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The Cochrane Database of Systematic... Nov 2020This is an update of a Cochrane Review, first published in 2005. Hemifacial spasm (HFS) is characterised by unilateral, involuntary contractions of the muscles...
BACKGROUND
This is an update of a Cochrane Review, first published in 2005. Hemifacial spasm (HFS) is characterised by unilateral, involuntary contractions of the muscles innervated by the facial nerve. It is a chronic disorder, and spontaneous recovery is very rare. The two treatments routinely available are microvascular decompression and intramuscular injections with botulinum toxin type A (BtA).
OBJECTIVES
To compare the efficacy, safety, and tolerability of BtA versus placebo in people with HFS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. We ran the electronic database search, with no language restrictions, in July 2020.
SELECTION CRITERIA
Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with HFS.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed records. We planned to select included studies, extract data using a paper pro forma, and evaluate the risk of bias. We resolved disagreements by consensus, or by consulting a third review author. We planned to perform meta-analyses. The primary efficacy outcome was HFS-specific improvement. The primary safety outcome was the proportion of participants with any adverse event.
MAIN RESULTS
We found no parallel-group randomised controlled trials comparing BtA and placebo in HFS.
AUTHORS' CONCLUSIONS
We did not find any randomised trials that evaluated the efficacy and safety of botulinum toxin type A in people with hemifacial spasm, so we are unable to draw any conclusions. Observational data show a strong association between BtA treatment and symptom improvement, and a favourable safety profile. While it is unlikely that future placebo-controlled RCTs will evaluate absolute efficacy and safety, they should address relevant questions for both people with HFS (such as long-term effects, quality of life, and other patient-reported outcomes), and clinicians (such as relative effectiveness of different BtA formulations and schemes of treatment) to better guide clinical practice.).
Topics: Botulinum Toxins, Type A; Hemifacial Spasm; Humans; Neuromuscular Agents; Placebos
PubMed: 33211908
DOI: 10.1002/14651858.CD004899.pub3 -
The Cochrane Database of Systematic... Jul 2021Dentinal hypersensitivity is characterized by short, sharp pain from exposed dentine that occurs in response to external stimuli such as cold, heat, osmotic, tactile or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dentinal hypersensitivity is characterized by short, sharp pain from exposed dentine that occurs in response to external stimuli such as cold, heat, osmotic, tactile or chemicals, and cannot be explained by any other form of dental defect or pathology. Laser therapy has become a commonly used intervention and might be effective for dentinal hypersensitivity.
OBJECTIVES
To assess the effects of in-office employed lasers versus placebo laser, placebo agents or no treatment for relieving pain of dentinal hypersensitivity.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2020, Issue 9), MEDLINE Ovid (1946 to 20 October 2020), Embase Ovid (1980 to 20 October 2020), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 20 October 2020), and LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; from 1982 to 20 October 2020). Conference proceedings were searched via the ISI Web of Science and ZETOC, and OpenGrey was searched for grey literature. The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in which in-office lasers were compared to placebo or no treatment on patients aged above 12 years with tooth hypersensitivity.
DATA COLLECTION AND ANALYSIS
Two review authors independently and in duplicate screened the search results, extracted data, and assessed the risk of bias of the included studies. Disagreement was resolved by discussion. For continuous outcomes, we used mean differences (MD) and 95% confidence intervals (CI). We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE.
MAIN RESULTS
We included a total of 23 studies with 936 participants and 2296 teeth. We assessed five studies at overall low risk of bias, 13 at unclear, and five at high risk of bias. 17 studies contributed data to the meta-analyses. We divided the studies into six subgroups based on the type of laser and the primary outcome measure. We assessed the change in intensity of pain using quantitative pain scale (visual analogue scale (VAS) of 0 to 10 (no pain to worst possible pain)) when tested through air blast and tactile stimuli in three categories of short (0 to 24 hours), medium (more than 24 hours to 2 months), and long term (more than 2 months). Results demonstrated that compared to placebo or no treatment the application of all types of lasers combined may reduce pain intensity when tested through air blast stimuli at short term (MD -2.24, 95% CI -3.55 to -0.93; P = 0.0008; 13 studies, 978 teeth; low-certainty evidence), medium term (MD -2.46, 95% CI -3.57 to -1.35; P < 0.0001; 11 studies, 1007 teeth; very low-certainty evidence), and long term (MD -2.60, 95% CI -4.47 to -0.73; P = 0.006; 5 studies, 564 teeth; very low-certainty evidence). Similarly, compared to placebo or no treatment the application of all types of lasers combined may reduce pain intensity when tested through tactile stimuli at short term (MD -0.67, 95% CI -1.31 to -0.03; P = 0.04; 8 studies, 506 teeth; low-certainty evidence) and medium term (MD -1.73, 95% CI -3.17 to -0.30; P = 0.02; 9 studies, 591 teeth; very low-certainty evidence). However, there was insufficient evidence of a difference in pain intensity for all types of lasers when tested through tactile stimuli in the long term (MD -3.52, 95% CI -10.37 to 3.33; P = 0.31; 2 studies, 184 teeth; very low-certainty evidence). Most included studies assessed adverse events and reported that no obvious adverse events were observed during the trials. No studies investigated the impact of laser treatment on participants' quality of life.
