’ expectation about the effect of SMT would influence hypoalgesia. Similar to prior studies [715], we expected a hypoalgesic effect in response to SMT, however we hypothesized this effect would be greater in subjects receiving positive expectation regarding the SMT procedure as compared to those receiving neutral or negative expectation.

Effect of Instructional Set on Expected Pain in the Low Back. Change in expected pain in the low back following instructional set. Positive values indicate expectation of less pain. A statistical interaction occurred with participants receiving a positive expectation instructional set reporting expectations for less pain with quantitative sensory testing (QST) following spinal manipulative therapy (SMT) and those receiving a negative expectation instructional set reporting expectations for greater pain. Error bars represent 1 standard error of the mean (SEM). * indicates significant change at p ≤ 0.05.

Change in Pain Perception in the Low Back and Lower Extremity by Expectation Instructional Set. Change in pain perception in the low back and lower extremity following spinal manipulative therapy (SMT). Positive numbers indicate hypoalgesia, while negative numbers indicate hyperalgesia. A significant interaction was present in the low back suggesting that post SMT pain perception was dependent upon the group to which the participant was randomly assigned. Follow up pairwise comparison indicated a significant increase in pain perception in subjects receiving a negative expectation instructional set. No interaction was observed in the lower extremity of participants; however, a significant main effect occurred suggesting hypoalgesia regardless of group assignment. Error bars represent 1 standard error of the mean (SEM). * indicates a statistically significant change in pain perception in the low back following SMT at p ≤ 0.05.

This study provides preliminary evidence for the influence of a non- specific effect (expectation) on the hypoalgesia associated with a single session of SMT in normal subjects. We replicated our previous findings of hypoalgesia in the lower extremity associated with SMT to the low back. Additionally, the resultant hypoalgesia in the lower extremity was independent of an expectation instructional set directed at the low back. Conversely, participants receiving a negative expectation instructional set demonstrated hyperalgesia in the low back following SMT which was not observed in those receiving a positive or neutral instructional set.

 

A meta-ethnography of patients’ experience of chronic non-malignant musculoskeletal pain

Omfattende studie om kronisk smerte som kommer med reelle tiltak for å bedre tilstanden hos pasientene. Nevner spesielt en at en holdningsendring må skje hos legene og sykepleierene hvor man inkluderer pasientes subjektive opplevelse. Nevner grunnlaget for dagens medisin og objektifisering av pasienten: «Foucault412 described the paradoxical position of the clinical encounter, in which the doctor aims to diagnose a disease rather than understand the person’s experience: ‘If one wishes to know the illness from which he is suffering, one must subtract the individual, with his [or her] particular qualities’  »

http://www.journalslibrary.nihr.ac.uk/__data/assets/pdf_file/0010/94285/FullReport-hsdr01120.pdf

Conclusion: Our model helps us to understand the experience of people with chronic MSK pain as a constant adversarial struggle. This may distinguish it from other types of pain. This study opens up possibilities for therapies that aim to help a person to move forward alongside pain. Our findings call on us to challenge some of the cultural notions about illness, in particular the expectation of achieving a diagnosis and cure. Cultural expectations are deep-rooted and can deeply affect the experience of pain. We therefore should incorporate cultural categories into our understanding of pain. Not feeling believed can have an impact on a person’s participation in everyday life. The qualitative studies in this meta-ethnography revealed that people with chronic MSK pain still do not feel believed. This has clear implications for clinical practice. Our model suggests that central to the relationship between patient and practitioner is the recognition of the patient as a person whose life has been deeply changed by pain. Listening to a person’s narratives can help us to understand the impact of pain. Our model suggests that feeling valued is not simply an adjunct to the therapy, but central to it. Further conceptual syntheses would help us make qualitative research accessible to a wider relevant audience. Further primary qualitative research focusing on reconciling acceptance with moving forward with pain might help us to further understand the experience of pain. Our study highlights the need for research to explore educational strategies aimed at improving patients’ and clinicians’ experience of care. 

