"Kirsch says it’s not quite correct for reporters to interpret his work by saying that antidepressants don’t work. It’s that he’s concluded they don’t work by rebalancing serotonin. Instead, they appear to work primarily through the placebo effect."
See: http://www.forbes.com/sites/fayeflam/2015/03/18/a-psychologist-explains-how-not-to-be-fooled-by-the-placebo-effect/
Should doctors use more placebos?
ReplyDeletehttp://www.medscape.com/viewarticle/835197?src=wnl_edit_bom_weekly
Placebo works pretty well.
From: Migraine Therapeutics in Adolescents. A Systematic Analysis and Historic Perspectives of Triptan Trials in Adolescents
Haihao Sun, MD, PhD; Eric Bastings, MD; Jean Temeck, MD; P. Brian Smith, MD, MPH, MHS; Angela Men, MD; Veneeta Tandon, PhD; Dianne Murphy, MD; William Rodriguez, MD, PhD
JAMA Pediatr. 2013;167(3):243-249.
Conclusions High placebo response rates are consistent across all trials and may represent the principal challenge in pediatric trials of drugs for abortive treatment of migraine. Enrichment with selection of subjects with long-lasting migraine attacks is not sufficient to overcome high placebo response rates. Another enrichment strategy, the nonrandomization of patients with an early placebo response, successfully reduces the high placebo response rate for rizatriptan and is a trial design that should be considered for future pediatric trials of abortive migraine therapeutics.
Pharmacologic Treatment of Pediatric Headaches. A Meta-analysis
Khalil El-Chammas, MD; Jill Keyes, MD; Nathan Thompson, MD; Jayanthi Vijayakumar, MBBS; Dorothy Becher, MPH; Jeffrey L. Jackson, MD, MPH
JAMA Pediatr. 2013;167(3):250-258.
Conclusions Topiramate and trazodone have limited evidence supporting efficacy for episodic migraines. Placebo was effective in reducing headaches. Other commonly used drugs have no evidence supporting their use in children and adolescents. More research is needed.
Placebo works pretty well.
Two phase 2 studies[1,2] presented at the 66th annual meeting of the American Academy of Neurology have tested the ability of monoclonal antibodies to prevent migraine headaches. In both studies, antibodies directed against the calcitonin gene-related peptide (CGRP) were employed. In the first study, 163 people with migraines from 5 to 14 days per month were given either a single intravenous dose of a drug called ALD403, or placebo, and followed for 24 weeks. Those who received the antibody had 66% fewer migraine days per month compared with a 52% reduction in those receiving placebo. Of those receiving the antibody, 16% had no migraine days at 12 weeks, whereas none in the placebo group were migraine-free at that point. There were no differences in side effects between the groups. In the second study, 217 people with an average of 4 to 14 migraine days per month received biweekly subcutaneous injections of placebo or a drug called LY2951742. Those who received this antibody had 63% fewer migraine days per month, compared with a 42% reduction in those receiving the placebo. Those receiving this antibody were more likely to have side effects, including pain at the injection site, upper respiratory infections, and abdominal pain, but overall the antibody was considered safe and well tolerated. The investigators concluded that these results potentially represent a new mechanism-based era in prevention and therapy for migraine.
From the Medscape Neurology Minute. Dr Alan Jacobs.
http://www.medscape.com/viewarticle/835033?nlid=71404_3001&src=wnl_edit_medp_neur&spon=26
1. Dodick DW, Goadsby PJ, Silberstein SD, et al; ALD403 study investigators. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014;13:1100-1107.
2. Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, Grayzel DS. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo controlled study. Lancet Neurol. 2014;13:885-892.
Placebo works better when it is expensive
ReplyDeleteEspay AJ, Norris MM, Eliassen JC, Dwivedi A, Smith MS, Banks C, Allendorfer JB, Lang AE, Fleck DE, Linke MJ, Szaflarski JP. Placebo effect of medication cost in Parkinson disease: A randomized double-blind study. Neurology. 2015 Jan 28.
Abstract
OBJECTIVE:
To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions.
METHODS:
We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis.
RESULTS:
Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions.
CONCLUSION:
Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies.
CLASSIFICATION OF EVIDENCE:
This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.
From a colleague regarding the Forbes article: Interesting article. Certainly, many of our developmentally challenged patients who seem unable to perceive the idea of placebo would argue for benefit of the actual med when they are “better”. Of course, placebo by proxy reporter may also occur.
ReplyDeleteIs the placebo effect in some people’s genes?
ReplyDeletehttp://www.reuters.com/article/2015/04/16/us-placebo-effect-genes-idUSKBN0N62L220150416?feedType=RSS&feedName=healthNews
See: Kathryn T. Hall, Joseph Loscalzo, Ted J. Kaptchuk. Genetics and the placebo effect: the placebome. Trends in Molecular Medicine. In Press, Corrected Proof, Available online 14 April 2015
Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.
