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The Cochrane Database of Systematic... Jan 2019This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to nervous tissue). Antiepileptic drugs have long been used in pain management. Pregabalin is an antiepileptic drug used in management of chronic pain conditions.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of pregabalin for chronic neuropathic pain in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from January 2009 to April 2018, online clinical trials registries, and reference lists.
SELECTION CRITERIA
We included randomised, double-blind trials of two weeks' duration or longer, comparing pregabalin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality and biases. Primary outcomes were: at least 30% pain intensity reduction over baseline; much or very much improved on the Patient Global Impression of Change (PGIC) Scale (moderate benefit); at least 50% pain intensity reduction; or very much improved on PGIC (substantial benefit). We calculated risk ratio (RR) and number needed to treat for an additional beneficial (NNTB) or harmful outcome (NNTH). We assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included 45 studies lasting 2 to 16 weeks, with 11,906 participants - 68% from 31 new studies. Oral pregabalin doses of 150 mg, 300 mg, and 600 mg daily were compared with placebo. Postherpetic neuralgia, painful diabetic neuropathy, and mixed neuropathic pain predominated (85% of participants). High risk of bias was due mainly to small study size (nine studies), but many studies had unclear risk of bias, mainly due to incomplete outcome data, size, and allocation concealment.Postherpetic neuralgia: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (50% vs 25%; RR 2.1 (95% confidence interval (CI) 1.6 to 2.6); NNTB 3.9 (3.0 to 5.6); 3 studies, 589 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (32% vs 13%; RR 2.5 (95% CI 1.9 to 3.4); NNTB 5.3 (3.9 to 8.1); 4 studies, 713 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (62% vs 24%; RR 2.5 (95% CI 2.0 to 3.2); NNTB 2.7 (2.2 to 3.7); 3 studies, 537 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (41% vs 15%; RR 2.7 (95% CI 2.0 to 3.5); NNTB 3.9 (3.1 to 5.5); 4 studies, 732 participants, moderate-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 16% versus 5.5%, 600 mg 25% versus 5.8%; dizziness 300 mg 29% versus 8.1%, 600 mg 35% versus 8.8%.Painful diabetic neuropathy: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (47% vs 42%; RR 1.1 (95% CI 1.01 to 1.2); NNTB 22 (12 to 200); 8 studies, 2320 participants, moderate-quality evidence), more had at least 50% pain intensity reduction (31% vs 24%; RR 1.3 (95% CI 1.2 to 1.5); NNTB 22 (12 to 200); 11 studies, 2931 participants, moderate-quality evidence), and more had PGIC much or very much improved (51% vs 30%; RR 1.8 (95% CI 1.5 to 2.0); NNTB 4.9 (3.8 to 6.9); 5 studies, 1050 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (63% vs 52%; RR 1.2 (95% CI 1.04 to 1.4); NNTB 9.6 (5.5 to 41); 2 studies, 611 participants, low-quality evidence), and more had at least 50% pain intensity reduction (41% vs 28%; RR 1.4 (95% CI 1.2 to 1.7); NNTB 7.8 (5.4 to 14); 5 studies, 1015 participants, low-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 11% versus 3.1%, 600 mg 15% versus 4.5%; dizziness 300 mg 13% versus 3.8%, 600 mg 22% versus 4.4%.Mixed or unclassified post-traumatic neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (48% vs 36%; RR 1.2 (1.1 to 1.4); NNTB 8.2 (5.7 to 15); 4 studies, 1367 participants, low-quality evidence), and more had at least 50% pain intensity reduction (34% vs 20%; RR 1.5 (1.2 to 1.9); NNTB 7.2 (5.4 to 11); 4 studies, 1367 participants, moderate-quality evidence). Somnolence (12% vs 3.9%) and dizziness (23% vs 6.2%) were more common with pregabalin.Central neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (44% vs 28%; RR 1.6 (1.3 to 2.0); NNTB 5.9 (4.1 to 11); 3 studies, 562 participants, low-quality evidence) and at least 50% pain intensity reduction (26% vs 15%; RR 1.7 (1.2 to 2.3); NNTB 9.8 (6.0 to 28); 3 studies, 562 participants, low-quality evidence). Somnolence (32% vs 11%) and dizziness (23% vs 8.6%) were more common with pregabalin.Other neuropathic pain conditions: Studies show no evidence of benefit for 600 mg pregabalin in HIV neuropathy (2 studies, 674 participants, moderate-quality evidence) and limited evidence of benefit in neuropathic back pain or sciatica, neuropathic cancer pain, or polyneuropathy.Serious adverse events, all conditions: Serious adverse events were no more common with placebo than with pregabalin 300 mg (3.1% vs 2.6%; RR 1.2 (95% CI 0.8 to 1.7); 17 studies, 4112 participants, high-quality evidence) or pregabalin 600 mg (3.4% vs 3.4%; RR 1.1 (95% CI 0.8 to 1.5); 16 studies, 3995 participants, high-quality evidence).