AUTHORS' CONCLUSIONS
Limited and uncertain evidence from meta-analyses suggests that the application of laser overall may improve pain intensity when tested through air blast or tactile stimuli at short, medium, or long term when compared to placebo/no treatment. Overall, laser therapy appears to be safe. Future studies including well-designed double-blinded RCTs are necessary to further investigate the clinical efficacy of lasers as well as their cost-effectiveness.
Topics: Bias; Dentin Sensitivity; Humans; Laser Therapy; Pain Measurement; Placebos; Randomized Controlled Trials as Topic
PubMed: 34255856
DOI: 10.1002/14651858.CD009434.pub2 -
Pain Aug 2016Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with... (Review)
Review
Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22 studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Provided that nondisclosure is preauthorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated.
Topics: Analgesics; Animals; Humans; Pain; Pain Management; Placebos; Treatment Outcome
PubMed: 27023425
DOI: 10.1097/j.pain.0000000000000566 -
JAMA Psychiatry Nov 2015High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
High placebo responses have been observed across a wide range of pathologies, severely impacting drug development.
OBJECTIVE
To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD).
DESIGN, SETTING, AND PARTICIPANTS
In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) were studied with positron emission tomography and the µ-opioid receptor-selective radiotracer [11C]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect.
MAIN OUTCOMES AND MEASURES
Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of µ-opioid receptor binding.
RESULTS
Higher baseline µ-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r = 0.48; P = .02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, were associated with increased placebo-induced µ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala (nucleus accumbens: r = 0.6; P < .001). Placebo-induced endogenous opioid release in these regions was associated with better antidepressant treatment response, predicting 43% of the variance in symptom improvement at the end of the antidepressant trial.
CONCLUSIONS AND RELEVANCE
These data demonstrate that placebo-induced activation of the µ-opioid system is implicated in the formation of placebo antidepressant effects in patients with MDD and also participate in antidepressant responses, conferring illness resiliency, during open administration.
TRIAL REGISTRATION
clinicaltrials.gov Identifier:NCT02178696.
Topics: Adult; Analgesics, Opioid; Depressive Disorder, Major; Female; Fentanyl; Humans; Male; Middle Aged; Nucleus Accumbens; Placebo Effect; Placebos; Positron-Emission Tomography; Receptors, Opioid, mu; Selective Serotonin Reuptake Inhibitors; Single-Blind Method; Treatment Outcome; Young Adult
PubMed: 26421634
DOI: 10.1001/jamapsychiatry.2015.1335 -
The Cochrane Database of Systematic... Jan 2008Obsessive compulsive disorder is a common and disabling disorder. A significant proportion of patients manifest a chronic course. Individual randomised controlled trials... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obsessive compulsive disorder is a common and disabling disorder. A significant proportion of patients manifest a chronic course. Individual randomised controlled trials (RCTs) have shown that selective serotonin re-uptake inhibitors (SSRIs) are effective in this condition. Previous systematic reviews or meta-analyses summarising the evidence are methodologically problematic or limited in the scope of their analysis.
OBJECTIVES
To examine the efficacy and adverse effects of serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD) in adults.
SEARCH STRATEGY
CCDANCTR-Studies and CCDANCTR-References were searched on 12/11/2007. Reference lists were checked. Experts in the field were contacted.
