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Neuroscience and Biobehavioral Reviews Jun 2020Placebo and nocebo effects can influence somatic symptoms such as pain. For itch and other dermatological symptoms these effects have been far less investigated. This... (Review)
Review
Placebo and nocebo effects can influence somatic symptoms such as pain. For itch and other dermatological symptoms these effects have been far less investigated. This review systematically integrates evidence from both animal (mainly rodents) and human trials on placebo and nocebo effects in itch, itch-related symptoms and conditions of the skin and mucous membranes, and related immune outcomes (e.g., histamine). Thirty-one animal studies, and fifty-five human studies (k = 21 healthy participants, k = 34 patients) were included. Overall, studies consistently show that placebo and nocebo effects can be induced by various methods (e.g., suggestions, conditioning and social cues), despite high heterogeneity across studies. Effects of suggestions were found consistently across subjective and behavioral parameters (e.g., itch and scratching in humans), whereas conditioning was likely to impact physiological parameters under certain conditions (e.g., conditioning of histamine levels in stressed rodents). Brain areas responsible for itch processing were associated with nocebo effects. Future research may investigate how variations in methods impact placebo and nocebo effects, and whether all symptoms and conditions can be influenced equally.
Topics: Animals; Cues; Humans; Nocebo Effect; Pain; Placebo Effect; Pruritus; Suggestion
PubMed: 32240668
DOI: 10.1016/j.neubiorev.2020.03.025 -
The Cochrane Database of Systematic... Jan 2021Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap. However, the diet is very restrictive and unpalatable and can be difficult to follow. A deficiency of the amino acid tyrosine has been suggested as a cause of some of the neuropsychological problems exhibited in phenylketonuria. Therefore, this review aims to assess the efficacy of tyrosine supplementation for phenylketonuria. This is an update of previously published versions of this review.
OBJECTIVES
To assess the effects of tyrosine supplementation alongside or instead of a phenylalanine-restricted diet for people with phenylketonuria, who commenced on diet at diagnosis and either continued on the diet or relaxed the diet later in life. To assess the evidence that tyrosine supplementation alongside, or instead of a phenylalanine-restricted diet improves intelligence, neuropsychological performance, growth and nutritional status, mortality rate and quality of life.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register which is comprised of references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional studies were identified from handsearches of the Journal of Inherited Metabolic Disease (from inception in 1978 to 1998). The manufacturers of prescribable dietary products used in the treatment of phenylketonuria were also contacted for further references. Date of the most recent search of the Group's Inborn Errors of Metabolism Trials Register: 07 December 2020.
SELECTION CRITERIA
All randomised or quasi-randomised trials investigating the use of tyrosine supplementation versus placebo in people with phenylketonuria in addition to, or instead of, a phenylalanine-restricted diet. People treated for maternal phenylketonuria were excluded.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the trial eligibility, methodological quality and extracted the data.
MAIN RESULTS
Six trials were found, of which three trials reporting the results of a total of 56 participants, were suitable for inclusion in the review. The blood tyrosine concentrations were significantly higher in the participants receiving tyrosine supplements than those in the placebo group, mean difference 23.46 (95% confidence interval 12.87 to 34.05). No significant differences were found between any of the other outcomes measured. The trials were assessed as having a low to moderate risk of bias across several domains.
AUTHORS' CONCLUSIONS
From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice. Further randomised controlled studies are required to provide more evidence. However, given this is not an active area of research, we have no plans to update this review in the future.
Topics: Dietary Supplements; Humans; Intelligence; Neuropsychological Tests; Phenylalanine; Phenylketonurias; Placebos; Randomized Controlled Trials as Topic; Tyrosine
PubMed: 33427303
DOI: 10.1002/14651858.CD001507.pub4 -
Frontiers in Psychology 2014Predicting who responds to placebo treatment-and under which circumstances-has been a question of interest and investigation for generations. However, the literature is... (Review)
Review
OBJECTIVE
Predicting who responds to placebo treatment-and under which circumstances-has been a question of interest and investigation for generations. However, the literature is disparate and inconclusive. This review aims to identify publications that provide high quality data on the topic of placebo response (PR) prediction.
