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General Hospital Psychiatry 2022Caffeine has been purported to have anxiogenic and panicogenic properties, specifically salient in patients with panic disorder (PD). However, compilations of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Caffeine has been purported to have anxiogenic and panicogenic properties, specifically salient in patients with panic disorder (PD). However, compilations of the magnitude of the effect of caffeine on anxiety and panic attacks are lacking and potential dose-response relationships have not been examined.
OBJECTIVES
In the present systematic review and meta-analysis, we aimed to examine the acute effects of placebo-controlled caffeine challenge on occurrence of panic attacks and subjective anxiety in patients with PD and healthy controls (HC), including dose-response relationships.
METHODS
Systematic searches were performed in six databases. We included blinded placebo-controlled studies of acute caffeine challenge on panic attacks and/or subjective anxiety in adult patients with PD.
RESULTS
Of the 1893 identified articles, ten met our inclusion criteria. The 9 studies investigating panic attacks included 237 patients, of which 51.1% had a panic attack following caffeine, but none after placebo. Six of these studies compared 128 patients with 115 healthy controls (HC), finding that patients (53.9%) were more vulnerable than HC (1.7%) for panic attacks following caffeine (log RR: 3.47; 95% CI 2.06-4.87). Six studies investigated subjective anxiety in 121 patients and 111 HC following caffeine, with an overall effect indicating increased sensitivity to the anxiogenic effects of caffeine in the patient group (Hedges' g = 1.02 [95% CI: 0.09-1.96]). The restricted range of caffeine employed [400-750 mg] and few studies (3) not using 480 mg prevented any meaningful analysis of a dose-response relationship.
LIMITATIONS
Of the ten studies included, only 2 reported anxiety data for the placebo condition, precluding a proper meta-analysis comparing anxiogenic effects of caffeine and placebo. The restricted dose range used prevented assessment of dose-response relationships.
CONCLUSIONS
The results confirm that caffeine at doses roughly equivalent to 5 cups of coffee induces panic attacks in a large proportion of PD patients and highly discriminates this population from healthy adults. Caffeine also increases anxiety in PD patients as well as among healthy adults at these doses although the exact relationship between caffeine-induced anxiety and panic attacks remains uncertain. The results suggest that caffeine targets important mechanisms related to the pathophysiology of PD.
IMPLICATIONS
Future studies should employ a wider range of caffeine doses and investigate contributions of biological and psychological mechanisms underlying the anxiogenic and panicogenic effects of caffeine. In the clinic, patients with PD should be informed about the panicogenic and anxiogenic effects of caffeine, with the caveat that little is known regarding smaller doses than 480 mg. Registration. PROSPERO (www.crd.york.ac.uk/prospero) registration number CRD42019120220.
Topics: Adult; Anxiety; Anxiety Disorders; Caffeine; Humans; Panic Disorder
PubMed: 34871964
DOI: 10.1016/j.genhosppsych.2021.11.005 -
The Cochrane Database of Systematic... Sep 2022Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. This is an update of a review first... (Review)
Review
BACKGROUND
Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. This is an update of a review first published in 2010 and updated in 2013.
OBJECTIVES
To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults.
SEARCH METHODS
We updated our searches in the following databases to May 2022: the Cochrane Central Register of Controlled Trials (CENTRAL) via OvidSP, MEDLINE via OvidSP (from 1966), Embase via embase.com (from 1974), Physiotherapy Evidence Database (PEDro) (from 1929), CINAHL via EBSCO (from 2009), and the Chinese Biomedical Literature Database (CBM) (from 1978).