SELECTION CRITERIA
All RCTs and quasi-RCTs examining the efficacy of SSRIs compared with placebo for OCD in adults were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Selection of studies and data extraction were carried out by two review authors independently, and quality assessment of studies was undertaken. Data analysis was conducted using Review Manager software. Summary measures were produced using the weighted mean difference (WMD) for continuous data and relative risk (RR) for dichotomous data, with 95% confidence intervals (CI). SSRIs were examined as an overall group of drugs, and as individual drugs.
MAIN RESULTS
Seventeen studies were included in the review, involving 3097 participants. Based on all 17 studies, SSRIs as a group were more effective than placebo in reducing the symptoms of OCD between 6 and 13 weeks post-treatment, measured using the Yale-Brown Obsessive Compulsive Scale (YBOCS) (WMD -3.21, 95% CI -3.84 to -2.57). The WMD for individual SSRI drugs were similar and not statistically different. Based on 13 studies (2697 participants), SSRIs were more effective than placebo in achieving clinical response at post-treatment (RR 1.84, 95% CI 1.56 to 2.17). The pooled RR was shown to be similar between individual SSRI drugs. Although reported adverse effects data were more limited, with few exceptions, the overall and individual adverse effects for the different SSRIs were always worse than for placebo and, in the majority of cases, the difference was statistically significant. Nausea, headache and insomnia were always reported amongst the most common adverse effects in trials of each of the drugs.
AUTHORS' CONCLUSIONS
SSRIs are more effective than placebo for OCD, at least in the short-term, although there are differences between the adverse effects of individual SSRI drugs. The longer term efficacy and tolerability of different SSRI drugs for OCD has yet to be established.
Topics: Humans; Obsessive-Compulsive Disorder; Placebos; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 18253995
DOI: 10.1002/14651858.CD001765.pub3 -
BMJ (Clinical Research Ed.) Oct 2004
Topics: Evidence-Based Medicine; Humans; Pain; Placebos; Treatment Outcome
PubMed: 15499085
DOI: 10.1136/bmj.329.7472.927 -
British Medical Journal (Clinical... Mar 1984
Topics: Humans; Placebos; Psychotherapy
PubMed: 6423090
DOI: 10.1136/bmj.288.6420.809 -
JAMA Psychiatry Jan 2022Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug effects; however, the association of PRI periods with study outcomes remains unclear. This is concerning given the costs of PRI periods to patients and investigators.
OBJECTIVE
To examine the association of the use of PRI periods with the placebo response, drug response, and drug-placebo difference among RCTs of antidepressants.
DATA SOURCES
MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO, as well as repositories of unpublished studies, were systematically searched up to July 2021.
STUDY SELECTION
Included studies were double-blind, placebo-controlled RCTs of antidepressant medication among adults with depressive disorders.
DATA EXTRACTION AND SYNTHESIS
Data were extracted into a coding sheet, including the characteristics of studies, the characteristics of PRI periods, and the outcomes of studies.
MAIN OUTCOMES AND MEASURES
Study outcomes were the primary depression symptom measure reported by the RCT. These outcomes were used to calculate effect sizes (Hedges g) of the within-group drug response and placebo response as well as the drug-placebo difference. Random-effects meta-analysis was used to calculate effect sizes, and subgroup analyses were used to compare outcomes depending on use of PRI periods.
RESULTS
A total of 347 trials (representing 89 183 participants) were included; 174 studies (50%) reported using a single-blind PRI period. Response outcome data were available for 189 studies. Studies using PRI periods reported a smaller placebo response (g = 1.05 [95% CI, 0.98-1.11]; I2 = 82%) than studies that did not use a PRI period (g = 1.15 [95% CI, 1.09-1.21]; I2 = 81%; P = .02). Subgroup analysis showed a larger drug response size among studies that did not use a PRI period (g = 1.55 [95% CI, 1.49-1.61]; I2 = 85%) than those that did use a PRI period (g = 1.42 [95% CI, 1.36-1.48]; I2 = 81%; P = .001). The drug-placebo difference did not differ by use of PRI periods (g = 0.33 [95% CI, 0.29-0.38]; I2 = 47% for use of a PRI period vs g = 0.34 [95% CI, 0.30-0.38]; I2 = 54% for no use of PRI periods; P = .92). The likelihood of response to drug vs placebo also did not differ between studies that used a PRI period (odds ratio, 1.89 [95% CI, 1.76-2.03]) and those that did not use a PRI period (odds ratio, 1.77 [95% CI, 1.65-1.89]; P = .18).
