-
Journal of the Royal Society of Medicine Jun 2013
Topics: Deception; Humans; Informed Consent; Placebo Effect; Placebos; Practice Patterns, Physicians'; Prescriptions
PubMed: 23761577
DOI: 10.1177/0141076813489969 -
PloS One 2014Surveys of doctors suggest that they use placebos and placebo effects clinically to help patients. However, patients' views are not well-understood. We aimed to identify...
BACKGROUND
Surveys of doctors suggest that they use placebos and placebo effects clinically to help patients. However, patients' views are not well-understood. We aimed to identify when and why placebo-prescribing in primary care might be acceptable and unacceptable to patients.
METHODS
A purposive diverse sample of 58 English-speaking adults (18 men; aged 19-80 years) participated in 11 focus groups. Vignettes describing doctors prescribing placebos in primary care were used to initiate discussions. Data were analyzed inductively.
RESULTS
Participants discussed diverse harms and benefits of placebo-prescribing for individual patients, carers, healthcare providers, and society. Two perspectives on placebo-prescribing were identified. First, the "consequentialist" perspective focused on the potential for beneficial outcomes of placebo-prescribing. Here, some participants thought placebos are beneficial and should be used clinically; they often invoked the power of the mind or mind-body interactions. Others saw placebos as ineffective and therefore a waste of time and money. Second, the "respecting autonomy" perspective emphasized the harms caused by the deceptive processes thought necessary for placebo-prescribing. Here, participants judged placebo-prescribing unacceptable because placebo-prescribers deceive patients, thus a doctor who prescribes placebos cannot be trusted and patients' autonomy is compromised. They also saw placebo-responders as gullible, which deterred them from trying placebos themselves. Overall, the word "placebo" was often thought to imply "ineffective"; some participants suggested alternative carefully chosen language that could enable doctors to prescribe placebos without directly lying to patients.
CONCLUSIONS
Negative views of placebos derive from beliefs that placebos do not work and/or that they require deception by the doctor. Positive views are pragmatic in that if placebos work then any associated processes (e.g. mechanisms, deception) are deemed unimportant. Public education about placebos and their effects is warranted and research to identify optimal ways of harnessing placebo effects in clinical practice is needed.
Topics: Adult; Aged; Aged, 80 and over; Female; Focus Groups; Humans; Male; Middle Aged; Patients; Placebo Effect; Placebos; Treatment Outcome; Young Adult
PubMed: 25006673
DOI: 10.1371/journal.pone.0101822 -
Clinical Gastroenterology and... Dec 2014It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn's disease (CD), to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn's disease (CD), to understand disease progression, and to calculate sample size. We conducted a systematic review and meta-analysis of rates of response to placebo in trials of patients with fistulizing CD.
METHODS
We searched MEDLINE, EMBASE, EMBASE CLASSIC, and the Cochrane central register of controlled trials for randomized controlled trials (RCTs) comparing pharmacologic agents with placebo in adults with fistulizing CD. We identified studies that reported complete fistula closure, partial closure, or response. Data were extracted as intention-to-treat analyses and pooled by using a random-effects model. Proportions of patients who received placebo and had complete or partial fistula(e) closure were calculated, with 95% confidence intervals (CIs). The effects of trial characteristics on the magnitude of response to placebo were examined.
RESULTS
Thirteen RCTs were eligible for our analysis; these included 579 patients assigned to placebo groups. The pooled rate of response to placebo, among all RCTs, for complete fistula closure was 15.6% (95% CI, 10.9%-20.9%), with significant heterogeneity (I(2) = 62.5%, P = .001). The pooled rate of response to placebo for partial fistula closure or response in 9 trials, comprising 423 patients, was 18.3% (95% CI, 14.8%-22.1%). Rates of response to placebo were significantly lower in trials with shorter durations of therapy and shorter intervals to assessment of fistula closure. Neither exposure to the pharmacologic agent during the induction phase of the same (or related) RCT nor concomitant medications had any effect.
