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European Neuropsychopharmacology : the... Nov 2012Much literature has been written in the field of child psychiatry regarding the placebo as a tool to test drug efficacy in clinical trials, but quite little regarding... (Review)
Review
Much literature has been written in the field of child psychiatry regarding the placebo as a tool to test drug efficacy in clinical trials, but quite little regarding the placebo effect itself or its clinical use in child psychiatry. In this article, we aim to critically review the literature regarding the placebo effect in children and adolescents with mental disorders, focusing especially on factors influencing the placebo effect and how they may influence the interpretation of clinical trials. The placebo effect seems to be more marked in children than adults, and particularly in children and adolescents with depression, although it is pervasive across ages and is present in non-psychiatric conditions as well. The use of a placebo in clinical trials as a comparator with drugs that have moderate efficacy at most makes it difficult to obtain positive results, and much effort is needed to design very high quality clinical trials that may overcome the limitations of using a placebo. In addition, the placebo effect across ages and clinical conditions must be tested directly (compared with no treatment whenever possible), in order to characterise which placebos work for what and to determine their use in clinical settings.
Topics: Adolescent; Adolescent Development; Child; Child Development; Controlled Clinical Trials as Topic; Humans; Mental Disorders; Neurogenesis; Placebo Effect; Placebos; Psychology, Adolescent; Psychology, Child; Psychopharmacology; Psychotropic Drugs
PubMed: 22030230
DOI: 10.1016/j.euroneuro.2011.09.007 -
Journal of Nutritional Science and... 2019Tryptophan (TRP), a precursor of serotonin is believed to have an antidepressant effect. The pathway for brain uptake of TRP is shared by other large neutral amino... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Tryptophan, Vitamin B, and Nicotinamide-Containing Supplement Loading between Meals on Mood and Autonomic Nervous System Activity in Young Adults with Subclinical Depression: A Randomized, Double-Blind, and Placebo-Controlled Study.
Tryptophan (TRP), a precursor of serotonin is believed to have an antidepressant effect. The pathway for brain uptake of TRP is shared by other large neutral amino acids; therefore, the best time to take TRP may be between meals. No previous study has, however, designated the time of TRP dosing to improve mood. Further, the effects of TRP on autonomic nervous system (ANS) activity are unclear. This study investigated the effects of TRP, vitamin B, and nicotinamide-containing supplements loading between meals on mood and ANS activity in depressive young adults. Thirty depressive young adults were randomly allocated to receive TRP, vitamin B, and nicotinamide-containing supplements or a placebo supplements twice daily between meals for 7 d. Mood was measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Profile of Mood States (POMS). ANS activities were analyzed by heart rate variability power spectral analysis. Blood samples were assayed for plasma total TRP concentration. For analysis, TRP and placebo groups were further classified into two subgroups according to CES-D score (mild to moderate vs. severe depressive symptoms). The CES-D score significantly improved following both treatments in the severe depression subgroups, while the POMS depression score was significantly improved only in the TRP severe depression subgroup. There was no significant change in ANS activity or plasma total TRP in any group. TRP, vitamin B, and nicotinamide-containing supplements loading between meals can quickly improve depressed mood in quite low dose in young adults with severe subclinical depression.
Topics: Adolescent; Adult; Affect; Depression; Dietary Supplements; Double-Blind Method; Female; Heart Rate; Humans; Male; Niacinamide; Placebos; Tryptophan; Vitamin B 6; Young Adult
PubMed: 31902864
DOI: 10.3177/jnsv.65.507 -
Lancet (London, England) Nov 1994
Review
Topics: Bias; Complementary Therapies; Effect Modifier, Epidemiologic; Humans; Patient Acceptance of Health Care; Placebos; Research Design; Terminology as Topic; Treatment Outcome
PubMed: 7967992
DOI: 10.1016/s0140-6736(94)90757-9 -
The Annals of Pharmacotherapy Sep 1996To review literature on placebo response in anxiety, to discuss sources and levels of placebo response in various anxiety disorders, and to suggest methods to prevent... (Review)
Review
OBJECTIVE
To review literature on placebo response in anxiety, to discuss sources and levels of placebo response in various anxiety disorders, and to suggest methods to prevent high placebo response rates in clinical research trials.
DATA SOURCE
Data from scientific literature were identified using a MEDLINE search, and were extracted and summarized for this review.
STUDY SELECTION
Representative findings were selected from clinical and epidemiologic studies, review articles, letters to the editor, book chapters, and proceedings.
DATA EXTRACTION
Data from English-language reports of studies on humans were included. Only the most representative conclusions drawn from review articles were used.
DATA SYNTHESIS
Anxiety disorders in general are thought to be extremely susceptible to a variety of influences, including patient characteristics and environmental variables. Reported placebo response levels in clinical studies of anxiolytics for generalized anxiety disorder and panic disorder vary widely, with a tendency to be rather high, although studies in social phobia and obsessive compulsive disorder appear to have consistently low placebo response rates. Comparisons of anxiety studies with studies of other indications, such as depression, show similar overall placebo response rates. To determine efficacy, drug response rates and placebo response rates must be clearly differentiated.
CONCLUSIONS
Examination of the literature suggests that placebo response rates in studies of anxiolytics are influences by a number of factors, including both endogenous and exogenous variables. High placebo response rates may mask true drug response rates and may result from poor study design or lack of procedural standardization. The use of certain design methods may help to prevent high placebo response rates in anxiolytic clinical trials.