AUTHORS' CONCLUSIONS
Evidence shows efficacy of pregabalin in postherpetic neuralgia, painful diabetic neuralgia, and mixed or unclassified post-traumatic neuropathic pain, and absence of efficacy in HIV neuropathy; evidence of efficacy in central neuropathic pain is inadequate. Some people will derive substantial benefit with pregabalin; more will have moderate benefit, but many will have no benefit or will discontinue treatment. There were no substantial changes since the 2009 review.
Topics: Acute Disease; Adult; Analgesics; Chronic Disease; Diabetic Neuropathies; Dizziness; Humans; Neuralgia; Neuralgia, Postherpetic; Pain; Pregabalin; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 30673120
DOI: 10.1002/14651858.CD007076.pub3 -
Ophthalmic & Physiological Optics : the... Jul 2016The aim of this study was to systematically review the literature to investigate the link (if any) between vision and dizziness. (Review)
Review
PURPOSE
The aim of this study was to systematically review the literature to investigate the link (if any) between vision and dizziness.
METHODS
Medline, CINAHL, AMED, Web of Science and The Cochrane Library were searched with keywords chosen to find articles which investigated the causes of dizziness and considered vision as a possible trigger. Citation chaining of all included papers was performed in addition to the hand searching of all reference lists. Unpublished literature was identified using www.opengrey.eu. The review considered studies involving adults which link, measure or attempt to improve any aspect of vision in relation to dizziness.
RESULTS
Nine thousand six hundred and eighty one possible references were found, and the abstracts were screened independently by two reviewers to determine if they should be included in the study. Thirteen papers were found which investigated whether dizziness was linked to an assessment of vision. Visual impairment measures were crude and typically self-report, or Snellen visual acuity with little or no measurement details. Five studies found an independent link between dizziness and vision, five found a weak association (typically finding a link when univariate analyses were used, but not when multivariate analyses were used), and three found no association. Studies finding a strong link were usually cross-sectional with a large study population whereas those finding a weak association had relatively small numbers of participants. Studies which did not find an association used a broad definition of dizziness that included the term light-headedness, an unreliable Rosenbaum near visual acuity chart or an unusual categorisation of visual acuity.
CONCLUSIONS
This review suggests that dizziness (although likely not 'light-headedness') is linked with poor vision although further studies using more appropriate measures of vision are recommended.
Topics: Dizziness; Humans; Vision, Low; Visual Acuity
PubMed: 27255594
DOI: 10.1111/opo.12299 -
Brain Sciences Jul 2022Clinical manifestations of COVID-19 include symptoms of vertigo and dizziness, which is rather unsurprising, since SARS-CoV-2 neurotropism may inflict a broad spectrum... (Review)
Review
Clinical manifestations of COVID-19 include symptoms of vertigo and dizziness, which is rather unsurprising, since SARS-CoV-2 neurotropism may inflict a broad spectrum of neuropathic effects. The widespread nature of central and peripheral audiovestibular pathways suggests that there may be several probable pathophysiological mechanisms. The cytokine storm, CNS infiltration of the virus through ACE 2 receptors, and other systemic factors can be responsible for the significant number of COVID-19 patients reported to experience symptoms of vertigo and dizziness. In this paper, we present a systematic review of clinical studies reporting the detection of dizziness and vertigo as clinical manifestations of COVID-19 and discuss their etiopathogenesis.
PubMed: 35884754
DOI: 10.3390/brainsci12070948 -
The Cochrane Database of Systematic... Mar 2023Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing... (Review)
Review
BACKGROUND
Persistent postural-perceptual dizziness (PPPD) is a chronic balance disorder, which is characterised by subjective unsteadiness or dizziness that is worse on standing and with visual stimulation. The condition was only recently defined and therefore the prevalence is currently unknown. However, it is likely to include a considerable number of people with chronic balance problems. The symptoms can be debilitating and have a profound impact on quality of life. At present, little is known about the optimal way to treat this condition. A variety of medications may be used, as well as other treatments, such as vestibular rehabilitation. OBJECTIVES: To evaluate the benefits and harms of pharmacological interventions for persistent postural-perceptual dizziness (PPPD). SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 21 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with PPPD, which compared selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with either placebo or no treatment. We excluded studies that did not use the Bárány Society criteria to diagnose PPPD and studies that followed up participants for less than three months. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vestibular symptoms (assessed as a dichotomous outcome - improved or not improved), 2) change in vestibular symptoms (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) generic health-related quality of life and 6) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no studies that met our inclusion criteria.