CONCLUSIONS
In a meta-analysis of rate of response to placebo in patients with fistulizing CD, we found that fistulae closed in almost 1/6 patients given placebo in RCTs of pharmacologic agents. Future research should identify characteristics of patients that predict response to placebo.
Topics: Crohn Disease; Fistula; Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic
PubMed: 25218669
DOI: 10.1016/j.cgh.2014.08.038 -
Revista Brasileira de Psiquiatria (Sao... Mar 2009To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate... (Review)
Review
OBJECTIVE
To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics.
METHOD
Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms 'amisulpride', 'aripiprazole', 'clozapine', 'olanzapine', 'quetiapine', 'risperidone', 'sertindole', 'ziprasidone' and 'zotepine'. Main efficacy parameters were calculated using the proportion of 'events' (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale) and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo.
RESULTS
The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic.
CONCLUSIONS
Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.
Topics: Antipsychotic Agents; Humans; Meta-Analysis as Topic; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 19506777
DOI: 10.1590/s1516-44462009000100013 -
BMJ (Clinical Research Ed.) May 2014To investigate whether placebo controls should be used in the evaluation of surgical interventions. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate whether placebo controls should be used in the evaluation of surgical interventions.
DESIGN
Systematic review.
DATA SOURCES
We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013.
STUDY SELECTION
Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques.
DATA EXTRACTION
Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies.
RESULTS
In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection.
CONCLUSIONS
Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged.
Topics: Humans; Placebos; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 24850821
DOI: 10.1136/bmj.g3253 -
The Journal of Physiology Oct 2016We analysed the placebo response at the single-neuron level in the thalamus of Parkinson patients to see the differences between first-time administration of placebo and...
KEY POINTS
We analysed the placebo response at the single-neuron level in the thalamus of Parkinson patients to see the differences between first-time administration of placebo and administration after pharmacological pre-conditioning. When the placebo was given for the first time, it induced neither clinical improvement, as assessed through muscle rigidity reduction at the wrist, nor neuronal changes in thalamic neurons. However, if placebo was given after two, three or four prior administrations of an anti-Parkinson drug, apomorphine, it produced both clinical and neuronal responses. Both the magnitude and the duration of these placebo responses depended on the number of prior exposures to apomorphine, according to the rule: the greater the number of previous apomorphine administrations, the larger the magnitude and the longer the duration of the clinical and neuronal placebo responses. These findings show that learning plays a crucial role in the placebo response and suggest that placebo non-responders can be turned into placebo responders, with important clinical implications.
ABSTRACT
Placebos have been found to affect the patient's brain in several conditions, such as pain and motor disorders. For example, in Parkinson's disease, a placebo treatment induces a release of dopamine in the striatum and changes the activity of neurons in both thalamic and subthalamic nuclei. The present study shows that placebo administration for the first time induces neither clinical nor neuronal improvement in Parkinson patients who undergo implantation of electrodes for deep brain stimulation. However, this lack of placebo responsiveness can be turned into substantial placebo responses following previous exposure to repeated administrations of the anti-Parkinson agent apomorphine. As the number of apomorphine administrations increased from one to four, both the clinical response and the neuronal activity in the ventral anterior and anterior ventrolateral thalamus increased. In fact, after four apomorphine exposures, placebo administration induced clinical responses that were as large as those to apomorphine, along with long-lasting neuronal changes. These clinical placebo responses following four apomorphine administrations were again elicited after a re-exposure to a placebo 24 h after surgery, but not after 48 h. These data indicate that learning plays a crucial role in placebo responsiveness and suggest that placebo non-responders can be turned into responders, with important implications in the clinical setting.