Topics: Anxiety Disorders; Follow-Up Studies; Humans; Panic; Placebo Effect; Placebos
PubMed: 8876864
DOI: 10.1177/106002809603000917 -
Cephalalgia : An International Journal... Sep 2003Probably because of its relative rarity as primary headache, there are few well-controlled clinical trials on cluster headache (CH) patients. Due to the severity of the... (Review)
Review
Probably because of its relative rarity as primary headache, there are few well-controlled clinical trials on cluster headache (CH) patients. Due to the severity of the pain, the placebo response in CH has been considered to be small. During the eighties the first double-blind, placebo-controlled trials were reported, and placebo responses demonstrated. Here we review the placebo response in CH trials in order to assess its magnitude and consider how future studies can be optimized. Six trials were identified with a double-blind, placebo-controlled, cross-over design testing treatments of acute CH. For those with a primary endpoint set to no or mild headache the placebo responses varied from 7 to 42%. In five of seven prophylactic trials, using a double-blind, placebo-controlled, parallel-group design, the placebo was merely used to set a baseline for comparison. The placebo responses were reported in only two trials. Here the response varies from 14 to 43%, the lowest value was reported using the strict endpoint; cessation of headache attacks. We conclude that a placebo response exists in trials of drugs on CH patients. Furthermore, this placebo response is of the same magnitude as that seen in migraine studies. We recommend the use of IHS guidelines when designing new trials. The possibility of a genuine biological mechanism responsible for the placebo response is discussed.
Topics: Cluster Headache; Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic
PubMed: 12950375
DOI: 10.1046/j.1468-2982.2003.00531.x -
Rhode Island Medical Journal (2013) May 2015What we believe we will experience from a treatment--our expectation--has a substantial impact on what we actually experience. Expectation has been established as a key... (Review)
Review
What we believe we will experience from a treatment--our expectation--has a substantial impact on what we actually experience. Expectation has been established as a key process behind the placebo effect. Studies in both laboratory and clinical settings consistently show that when people ingest a pharmacologically inert substance (placebo) but believe that it is an active substance, they experience both the subjective sensations and physiologic effects expected from that active substance. Expectation has an important place in the response to "real" treatment as well. This paper provides an overview of the data which point to the role of expectation in both the placebo effect and the response to treatment. These data suggest that clinicians might enhance the benefit of all treatments by promoting patients' positive expectations.
Topics: Attitude; Humans; Personality Tests; Placebo Effect; Placebos; Surveys and Questionnaires
PubMed: 25938400
DOI: No ID Found -
Annals of Behavioral Medicine : a... Jun 2015Expectancy often predicts nausea, but the extent to which placebo interventions can alter nausea is less clear. (Review)
Review
BACKGROUND
Expectancy often predicts nausea, but the extent to which placebo interventions can alter nausea is less clear.
PURPOSE
We conducted a systematic review to determine 1) if placebo interventions can affect nausea and 2) which features of these interventions are effective.
METHODS
Articles were identified via PsychInfo, Medline, and PubMed databases. We targeted instructional and conditioning interventions aimed at altering nausea via the placebo effect.
RESULTS
Fourteen studies were identified, nine instructional and five conditioning. Many found evidence suggesting that placebo interventions could alter nausea, but a few found no evidence or 'reverse' effects. Effective interventions tended to be those that were aimed at participants with high initial expectancies, with evidence that combined or conditioning manipulations were more effective than instructions.
CONCLUSIONS
These findings suggest that placebo interventions can alter nausea and that these may serve as a useful way of reducing the burden of nausea in practice.
Topics: Conditioning, Psychological; Humans; Nausea; Placebo Effect; Placebos
PubMed: 25515086
DOI: 10.1007/s12160-014-9670-3 -
Current Topics in Medicinal Chemistry 2005In psychiatry, particularly in antidepressant clinical studies, placebo-controlled trials often yield results that are very difficult to interpret because of robust... (Review)
Review
In psychiatry, particularly in antidepressant clinical studies, placebo-controlled trials often yield results that are very difficult to interpret because of robust placebo responses. Meta-analyses of trials in major depressive disorder (MDD) suggest that drug-placebo differences in response rates range from 11% to 18%. However, in trials of marketed antidepressants present in the FDA databases, antidepressant drugs were superior to placebo in only 45 out of 93 RCTs (48%), and the placebo response overall appears to have increased over time. This gradual increase in placebo response rates may lead to delays in bringing new antidepressant treatments to the market, increased costs of antidepressant drug development and, in some cases, decisions to stop the development of certain compounds, or FDA decisions to not approve new treatments. A number of possible contributing factors to this significant placebo response in MDD have been identified, but further studies are needed. Many of the remedies used by researchers to minimize the placebo response, such as lead-in periods or shortening the duration of study visits, have failed to show consistent benefits. From our analysis of published studies, it appears that expectations about the speed of response may be shaped by the duration of the trial and that most of the placebo response occurs in the first half of the trial, regardless of its duration. These observations have led us to develop a novel approach to the placebo response problem called the Sequential Parallel Comparison Design.
Topics: Antidepressive Agents; Controlled Clinical Trials as Topic; Humans; Placebos; Time Factors
PubMed: 16181132
DOI: 10.2174/156802605774297092 -
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 Neuroscience : the... Nov 2011There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and... (Review)
Review
There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.
Topics: Autonomic Nervous System; Brain; Clinical Trials as Topic; Humans; Nervous System Diseases; Neuroimaging; Placebo Effect; Placebos; Psychophysiology
PubMed: 22072664
DOI: 10.1523/JNEUROSCI.4099-11.2011