AUTHORS' CONCLUSIONS
At present, there is no evidence from placebo-controlled randomised trials regarding pharmacological treatments - specifically SSRIs and SNRIs - for PPPD. Consequently, there is great uncertainty over the use of these treatments for this condition. Further work is needed to establish whether any treatments are effective at improving the symptoms of PPPD, and whether their use is associated with any adverse effects.
Topics: Adult; Humans; Selective Serotonin Reuptake Inhibitors; Dizziness; Serotonin and Noradrenaline Reuptake Inhibitors; Chronic Disease
PubMed: 36906836
DOI: 10.1002/14651858.CD015188.pub2 -
Journal of Clinical Medicine Mar 2023Dizziness and vertigo are among the most prevalent complaints in the elderly and have a major negative influence on (i) the perception of the quality of life; and (ii)... (Review)
Review
Dizziness and vertigo are among the most prevalent complaints in the elderly and have a major negative influence on (i) the perception of the quality of life; and (ii) the risk of falling. Due to population aging, particularly in wealthy nations, vertigo represents a growing issue and a serious public health concern. In order to approach the patient correctly and to offer the best treatment options, it is mandatory to identify vertigo's underlying causes. The aim of this paper was to identify the different etiologies of vertigo and possibly their frequency in the elderly population, by reviewing the scientific literature of the last decade (2012-2022). A systematic review was performed according to PRISMA guidelines, searching the Medline database from January 2012 through to December 2022. The search identified 1025 candidate papers, but after the application of specific selection criteria, only five were considered for further analysis. A total of 2148 elderly patients (60-90 y old) presenting with vertigo were reported in the selected papers. A total of 3404 conditions were identified as the cause of vertiginous symptoms, (some patients presented multiple etiologies). All major diagnoses were categorized into different subgroups: the most common origin of vertigo was represented by audio-vestibular disorders (28.4%), followed by cardiovascular (20.4%) and neurological diseases (15.1%). Furthermore, 9.1% of patients were diagnosed with psychiatric conditions, whilst ophthalmologic and musculoskeletal disorders accounted for 7.5% and 6.3% of the cases respectively. Medication adverse effects and metabolic-related diseases were also considered among the causes. For 3.4% of cases the etiology remains unclear. Conclusions: Audio-vestibular disorders represent the most frequent cause of vertigo in the elderly. The etiologies affecting the vertigo patient must be defined in order to identify potential life-threatening conditions, such as cardiovascular and neurological disorders, which according to the data of this review constitute the second and third common causes of vertigo. A multidisciplinary strategy, involving different specialists (such as ENTs, Neurologists, Cardiologists, Geriatricians) is recommended for the correct assessment of these disorders.
PubMed: 36983184
DOI: 10.3390/jcm12062182 -
The Cochrane Database of Systematic... Jan 2015This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2007 and previously updated in 2011.Unilateral peripheral vestibular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2007 and previously updated in 2011.Unilateral peripheral vestibular dysfunction (UPVD) can occur as a result of disease, trauma or postoperatively. The dysfunction is characterised by complaints of dizziness, visual or gaze disturbances and balance impairment. Current management includes medication, physical manoeuvres and exercise regimes, the latter known collectively as vestibular rehabilitation.
OBJECTIVES
To assess the effectiveness of vestibular rehabilitation in the adult, community-dwelling population of people with symptomatic unilateral peripheral vestibular dysfunction.
SEARCH METHODS
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The most recent search was 18 January 2014.