CONCLUSIONS AND RELEVANCE
This study suggests that RCTs using PRI periods yield smaller within-group changes across both placebo and drug groups compared with RCTs without PRI periods. The reduction in effect size across groups was equivalent in magnitude. Consequently, PRI studies do not observe larger drug-placebo differences, suggesting that they do not increase trial sensitivity. As such, given the resources and probable deception required and risk to external validity, the practice of using PRI periods in RCTs of antidepressants should be ended.
Topics: Antidepressive Agents; Humans; Placebos; Randomized Controlled Trials as Topic; Single-Blind Method
PubMed: 34757405
DOI: 10.1001/jamapsychiatry.2021.3204 -
Medecine Sciences : M/S 2019A placebo drug is defined as a treatment without any specific pharmacological efficacy, that works when the patient thinks to receive an active treatment, through a... (Review)
Review
A placebo drug is defined as a treatment without any specific pharmacological efficacy, that works when the patient thinks to receive an active treatment, through a psychological and physiological mechanism. This study aimed to evaluate the use of placebo in French hospitals, in Polyvalent Medicine units. A questionnaire comprising 15 items was sent to 372 units. The analysis of 153 responses was conducted from dynamic crosstabs in Excel and using the R software available online. The survey confirmed that the use of placebos in hospital is frequent, with nearly 2/3 of professionals answering the questionnaire declared to use it. The oral capsule is the most commonly used form. Placebo is mainly administered at night, in case of pain, insomnia or anxiety, to so-called "difficult" patients. Placebo is not always given after medical prescription. In most cases, patients are not informed that they receive a placebo. The majority of professionals believed in the placebo effect but considered to be insufficiently informed and trained in the use of placebo in current practice. Although the placebo effect is now demonstrated, ethical and legal considerations recommend placebo treatment only on medical prescription, with the prior information of the patient. The placebo could be used as complementary therapy to conventional treatment in the cases of this therapeutic effectiveness has been demonstrated. Professionals should be trained in the use of placebo in order to avoid nocebo effect and potentiate beneficial effects of placebo.
Topics: Adult; Disclosure; Female; France; General Practice; Hospital Units; Hospitals; Humans; Male; Morals; Physician-Patient Relations; Placebo Effect; Placebos
PubMed: 31532380
DOI: 10.1051/medsci/2019127 -
Clinical Interventions in Aging 2018Placebo analgesia refers to a perceived reduction in pain intensity following the administration of a simulated or otherwise medically ineffective treatment. Previous...
PURPOSE
Placebo analgesia refers to a perceived reduction in pain intensity following the administration of a simulated or otherwise medically ineffective treatment. Previous studies have shown that many factors can influence the magnitude of placebo analgesia. However, few investigations have examined the effect of age on placebo analgesia, and none have done it in the context of electrotherapeutic interventions. The objective of this study is to compare the placebo response induced by sham transcutaneous electrical nerve stimulation (TENS) between young and older individuals, using an experimental heat-pain paradigm.
PATIENTS AND METHODS
Twenty-two young (21-39 years) and 22 older (58-76 years) healthy adults participated in this comparative study. Experimental heat pain was evoked with a thermode (2-min stimulation at a constant individually adjusted temperature) applied on the lumbar region. Participants were asked to evaluate the intensity of their pain using a computerized visual analog scale. Experimental pain was induced before and after an unconditioned placebo intervention (placebo TENS) applied for 25 min.
RESULTS
In young individuals, no significant pain reductions were noted, whereas in older individuals, a statistically significant pain reduction was observed after the placebo stimulation (<0.01). Between-group analyses revealed that placebo analgesia was greater in older individuals (40% pain reduction) compared with young individuals (15% pain reduction) (<0.05). However, sham TENS increased heat-pain thresholds in the young group (<0.01), but not in the older group (=0.43).
CONCLUSION
Our results indicate that placebo analgesia is influenced by age, with older individuals showing larger placebo analgesia than young adults. Although these results should be confirmed in clinical pain populations, the current observations bear potentially important consequences for the design of future placebo-controlled trials and for healthcare professionals working with elderly patients.
Topics: Adult; Age Factors; Aged; Analgesia; Female; Humans; Male; Middle Aged; Pain; Pain Management; Pain Measurement; Placebos; Research Design; Transcutaneous Electric Nerve Stimulation
PubMed: 29535508
DOI: 10.2147/CIA.S152906