METHODS
To identify studies concerned with PR prediction, independent searches were performed in an expert database (for all symptom modalities) and in PubMed (for pain only). Articles were selected when (a) they assessed putative predictors prior to placebo treatment and (b) an adequate control group was included when the associations of predictors and PRs were analyzed.
RESULTS
Twenty studies were identified, most with pain as dependent variable. Most predictors of PRs were psychological constructs related to actions, expected outcomes and the emotional valence attached to these events (goal-seeking, self-efficacy/-esteem, locus of control, optimism). Other predictors involved behavioral control (desire for control, eating restraint), personality variables (fun seeking, sensation seeking, neuroticism), or biological markers (sex, a single nucleotide polymorphism related to dopamine metabolism). Finally, suggestibility and beliefs in expectation biases, body consciousness, and baseline symptom severity were found to be predictive.
CONCLUSIONS
While results are heterogeneous, some congruence of predictors can be identified. PRs mainly appear to be moderated by expectations of how the symptom might change after treatment, or expectations of how symptom repetition can be coped with. It is suggested to include the listed constructs in future research. Furthermore, a closer look at variables moderating symptom change in control groups seems warranted.
PubMed: 25324797
DOI: 10.3389/fpsyg.2014.01079 -
Neurogastroenterology and Motility Feb 2023Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response.
METHODS
We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined.
KEY RESULTS
We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms.
CONCLUSIONS AND INFERENCES
The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
Topics: Adult; Humans; Dyspepsia; Placebo Effect; Treatment Outcome
PubMed: 36168188
DOI: 10.1111/nmo.14474 -
Frontiers in Pain Research (Lausanne,... 2021Fibromyalgia (FM) is a chronic primary pain condition, associated with widespread musculoskeletal pain, disturbed sleep, fatigue, cognitive dysfunction, and a range of...
Fibromyalgia (FM) is a chronic primary pain condition, associated with widespread musculoskeletal pain, disturbed sleep, fatigue, cognitive dysfunction, and a range of comorbid conditions such as irritable bowel syndrome, and depression. Despite its high prevalence of 2% in the general population, FM continues to pose scientific and clinical challenges in definition, etiology, and day-to-day management. In terms of treatment, FM can be treated with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs). Patients with FM and other chronic primary pain syndromes are known to experience substantial and clinically relevant placebo effects. An update of the placebo responses for various outcomes in the FM population and especially a discussion about clinical implications is therefore needed. We used data from a large data pool that includes randomized controlled trials (RCTs) examining within-placebo mean change scores of baseline vs. follow-up assessments in FM trials of SSRIs and SNRIs. The primary outcomes were pain, functional disability, and depression and using different scales. We assessed heterogeneity of included trials. A total of 29 RCTs with = 8,453 patients suffering from FM were included in our analysis. Within-placebo mean change scores of baseline vs. follow-up assessments were large for pain (mean change = 2.31, 95% CI: 0.42-4.21, = 0.017), functional disability (mean change = 3.31, 95% CI: 2.37-4.26, < 0.000), and depression (mean change = 1.55, 95% CI: 0.92-2.18, < 0.000). Heterogeneity was found to be large for all outcomes. Our results provide preliminary evidence that placebo responses, which also consist of non-specific effects, might play a role in the treatment of FM. Furthermore, we highlight limitations of our analyses and make suggestions for future studies.
PubMed: 35295427
DOI: 10.3389/fpain.2021.750523 -
The Cochrane Database of Systematic... Sep 2017It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors influencing placebo rates may lead to more informed clinical trial design.
OBJECTIVES
A systematic review and meta-analysis was conducted to evaluate placebo response and remission rates in RCTs evaluating UC treatments in adult patients.
SEARCH METHODS
Electronic databases (i.e. MEDLINE, EMBASE, and CENTRAL) were searched from inception to 1 March 2017 with no language restrictions applied. Reference lists and conference proceedings of major gastroenterology meetings were also handsearched to identify additional studies.