As part of a person’s struggle we described the fragmentation of body and self, and suggested that moving forward with pain involves a process of reintegrating the painful body. 

Under conditions of health, we perform actions automatically and remain unaware of our body until something goes wrong with it. Health presupposes that we remain unaware of our bodies.396 When in pain, the body emerges as an ‘alien presence’;
it ‘dys-appears’. I no longer am a body but have a body,388 and my body becomes an ‘it’ as opposed to an

I’. Wall399 describes this dualism as epitomised by the expression ‘my foot hurts me’ as if in some way the foot is apart from myself (p. 23). It is because ‘the body seizes our awareness particularly at times of disturbance, [that] it can come to appear “other” and opposed to the self’ (p. 70).388 This fragmentation of ‘mind trapped inside an alien body’ means that our bodies become mistrusted and ‘forgotten as a ground of knowledge’ (p. 86).388 Our concept ‘integrating my painful body’ implies an altered therapeutic relationship with the body in which the dualism of mind and body are broken down.

We do not know why certain patients can accept and redefine their sense of self and others cannot.
It may be related to the degree of disruption to self that is caused by pain. The enmeshment model developed by Pincus and Morley406 proposes that, if a person regards their ideal self as unobtainable in the presence of pain, they are less likely to accept chronic pain. The enmeshment model incorporates self-discrepancy theory,407 which proposes that the extent to which pain disrupts our lives depends on the meaning that it holds for us. In self-discrepancy theory meaning incorporates three constructs: (1) actual self – ‘your representation of the attributes that someone (yourself or another) believes you actually possess’; (2) ideal self – ‘your representation of the attributes that someone (yourself or another) would like you, ideally, to possess’; and (3) ought self – ‘your representation of the attributes that someone (yourself or another) believes you should or ought to possess’ (p. 320–1).407

However, it is ‘pathos’, the feeling of suffering and powerlessness, of ‘life going wrong’, that precedes a person’s visit to the doctor (p. 137).396 Our model suggests that central to the therapeutic relationship is the recognition of ‘pathos’; the patient is a subject rather than an ‘object’ of investigation. This concept is central to models of patient-centred care.413

We described a need for a person in pain to feel that the health-care professional is alongside them with their pain. Affirming a person’s experience and allowing an empathetic interpretation of their story is not an adjunct, but integral to health care.395

Our model also suggests possibilities that might help patients to move forward alongside their pain:

  • an integrated relationship with the painful body
  • redefining a positive sense of self now and in the future
  • communicating to, rather than hiding from, others the experience of pain
  • knowing that I am not the only one with pain (but I am still valued)
  • regaining a sense of reciprocity and social participation
  • recognising the limitations of the medical model
  • being empowered to experiment and change the way that I do things without the sanction of the health-care professional.

Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal Tear

Mer om at operasjoner ikke er bedre enn placebo ved mediskproblemer.

http://www.nejm.org/doi/full/10.1056/NEJMoa1305189

In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure.

Deconstructing the Placebo Effect and Finding the Meaning Response

Om placeboeffekten og at «mening» er bedre å bruke enn en placeborespons når vi snakker om behandling. Placebo-sukkerpillen har ingen effekt i kroppen, men meningen vi legger i den har det. Vi får en «meningsrespons». Selv medisiner eller operasjoner får bedre effekt når det er en «mening» bak det.

http://annals.org/article.aspx?articleid=715182

http://www.homeopathy.org/wp-content/uploads/downloads/2012/05/Mossman.pdf

We provide a new perspective with which to understand what for a half century has been known as the “placebo effect.” We argue that, as currently used, the concept includes much that has noth- ing to do with placebos, confusing the most interesting and im- portant aspects of the phenomenon. We propose a new way to understand those aspects of medical care, plus a broad range of additional human experiences, by focusing on the idea of “mean- ing,” to which people, when they are sick, often respond.

We review several of the many areas in medicine in which meaning affects illness or healing and introduce the idea of the “meaning response.” We suggest that use of this formulation, rather than the fixation on inert placebos, will probably lead to far greater insight into how treatment works and perhaps to real improvements in human well-being.