SELECTION CRITERIA
Randomised controlled trials of adults living in the community, diagnosed with symptomatic unilateral peripheral vestibular dysfunction. We sought comparisons of vestibular rehabilitation versus control (e.g. placebo), other treatment (non-vestibular rehabilitation, e.g. pharmacological) or another form of vestibular rehabilitation. Our primary outcome measure was change in the specified symptomatology (for example, proportion with dizziness resolved, frequency or severity of dizziness). Secondary outcomes were measures of function, quality of life and/or measure(s) of physiological status, where reproducibility has been confirmed and shown to be relevant or related to health status (for example, posturography), and adverse effects
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 39 studies involving 2441 participants with unilateral peripheral vestibular disorders in the review. Trials addressed the effectiveness of vestibular rehabilitation against control/sham interventions, medical interventions or other forms of vestibular rehabilitation. Non-blinding of outcome assessors and selective reporting were threats that may have biased the results in 25% of studies, but otherwise there was a low risk of selection or attrition bias.Individual and pooled analyses of the primary outcome, frequency of dizziness, showed a statistically significant effect in favour of vestibular rehabilitation over control or no intervention (odds ratio (OR) 2.67, 95% confidence interval (CI) 1.85 to 3.86; four studies, 565 participants). Secondary outcomes measures related to levels of activity or participation measured, for example, with the Dizziness Handicap Inventory, which also showed a strong trend towards significant differences between the groups (standardised mean difference (SMD) -0.83, 95% CI -1.02 to -0.64). The exception to this was when movement-based vestibular rehabilitation was compared to physical manoeuvres for benign paroxysmal positional vertigo (BPPV), where the latter was shown to be superior in cure rate in the short term (OR 0.19, 95% CI 0.07 to 0.49). There were no reported adverse effects.
AUTHORS' CONCLUSIONS
There is moderate to strong evidence that vestibular rehabilitation is a safe, effective management for unilateral peripheral vestibular dysfunction, based on a number of high-quality randomised controlled trials. There is moderate evidence that vestibular rehabilitation resolves symptoms and improves functioning in the medium term. However, there is evidence that for the specific diagnostic group of BPPV, physical (repositioning) manoeuvres are more effective in the short term than exercise-based vestibular rehabilitation; although a combination of the two is effective for longer-term functional recovery. There is insufficient evidence to discriminate between differing forms of vestibular rehabilitation.
Topics: Adult; Dizziness; Exercise Movement Techniques; Humans; Postural Balance; Randomized Controlled Trials as Topic; Sensation Disorders; Vertigo; Vestibular Diseases; Vestibule, Labyrinth
PubMed: 25581507
DOI: 10.1002/14651858.CD005397.pub4 -
The Journal of Laryngology and Otology Sep 2023Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Vestibular migraine is in the process of recognition as an individual clinical entity. At present, no guidelines exist for its management. This study aimed to conduct a systematic review and meta-analysis to determine the effectiveness of available prophylactic medication.
METHOD
literature search was performed using PubMed, Ovid and Embase databases. Qualitative and quantitative analysis were performed as well as risk of bias analysis. Meta-analysis for the mean differences for pre- and post-treatment impact based on Dizziness Handicap Inventory and Vertigo Symptom Scale were performed. Proportionate transformation meta-analysis for the successful event rate based on complete symptoms control was explored.
RESULTS
Thirteen publications were identified: 3 were randomised, controlled trials and 10 were non-randomised, controlled trials. Propranolol and venlafaxine improved the Vertigo Symptom Scale score by -13.31 points and -4.16 points, respectively, and the Dizziness Handicap Inventory score by -32.24 and -21.24, respectively. Only propranolol achieved statistically significant impact with 60 per cent of patients achieving complete symptom control.
CONCLUSION
Propranolol should be offered as the first-line treatment for vestibular migraine followed by venlafaxine. Amitriptyline, flunarizine and cinnarizine showed a trend for symptom improvement, but this was not statistically significant.
Topics: Humans; Dizziness; Propranolol; Venlafaxine Hydrochloride; Vertigo; Migraine Disorders
PubMed: 36200521
DOI: 10.1017/S0022215122001979 -
The Cochrane Database of Systematic... Jun 2016Vertigo is a symptom in which individuals experience a false sensation of movement. This type of dizziness is thought to originate in the inner ear labyrinth or its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vertigo is a symptom in which individuals experience a false sensation of movement. This type of dizziness is thought to originate in the inner ear labyrinth or its neural connections. It is a commonly experienced symptom and can cause significant problems with carrying out normal activities. Betahistine is a drug that may work by improving blood flow to the inner ear. This review examines whether betahistine is more effective than a placebo at treating symptoms of vertigo from different causes.
OBJECTIVES
To assess the effects of betahistine in patients with symptoms of vertigo from different causes.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. We also contacted manufacturers and researchers in the field. The date of the search was 21 September 2015.