SELECTION CRITERIA
Placebo-controlled RCTs of adult patients with UC treated with corticosteroids, aminosalicylates, immunosuppressives or biologics were eligible, provided enrolment and outcome assessment was conducted using the Ulcerative Colitis Disease Activity Index (UCDAI) or the Mayo Clinic Score. The minimum trial duration was two weeks for induction trials and four months maintenance trials.
DATA COLLECTION AND ANALYSIS
Pairs of authors independently determined study eligibility and extracted data with any disagreements resolved through consensus. Outcomes of interest included the proportion of patients with clinical response and remission. Trial characteristics such as the design, participant demographics and disease history, interventions, and enrolment and assessment criteria were also recorded. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tool. Pooled placebo response and remission rates and 95% confidence intervals (95% CI) were calculated using a binomial normal model for proportions. Induction of remission and maintenance studies were pooled separately. The impact of study-level characteristics on placebo response and remission rates was investigated using mixed-effects meta-regression analyses with logits of event rates as the outcome variables. An assessment of pooled placebo rates over time was conducted using a cumulative meta-analysis based on date of publication. Publication bias was examined using funnel plots.
MAIN RESULTS
The screening process identified 61 included studies which encompass 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). For induction trials, the pooled estimate of placebo response was 33% (95% CI 30% to 36%) while the pooled estimate of placebo remission was 12% (95% CI 9% to 15%). For maintenance trials, the pooled estimate of placebo response was 23% (95% CI 19% to 28%) while the pooled estimate of placebo remission was 17% (95% CI 10% to 27%).Studies enrolling patients with more active disease confirmed objectively by endoscopy were associated with significantly lower placebo remission and response rates than trials enrolling patients with less active disease (27% versus 4%, OR 2.60, 95% CI 1.25 to 5.42, P = 0.01 for UCDAI endoscopy sub score ≥1 versus ≥ 2 for remission; and 27% versus 4%, OR 1.70, 95% CI 1.02 to 2.82, P = 0.02 for UCDAI endoscopy sub score greater than or equal to one versus greater than or equal to two for response). With respect to drug class, the lowest placebo response and remission rates were observed in trials evaluating corticosteroids (23%; 95% CI 19 to 29%, and 5%; 95% CI 2 to 11%, respectively). Trials of biologics had the highest placebo response rate (35%; 95% CI 30 to 41%), while trials evaluating aminosalicylates had the highest placebo remission rate (18%; 95% CI 12 to 24%). Disease duration of greater than five years prior to enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years (29% versus 47%, respectively; OR 0.54, 95% CI 0.32 to 0.92, P = 0.02). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility (37% versus 32%, respectively; OR 1.70, 95% CI 1.02 to 2.82, P = 0.02). Finally, the time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with a 6% increase in the placebo remission rate (OR 1.06, 95% CI 1.02 to 1.10, P = 0.01).Cumulative meta-analysis indicated a consistent increase in the placebo response rate from 1987 to 2007 (from 13% to 33%), although rates have remained constant from 2008 to 2015 (32% to 34%). Similarly, placebo remission rates increased from 1987 to 2007 (5% to 14%) but have remained constant from 2008 to 2015 (12 to 14%). On meta-regression, there were no statistically significant differences between the 1987-2007 and 2008-2015 point estimates for both response (P = 0.81) and remission (P = 0.32).
AUTHORS' CONCLUSIONS
Placebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, class of agent, disease duration, and the time point at which the primary outcome was measured. These observations have important implications for the design and conduct of future clinical trials in UC and will help researchers design trials, determine required sample sizes and also provide useful information about trial design features which should be considered when planning new trials.
Topics: Adult; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Biological Products; Colitis, Ulcerative; Gastrointestinal Hemorrhage; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Placebo Effect; Randomized Controlled Trials as Topic; Rectum
PubMed: 28886205
DOI: 10.1002/14651858.CD011572.pub2 -
The Cochrane Database of Systematic... Apr 2018Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear... (Review)
Review
BACKGROUND
Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear whether antidepressants are effective for the prevention of postnatal depression and little is known about possible adverse effects for the mother and infant, particularly during breastfeeding. This is an update of a Cochrane Review last published in 2005.