Topics: Aged; Apomorphine; Deep Brain Stimulation; Dopamine Agonists; Female; Humans; Male; Middle Aged; Neurons; Parkinson Disease; Placebo Effect; Placebos
PubMed: 26861164
DOI: 10.1113/JP271322 -
Annals of African Medicine 2017The use of control group in clinical trials has been universally acclaimed by researchers to effectively help discriminate between the actual effects of an intervention... (Review)
Review
The use of control group in clinical trials has been universally acclaimed by researchers to effectively help discriminate between the actual effects of an intervention and those arising from other factors. However, the choice of the control that provided both scientific and ethical acceptability among researchers has been a source of intense debate. We conducted a literature search on the use of placebo and active controls in clinical trials and X-ray the arguments for and against both choices in randomized control trials and concluded by highlighting the scenarios where the use of placebo is justified.
Topics: Antipsychotic Agents; Biomedical Research; Ethics, Medical; Humans; Mental Disorders; Placebos; Randomized Controlled Trials as Topic
PubMed: 28671148
DOI: 10.4103/aam.aam_211_16 -
The Cochrane Database of Systematic... Jun 2014Elevation of pulmonary pressure is no longer a rare disease, given its multifactorial etiology. However data on the actual incidence of this condition are still limited,... (Review)
Review
BACKGROUND
Elevation of pulmonary pressure is no longer a rare disease, given its multifactorial etiology. However data on the actual incidence of this condition are still limited, and controversies regarding its management are ongoing. Use of anticoagulation in the management of pulmonary hypertension is based on the presence of in situ thrombosis in the patient with pulmonary arterial hypertension (PAH) and on retrospective evidence of clinical benefit. Current practice is dependent mostly on expert opinion and individualised experience. The real benefit of its use in different types of pulmonary hypertension is still debatable, and the therapeutic target of the international normalised ratio (INR) among treated patients remains inconclusive. Adverse outcomes associated with anticoagulants are significant and can include fatal haemorrhage. Justification for the use of this intervention requires critical evaluation of randomised controlled trials.
OBJECTIVES
1. To evaluate the effectiveness of, and potential adverse events associated with, anticoagulation in the management of pulmonary hypertension (PH).2. To evaluate the effective therapeutic INR in pulmonary hypertensive patients receiving anticoagulants (North American centres 1.5 to 2.5, European centres 2.0 to 3.0).
SEARCH METHODS
We identified trials through searches of the following databases.Cochrane Airways Group Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library; MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCOhost); Clinical trials.gov and the World Health Organization (WHO) trials portal. The trial search date was 28 March 2014.
SELECTION CRITERIA
We planned to include only randomised controlled trials. Participants with PH with co-morbidities including medical conditions requiring long-term anticoagulation were to be included. We also planned to include trials comparing any anticoagulant with placebo.
DATA COLLECTION AND ANALYSIS
Review authors (IE and HE) independently appraised all identified citations to establish their relevance for inclusion in the review. IE and HE independently screened the titles and abstracts of all identified potential studies for inclusion.
MAIN RESULTS
No eligible trials were identified for inclusion in this review.
AUTHORS' CONCLUSIONS
No eligible studies were identified for inclusion in this review. Although our review of available non-randomised studies shows beneficial effect, this finding should be interpreted with caution since there are likely to be biases associated with their design and our methods were not designed to identify, appraise and summarise evidence from them. So that better decisions can be made regarding the effectiveness of this intervention, well-designed randomised controlled trials are needed.
Topics: Anticoagulants; Humans; Hypertension, Pulmonary; International Normalized Ratio; Placebos
PubMed: 24887213
DOI: 10.1002/14651858.CD010695.pub2 -
Tidsskrift For Den Norske Laegeforening... Nov 2017
Topics: Acupuncture Therapy; Humans; Placebos
PubMed: 29181912
DOI: 10.4045/tidsskr.17.0478 -
Pain Sep 2009The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during...
The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p=0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.
Topics: Adult; Analgesia; Analgesics; Analysis of Variance; Brain; Brain Mapping; Female; Humans; Image Processing, Computer-Assisted; Lasers; Magnetic Resonance Imaging; Male; Nerve Net; Oxygen; Pain; Pain Measurement; Pain Threshold; Placebos; Young Adult
PubMed: 19523766
DOI: 10.1016/j.pain.2009.04.003