SELECTION CRITERIA
We included randomised controlled trials of betahistine versus placebo in patients of any age with vertigo from any neurotological diagnosis in any settings.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Our primary outcome was the proportion of patients with reduction in vertigo symptoms (considering together the intensity, frequency and duration those symptoms).
MAIN RESULTS
We included 17 studies, with a total of 1025 participants; 12 studies were published (567 patients) and five were unpublished (458 patients). Sixteen studies including 953 people compared betahistine with placebo. All studies with analysable data lasted three months or less. The majority were at high risk of bias, but in some the risk of bias was unclear. One study, at high risk of bias, included 72 people with benign paroxysmal positional vertigo (BPPV) and compared betahistine with placebo; all patients also had particle repositioning manoeuvres. The studies varied considerably in terms of types of participants, their diagnoses, the dose of betahistine and the length of time it was taken for, the study methods and the way any improvement in vertigo symptoms was measured. Using the GRADE system, we judged the quality of evidence overall to be low for two outcomes (proportion of patients with improvement and proportion with adverse events).Pooled data showed that the proportion of patients reporting an overall reduction in their vertigo symptoms was higher in the group treated with betahistine than the placebo group: risk ratio (RR) 1.30, 95% confidence interval (CI) 1.05 to 1.60; 606 participants; 11 studies). This result should be interpreted with caution as the test for statistical heterogeneity as measured by the I(2) value was high.Adverse effects (mostly gastrointestinal symptoms and headache) were common but medically serious events in the study were rare and isolated: there was no difference in the frequency of adverse effects between the betahistine and placebo groups, where the rates were 16% and 15% respectively (weighted values, RR 1.03, 95% CI 0.76 to 1.40; 819 participants; 12 studies).Sixteen per cent of patients from both the betahistine and the placebo groups withdrew (dropped out) from the studies (RR 0.96, 95% CI 0.65 to 1.42; 481 participants; eight studies).Three studies looked at objective vestibular function tests as an outcome; the numbers of participants were small, techniques of measurement very diverse and reporting details sparse, so analysis of this outcome was inconclusive.We looked for information on generic quality of life and falls, but none of the studies reported on these outcomes.
AUTHORS' CONCLUSIONS
Low quality evidence suggests that in patients suffering from vertigo from different causes there may be a positive effect of betahistine in terms of reduction in vertigo symptoms. Betahistine is generally well tolerated with a low risk of adverse events. Future research into the management of vertigo symptoms needs to use more rigorous methodology and include outcomes that matter to patients and their families.
Topics: Benign Paroxysmal Positional Vertigo; Betahistine; Humans; Randomized Controlled Trials as Topic; Vertigo
PubMed: 27327415
DOI: 10.1002/14651858.CD010696.pub2 -
The Cochrane Database of Systematic... Oct 2016This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP.
OBJECTIVES
This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and Embase for relevant studies. We ran the searches for the original review in September 2011 and subsequent searches for this update up to April 2016. We sought additional studies from clinical trials databases and reference lists of retrieved papers.
SELECTION CRITERIA
We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions compared with placebo, another active treatment, or no treatment, in established PLP. We considered the following outcomes: change in pain intensity, function, sleep, depression or mood, quality of life, adverse events, treatment satisfaction, and withdrawals from the study.
DATA COLLECTION AND ANALYSIS
We independently assessed issues of study quality and extracted efficacy and adverse event data. Due to the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes, but attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results. We assessed clinical heterogeneity by making qualitative comparisons of the populations, interventions, outcomes/outcome measures, and methods.
MAIN RESULTS
We added only one new study with 14 participants to this updated review. We included a 14 studies (10 with low risk of bias and 4 with unclear risk of bias overall) with a total of 269 participants. We added another drug class, botulinum neurotoxins (BoNTs), in particular botulinum toxin A (BoNT/A), to the group of medications reviewed previously. Our primary outcome was change in pain intensity. Most studies did not report our secondary outcomes of sleep, depression or mood, quality of life, treatment satisfaction, or withdrawals from the study.BoNT/A did not improve phantom limb pain intensity during the six months of follow-up compared with lidocaine/methylprednisolone.Compared with placebo, morphine (oral and intravenous) was effective in decreasing pain intensity in the short term with reported adverse events being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems.The N-methyl D-aspartate (NMDA) receptor antagonists ketamine (versus placebo; versus calcitonin) and dextromethorphan (versus placebo), but not memantine, had analgesic effects. The adverse events of ketamine were more serious than placebo and calcitonin and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety.The results for gabapentin in terms of pain relief were conflicting, but combining the results favoured treatment group (gabapentin) over control group (placebo) (mean difference -1.16, 95% confidence interval -1.94 to -0.38; 2 studies). However, gabapentin did not improve function, depression score, or sleep quality. Adverse events experienced were somnolence, dizziness, headache, and nausea.Compared with an active control benztropine mesylate, amitriptyline was not effective in PLP, with dry mouth and dizziness as the most frequent adverse events based on one study.The findings for calcitonin (versus placebo; versus ketamine) and local anaesthetics (versus placebo) were variable. Adverse events of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes.