OBJECTIVES
To assess the effectiveness of antidepressant medication for the prevention of postnatal depression, in comparison with any other treatment, placebo or standard care.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR ‒ both Studies and References), CENTRAL (Wiley), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), on 13 February 2018. We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov on 13 February 2018 to identify any additional unpublished or ongoing studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of initiation of antidepressants (alone or in combination with another treatment), compared with any other treatment, placebo or standard care for the prevention of postnatal depression among women who were either pregnant or had given birth in the previous six weeks and were not currently depressed at baseline.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We requested missing information from investigators wherever possible and sought data to allow intention-to-treat analyses.
MAIN RESULTS
Two trials including a total of 81 participants fulfilled the inclusion criteria for this review. All participants in both studies had a history of postnatal depression and were not taking antidepressant medication at baseline. Both trials were conducted by the same research group. Risk of bias was low or unclear in most domains for both studies. We were unable to perform a meta-analysis due to the small number of studies.One study compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression. In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (RR 0.96, 95% CI 0.36 to 2.59, very low quality evidence) in the first 17 weeks postpartum. One woman taking nortriptyline developed mania; and one side effect, constipation, was more common among women taking nortriptyline than those taking placebo.The second study compared sertraline with placebo. In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (RR 0.14, 95% CI 0.02 to 1.07, very low quality evidence). One woman taking sertraline had a hypomanic episode. Two side effects (dizziness and drowsiness) were more common among women taking sertraline than women taking placebo.Conclusions are limited by the small number of studies, small sample sizes and incomplete outcome data due to study drop-out which may have led to bias in the results. We have assessed the certainty of the evidence as very low, based on the GRADE system. No data were available on secondary outcomes of interest including child development, the mother‒infant relationship, breastfeeding, maternal daily functioning, family relationships or maternal satisfaction.
AUTHORS' CONCLUSIONS
Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.
Topics: Antidepressive Agents; Depression, Postpartum; Female; Humans; Nortriptyline; Placebos; Randomized Controlled Trials as Topic; Sertraline
PubMed: 29669175
DOI: 10.1002/14651858.CD004363.pub3 -
The Cochrane Database of Systematic... Dec 2017Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of a review published in 2013.
OBJECTIVES
To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain.
SEARCH METHODS
On 21 November 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We searched the Chinese Biomedical Retrieval System (January 1978 to November 2016). We searched the US National Institutes of Health (NIH) databases and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials in January 2017, and we wrote to the companies who make oxcarbazepine and to pain experts requesting additional information.
SELECTION CRITERIA
All RCTs and randomised cross-over studies of oxcarbazepine for the treatment of people of any age or sex with any neuropathic pain were eligible. We planned to include trials of oxcarbazepine compared with placebo or any other intervention with a treatment duration of at least six weeks, regardless of administration route and dose.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Five multicentre, randomised, placebo-controlled, double-blind trials with a total of 862 participants were eligible for inclusion in this updated review. Three trials involved participants with painful diabetic peripheral neuropathy (DPN) (n = 634), one included people with neuropathic pain due to radiculopathy (n = 145), and one, which was newly identified at this update, involved participants with peripheral neuropathic pain of mixed origin (polyneuropathy, peripheral nerve injury or postherpetic neuralgia) (n = 83). Some studies did not report all outcomes of interest. For painful DPN, compared to the baseline, the proportion of participants who reported at least a 50% or 30% reduction of pain scores after 16 weeks of treatment in the oxcarbazepine group versus the placebo group were: at least 50% reduction: 34.8% with oxcarbazepine versus 18.2% with placebo (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.08 to 3.39, number of people needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 41); and at least 30% reduction: 44.9% with oxcarbazepine versus 28.6% with placebo (RR 1.57, 95% CI 1.01 to 2.44; NNTB 