ReplyDeleteSee: Shang A, Huwiler-Müntener K, Nartey L, Jüni P, Dörig S, Sterne JA, Pewsner D, Egger M. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet. 2005 Aug 27-Sep 2;366(9487):726-32.
"The story is told of a 5-year-old who witnessed a horrific accident and suffered from the trauma, which severely affected his studies.
ReplyDeleteThe parents took the boy to doctors and psychologists, to no avail.
When they took him to Rav Chaim, he told the boy that he had a special medicine that would certainly work.
He left the room and returned with a small bottle, telling the boy to take a spoonful every day.
A week later, the child returned and declared that he felt better and that all of his symptoms had disappeared. Rav Chaim turned to the father and said, 'Do you know what was in the bottle? Water.'"
“The only previous placebo-controlled study in patients with advanced knee osteoarthritis found that actual surgery was no better than sham surgery (skin incisions only). Published 10 years ago, this report marked an important turning point for the orthopedic community, provoking unprecedented criticism and even hostility. Not surprising since it was such a blow to professional pride and a potential threat to a very common and lucrative orthopedic procedure.
ReplyDelete“My team decided to repeat the study, but with patients who had only a torn meniscus. Patients with a torn meniscus seemed more likely to respond to surgery because they didn’t have all the nonspecific damage associated with advanced osteoarthritis.
“We inserted an arthroscope through small ‘keyholes’ in the skin, which allowed us to see inside the knee. Through this hole we inserted tools that could trim the torn meniscus and smooth ragged edges of what remained.
“The 146 volunteer patients all received anesthesia and incisions. Half received actual surgery; the other half got the sham procedure, which was just taking a peek inside the knee, but no trimming. The patients didn’t know which procedure they got—real surgery or sham surgery.
“Both groups had equivalent results. A year later, approximately 80% of patients in both groups said their knees felt better, and over 90% said they would choose the same method again, even the patients who had fake surgery.
See more at: http://www.psychiatrictimes.com/blogs/knee-surgery-think-twice#sthash.o5NHtdDJ.dpuf
From the Ig Nobel Prizes 2008:
ReplyDeleteMEDICINE PRIZE. Dan Ariely of Duke University (USA), Rebecca L. Waber of MIT (USA), Baba Shiv of Stanford University (USA), and Ziv Carmon of INSEAD (Singapore) for demonstrating that high-priced fake medicine is more effective than low-priced fake medicine..
REFERENCE: "Commercial Features of Placebo and Therapeutic Efficacy," Rebecca L. Waber; Baba Shiv; Ziv Carmon; Dan Ariely, Journal of the American Medical Association, March 5, 2008; 299: 1016-1017.
WHO ATTENDED THE CEREMONY: Dan Ariely
See: http://www.improbable.com/ig/winners/
See March 20, 2015 3:08 am above.
Some placebos are more effective than others, and these differences can influence the apparent outcomes of clinical trials, according to a systematic review and meta-analysis of osteoarthritis trials.
ReplyDelete"More surprising than the fact that all placebos are not equal is the magnitude of that difference," Dr. Raveendhara R. Bannuru, from Tufts Medical Center, Boston, told Reuters Health by email. "In particular, we found that intra-articular placebo was more effective than the active drug Tylenol."
In a recent study, Dr. Bannuru's team found that conclusions regarding the effectiveness of various pharmacological treatments for knee osteoarthritis could differ based on how alternative placebos were treated within a network analysis model.
Their current investigation used a network meta-analysis to determine whether the different placebo interventions used in knee osteoarthritis trials differ in efficacy and to quantify the effect of differential placebo effects on active-treatment effect estimates...
Intra-articular placebo and topical placebo had significantly greater effects than oral placebo, with the effect size of oral placebo being comparable to that of acetaminophen...
The choice of placebo significantly influenced the apparent relative effect sizes of active treatments. Depending on the placebo model used, for example, the ranking of oral nonselective nonsteroidal anti-inflammatory drugs could range from third to most effective.
"Our results should be interpreted with care," the researchers noted. "The purpose of this study was not to determine the presence versus absence of an absolute placebo effect but rather to determine the relative effects of different placebo interventions. This analysis enabled us to consider how these differences affect estimates of active treatment effects, as well as to better understand the embedded therapeutic benefit that placebo interventions may confer."
"The take-home message for physicians and researchers is that placebos are not null in efficacy, nor are they equivalent to one another," Dr. Bannuru said. "Physicians should consider the method of administration when choosing knee osteoarthritis treatments. For researchers, selection of appropriate placebo controls is an important consideration in the design of future clinical trials. Also, the comparative effectiveness of active treatments depends on the type of placebo it is being compared to."
http://www.medscape.com/viewarticle/848718?src=wnl_edit_medn_wir&uac=60196BR&spon=34&impID=779223&faf=1