AUTHORS' CONCLUSIONS
Since the last version of this review, we identified another study that added another form of medical therapy, BoNTs, specifically BoNT/A, to the list of pharmacologic interventions being reviewed for clinical efficacy in phantom limb pain. However, the results of this study did not substantially change the main conclusions. The short- and long-term effectiveness of BoNT/A, opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anaesthetics for clinically relevant outcomes including pain, function, mood, sleep, quality of life, treatment satisfaction, and adverse events remain unclear. Based on a small study, BoNT/A (versus lidocaine/methylprednisolone) does not decrease phantom limb pain. Morphine, gabapentin, and ketamine demonstrate favourable short-term analgesic efficacy compared with placebo. Memantine and amitriptyline may not be effective for PLP. However, results must be interpreted with caution, as they were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, local anaesthetics, and dextromethorphan needs further clarification. Overall, the efficacy evidence for the reviewed medications is thus far inconclusive. Larger and more rigorous randomised controlled trials are needed for us to reach more definitive conclusions about which medications would be useful for clinical practice.
Topics: Analgesics, Opioid; Anesthetics; Anticonvulsants; Antidepressive Agents; Botulinum Toxins, Type A; Calcitonin; Humans; Neurotoxins; Phantom Limb; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 27737513
DOI: 10.1002/14651858.CD006380.pub3 -
The Cochrane Database of Systematic... Feb 2023Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. A number of pharmacological interventions have... (Review)
Review
BACKGROUND
Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. A number of pharmacological interventions have been used in the management of this condition, including betahistine, diuretics, antiviral medications and corticosteroids. The underlying cause of Ménière's disease is unknown, as is the way in which these treatments may work. The efficacy of these different interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear.
OBJECTIVES
To evaluate the benefits and harms of systemic pharmacological interventions versus placebo or no treatment in people with Ménière's disease.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable Ménière's disease comparing betahistine, diuretics, antihistamines, antivirals or systemic corticosteroids with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 10 studies with a total of 848 participants. The studies evaluated the following interventions: betahistine, diuretics, antivirals and corticosteroids. We did not identify any evidence on antihistamines. Betahistine Seven RCTs (548 participants) addressed this comparison. However, we were unable to conduct any meta-analyses for our primary outcomes as not all outcomes were considered by every study, and studies that did report the same outcome used different time points for follow-up, or assessed the outcome using different methods. Therefore, we were unable to draw meaningful conclusions from the numerical results. Some data were available for each of our primary outcomes, but the evidence was low- or very low-certainty throughout. One study reported on the outcome 'improvement in vertigo' at 6 to ≤ 12 months, and another study reported this outcome at > 12 months. Four studies reported on the change in vertigo, but again all used different methods of assessment (vertigo frequency, or a global score of vertigo severity) or different time points. A single study reported on serious adverse events. Diuretics Two RCTs addressed this comparison. One considered the use of isosorbide (220 participants), and the other used a combination of amiloride hydrochloride and hydrochlorothiazide (80 participants). Again, we were unable to conduct any meta-analyses for our primary outcomes, as only one study reported on the outcome 'improvement in vertigo' (at 6 to ≤ 12 months), one study reported on change in vertigo (at 3 to < 6 months) and neither study assessed serious adverse events. Therefore, we were unable to draw meaningful conclusions from the numerical results. The evidence was all very low-certainty. Other pharmacological interventions We also identified one study that assessed antivirals (24 participants), and one study that assessed corticosteroids (16 participants). The evidence for these interventions was all very low-certainty. Again, serious adverse events were not considered by either study.
AUTHORS' CONCLUSIONS
The evidence for systemic pharmacological interventions for Ménière's disease is very uncertain. There are few RCTs that compare these interventions to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analyses of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.
Topics: Adult; Humans; Meniere Disease; Tinnitus; Betahistine; Adrenal Cortex Hormones; Vertigo; Diuretics; Histamine Antagonists
PubMed: 36827524
DOI: 10.1002/14651858.CD015171.pub2