6, 95% CI 3 to 114; n = 146). Both results were based on data from a single trial, since two trials that found little or no benefit did not provide data that could be included in a meta-analysis. Although these trials were well designed, incomplete outcome data and possible unblinding of participants due to obvious adverse effects placed the results at a high risk of bias. There was also serious imprecision and a high risk of publication bias. The radiculopathy trial reported no benefit for the outcome 'at least 50% pain relief' from oxcarbazepine. In mixed neuropathies, 19.3% of people receiving oxcarbazepine versus 4.8% receiving placebo had at least 50% pain relief. These small trials had low event rates and provided, at best, low-quality evidence for any outcome. The proportion of people with 'improved' or 'very much improved' pain was 45.9% with oxcarbazepine versus 30.1% with placebo in DPN (RR 1.46, 95% CI 1.13 to 1.88; n = 493; 2 trials; very-low-quality evidence) and 23.9% with oxcarbazepine versus 14.9% with placebo in radiculopathy (RR 1.61, 95% CI 0.81 to 3.20; n = 145).We found no trials in other types of neuropathic pain such as trigeminal neuralgia.Trial reports stated that most adverse effects were mild to moderate in severity. Based on moderate-quality evidence from the three DPN trials, serious adverse effects occurred in 8.3% with oxcarbazepine and 2.5% with placebo (RR 3.65, 95% CI 1.45 to 9.20; n = 634; moderate-quality evidence). The number needed to treat for an additional harmful (serious adverse effect) outcome (NNTH) was 17 (95% CI 11 to 42). The RR for serious adverse effects in the radiculopathy trial was 3.13 (95% CI 0.65 to 14.98, n = 145). The fifth trial did not provide data.More people withdrew because of adverse effects with oxcarbazepine than with placebo (DPN: 25.6% with oxcarbazepine versus 6.8% with placebo; RR 3.83, 95% CI 2.29 to 6.40; radiculopathy: 42.3% with oxcarbazepine versus 14.9% with placebo; RR 2.84, 95% CI 1.55 to 5.23; mixed neuropathic pain: 13.5% with oxcarbazepine versus 1.2% with placebo; RR 11.51, 95% CI 1.54 to 86.15).
AUTHORS' CONCLUSIONS
This review found little evidence to support the effectiveness of oxcarbazepine in painful diabetic neuropathy, neuropathic pain from radiculopathy and a mixture of neuropathies. Some very-low-quality evidence suggests efficacy but small trials, low event rates, heterogeneity in some measures and a high risk of publication bias means that we have very low confidence in the measures of effect. Adverse effects, serious adverse effects and adverse effects leading to discontinuation are probably more common with oxcarbazepine than placebo; however, the numbers of participants and event rates are low. More well-designed, multicentre RCTs investigating oxcarbazepine for various types of neuropathic pain are needed, and selective publication of studies or data should be avoided.
Topics: Analgesics, Non-Narcotic; Carbamazepine; Diabetic Neuropathies; Humans; Neuralgia; Numbers Needed To Treat; Oxcarbazepine; Radiculopathy; Randomized Controlled Trials as Topic
PubMed: 29199767
DOI: 10.1002/14651858.CD007963.pub3 -
Pain Nov 2023Observing someone experience pain relief or exacerbation after an intervention may induce placebo hypoalgesia or nocebo hyperalgesia. Understanding the factors that... (Meta-Analysis)
Meta-Analysis
Observing someone experience pain relief or exacerbation after an intervention may induce placebo hypoalgesia or nocebo hyperalgesia. Understanding the factors that contribute to these effects could help in the development of strategies for optimizing treatment of chronic pain conditions. We systematically reviewed and meta-analyzed the literature on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning (OL). A systematic literature search was conducted in the databases PubMed, PsycINFO, Web of Science, ScienceDirect, PsycARTICLES, Scopus, and Academic Search Ultimate. Twenty-one studies were included in the systematic review, 17 of which were suitable for meta-analysis (18 experiments; n = 764 healthy individuals). The primary end point was the standardized mean difference (SMD) for pain following placebo cues associated during OL with low vs high pain. Observational learning had a small-to-medium effect on pain ratings (SMD 0.44; 95% confidence interval [CI] 0.21-0.68; P < 0.01) and a large effect on pain expectancy (SMD 1.11; 95% CI 0.49-2.04; P < 0.01). The type of observation (in-person vs videotaped) modulated the magnitude of placebo hypoalgesia/nocebo hyperalgesia ( P < 0.01), whereas placebo type did not ( P = 0.23). Finally, OL was more effective when observers' empathic concern (but no other empathy-related factors) was higher ( r = 0.14; 95% CI 0.01-0.27; P = 0.03). Overall, the meta-analysis demonstrates that OL can shape placebo hypoalgesia and nocebo hyperalgesia. More research is needed to identify predictors of these effects and to study them in clinical populations. In the future, OL could be an important tool to help maximize placebo hypoalgesia in clinical settings.