If we replace the word “placebo” in the second sentence with its definition from the first, we get: “The placebo effect is the therapeutic effect produced by [things] objectively without specific activity for the condition being treated.” This makes no sense whatsoever. Indeed, it flies in the face of the obvious. The one thing of which we can be absolutely certain is that placebos do not cause placebo effects. Placebos are inert and don’t cause anything.

Moreover, people frequently expand the concept of the placebo effect very broadly to include just about every conceivable sort of beneficial biological, social, or human interaction that doesn’t involve some drug well- known to the pharmacopoeia.

The concept of the placebo effect has been expanded much more broadly than this. Some attribute the effects of various alternative medical systems, such as homeopathy (33) or chiropractic (34), to the placebo effect. Others have described studies that show the positive effects of enhanced communication, such as Egbert’s (35), as “the placebo re- sponse without the placebo” (7). No wonder things are confusing.

Instead, they can be ex- plained by the “meanings” in the experiment: 1) Red means “up,” “hot,” “danger,” while blue means “down,” “cool,” “quiet” and 2) two means more than one. These effects of color (37– 40) and number (41, 42) have been widely replicated.

In this study, branded aspirin worked better than unbranded aspirin, which worked better than branded placebo, which worked better than unbranded placebo.

Aspirin relieves headaches, but so does the knowledge that the pills you are taking are “good” ones.

n a study of the benefits of aerobic exercise, two groups participated in a 10-week exercise program. One group was told that the exercise would enhance their aerobic capacity, while the other group was told that the exercise would enhance aerobic capacity and psychological well-being. Both groups improved their aerobic capacity, but only the second group improved in psychological well-being (actually “self-esteem”). The re- searchers called this “strong evidence . . . that exercise may enhance psychological well-being via a strong placebo effect” (44).

It seems reasonable to label all these effects (except, of course, of the aspirin and the exercise) as “mean- ing responses,” a term that seeks, among other things, to recall Dr. Herbert Benson’s “relaxation response” (45). Ironically, although placebos clearly cannot do anything themselves, their meaning can.

We define the meaning response as the physiologic or psychological effects of meaning in the origins or treatment of illness; meaning responses elicited after the use of inert or sham treatment can be called the “placebo effect” when they are desirable and the “nocebo effect” (46) when they are undesirable.

Insofar as medicine is meaningful, it can affect pa- tients, and it can affect the outcome of treatment (47– 49). Most elements of medicine are meaningful, even if practitioners do not intend them to be so. The physi- cian’s costume (the white coat with stethoscope hanging out of the pocket) (50), manner (enthusiastic or not), style (therapeutic or experimental), and language (51) are all meaningful and can be shown to affect the out- come; indeed, we argue that both diagnosis (52) and prognosis (53) can be important forms of treatment.

Likewise, acupuncture analgesia can be reversed with naloxone in animals (61) and people (62). To say that a treatment such as acupuncture “isn’t better than placebo” does not mean that it does nothing.

Surgery is particularly meaningful: Surgeons are among the elite of medical practitioners; the shedding of blood is inevitably meaningful in and of itself.

The intensity of the effect was shown to be correlated with “the strength of commitment to traditional Chinese culture.” These differences in longevity (up to 6% or 7% difference in length of life!) are not due to having Chinese genes but to having Chinese ideas, to knowing the world in Chinese ways. The effects of meaning on health and disease are not restricted to placebos or brand names but permeate life.

Practitioners can benefit clinically by conceptualizing this issue in terms of the meaning response rather than the placebo effect. Placebos are inert. You can’t do anything about them. For human beings, meaning is everything that placebos are not, richly alive and powerful.

One reason we are so ignorant is that, by focusing on placebos, we constantly have to address the moral and ethical issues of prescribing inert treatments (73, 74), of lying (75), and the like. It seems possible to evade the entire issue by simply avoiding placebos. One cannot, however, avoid meaning while engaging human beings. Even the most distant objects—the planet Venus, the stars in the constellation Orion—are meaningful to us, as well as to others (76).