Topics: Humans; Hyperalgesia; Nocebo Effect; Pain; Learning; Pain Perception; Placebo Effect
PubMed: 37326688
DOI: 10.1097/j.pain.0000000000002943 -
The Cochrane Database of Systematic... Sep 2020This is the second update of this systematic review. High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is the second update of this systematic review. High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a link between hyperuricaemia and hypertension. Hyperuricaemia affects 25% to 40% of those with untreated hypertension; a much lower prevalence has been reported in those with normotension or in the general population. However, whether lowering serum uric acid (UA) might lower blood pressure (BP), is an unanswered question.
OBJECTIVES
To determine whether UA-lowering agents reduce BP in people with primary hypertension or prehypertension, compared with placebo.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to May 2020: the Cochrane Hypertension Specialised Register, CENTRAL 2018, Issue 12, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS (1982 to May 2020), and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language or date restrictions.
SELECTION CRITERIA
To be included in this updated review, the studies had to meet the following criteria: 1) randomised or quasi-randomised, with a group assigned to receive a UA-lowering agent and another group assigned to receive placebo; 2) double-blind, single-blind, or open-label; 3) parallel or cross-over trial design; 4) cross-over trials had to have a washout period of at least two weeks; 5) minimum treatment duration of four weeks; 6) participants had to have a diagnosis of essential hypertension or prehypertension plus hyperuricaemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men, and 5.5 mg/dL in children or adolescents); 7) outcome measures included change in 24-hour ambulatory systolic or diastolic BP, or both; or clinic-measured systolic or diastolic BP, or both.
DATA COLLECTION AND ANALYSIS
The two review authors independently collected the data using a data extraction form, and resolved any disagreements via discussion. We assessed risk of bias using the Cochrane 'Risk of bias' tool. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
In this review update, we screened 722 records, selected 26 full-text reports for evaluation. We identified no ongoing studies and did not add any new studies. We included three randomised controlled trials (RCTs), enrolling 211 people with hypertension or prehypertension, plus hyperuricaemia. Low-certainty evidence from three RCTs found inconclusive results between those who received UA-lowering drugs and placebo, in 24-hour ambulatory systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic BP (-3.9 mmHg, 95% CI -9.2 to 1.4). Low-certainty evidence from two RCTs found that UA-lowering drugs reduced clinic-measured systolic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but results for clinic-measured diastolic BP were inconclusive (-6.45 mmHg, 95% CI -13.60 to 0.70). High-certainty evidence from three RCTs found that serum UA levels were reduced by 3.1 mg/dL (95% CI 2.4 to 3.8) in the participants that received UA-lowering drugs. Low-certainty evidence from three RCTs found inconclusive results regarding the occurrence of adverse events between those who received UA-lowering drugs and placebo (RR 1.86, 95% CI 0.43 to 8.10).
AUTHORS' CONCLUSIONS
In this updated Cochrane Review, the current RCT data are insufficient to know whether UA-lowering therapy lowers BP. More studies are needed.
Topics: Adolescent; Adult; Allopurinol; Blood Pressure; Child; Humans; Hypertension; Hyperuricemia; Patient Dropouts; Placebos; Prehypertension; Randomized Controlled Trials as Topic; Uricosuric Agents
PubMed: 32877573
DOI: 10.1002/14651858.CD008652.pub4