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs assessing the efficacy of chest physiotherapy for treating pneumonia in adults.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included two new trials in this update (540 participants), for a total of eight RCTs (974 participants). Four RCTs were conducted in the United States, two in Sweden, one in China, and one in the United Kingdom. The studies looked at five types of chest physiotherapy: conventional chest physiotherapy; osteopathic manipulative treatment (OMT, which includes paraspinal inhibition, rib raising, and myofascial release); active cycle of breathing techniques (which includes active breathing control, thoracic expansion exercises, and forced expiration techniques); positive expiratory pressure; and high-frequency chest wall oscillation. We assessed four trials as at unclear risk of bias and four trials as at high risk of bias. Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving mortality, but the certainty of evidence is very low (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.15 to 7.13; 2 trials, 225 participants; I² = 0%). OMT (versus placebo) may have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.43, 95% CI 0.12 to 1.50; 3 trials, 327 participants; I² = 0%). Similarly, high-frequency chest wall oscillation (versus no physiotherapy) may also have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.75, 95% CI 0.17 to 3.29; 1 trial, 286 participants). Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.93, 95% CI 0.56 to 1.55; 2 trials, 225 participants; I² = 85%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.60, 95% CI 0.29 to 1.23; 1 trial, 32 participants). OMT (versus placebo) may improve cure rate, but the certainty of evidence is very low (RR 1.59, 95% CI 1.01 to 2.51; 2 trials, 79 participants; I² = 0%). OMT (versus placebo) may have little to no effect on mean duration of hospital stay, but the certainty of evidence is very low (mean difference (MD) -1.08 days, 95% CI -2.39 to 0.23; 3 trials, 333 participants; I² = 50%). Conventional chest physiotherapy (versus no physiotherapy, MD 0.7 days, 95% CI -1.39 to 2.79; 1 trial, 54 participants) and active cycle of breathing techniques (versus no physiotherapy, MD 1.4 days, 95% CI -0.69 to 3.49; 1 trial, 32 participants) may also have little to no effect on duration of hospital stay, but the certainty of evidence is very low. Positive expiratory pressure (versus no physiotherapy) may reduce the mean duration of hospital stay by 1.4 days, but the certainty of evidence is very low (MD -1.4 days, 95% CI -2.77 to -0.03; 1 trial, 98 participants). Positive expiratory pressure (versus no physiotherapy) may reduce the duration of fever by 0.7 days, but the certainty of evidence is very low (MD -0.7 days, 95% CI -1.36 to -0.04; 1 trial, 98 participants). Conventional chest physiotherapy (versus no physiotherapy, MD 0.4 days, 95% CI -1.01 to 1.81; 1 trial, 54 participants) and OMT (versus placebo, MD 0.6 days, 95% CI -1.60 to 2.80; 1 trial, 21 participants) may have little to no effect on duration of fever, but the certainty of evidence is very low. OMT (versus placebo) may have little to no effect on the mean duration of total antibiotic therapy, but the certainty of evidence is very low (MD -1.07 days, 95% CI -2.37 to 0.23; 3 trials, 333 participants; I² = 61%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on duration of total antibiotic therapy, but the certainty of evidence is very low (MD 0.2 days, 95% CI -4.39 to 4.69; 1 trial, 32 participants). High-frequency chest wall oscillation plus fibrobronchoscope alveolar lavage (versus fibrobronchoscope alveolar lavage alone) may reduce the MD of intensive care unit (ICU) stay by 3.8 days (MD -3.8 days, 95% CI -5.00 to -2.60; 1 trial, 286 participants) and the MD of mechanical ventilation by three days (MD -3 days, 95% CI -3.68 to -2.32; 1 trial, 286 participants), but the certainty of evidence is very low. One trial reported transient muscle tenderness emerging after OMT in two participants. In another trial, three serious adverse events led to early withdrawal after OMT. One trial reported no adverse events after positive expiratory pressure treatment. Limitations of this review were the small sample size and unclear or high risk of bias of the included trials.
AUTHORS' CONCLUSIONS
The inclusion of two new trials in this update did not change the main conclusions of the original review. The current evidence is very uncertain about the effect of chest physiotherapy on improving mortality and cure rate in adults with pneumonia. Some physiotherapies may slightly shorten hospital stays, fever duration, and ICU stays, as well as mechanical ventilation. However, all of these findings are based on very low certainty evidence and need to be further validated.
Topics: Adult; Anti-Bacterial Agents; Humans; Physical Therapy Modalities; Pneumonia; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Therapy
PubMed: 36066373
DOI: 10.1002/14651858.CD006338.pub4 -
Sports Health 2017Taping is commonly used in the management of several musculoskeletal conditions, including patellofemoral pain syndrome (PFPS). Specific guidelines for taping are... (Review)
Review
CONTEXT
Taping is commonly used in the management of several musculoskeletal conditions, including patellofemoral pain syndrome (PFPS). Specific guidelines for taping are unknown.
OBJECTIVE
To investigate the efficacy of knee taping in the management of PFPS. Our hypothesis was that tension taping and exercise would be superior to placebo taping and exercise as well as to exercise or taping alone.
DATA SOURCES
The PubMed/MEDLINE, Cochrane, Rehabilitation and Sports Medicine Source, and CINAHL databases were reviewed for English-language randomized controlled trials (RCTs) evaluating the efficacy of various taping techniques that were published between 1995 and April 2015. Keywords utilized included taping, McConnell, kinesio-taping, kinesiotaping, patellofemoral pain, and knee.
STUDY SELECTION
Studies included consisted of RCTs (level 1 or 2) with participants of all ages who had anterior knee or patellofemoral pain symptoms and had received nonsurgical management using any taping technique.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 2.
DATA EXTRACTION
A checklist method was used to determine selection, performance, detection, and attrition bias for each article. A quality of evidence grading was then referenced using the validated PEDro database for RCTs. Three difference comparison groups were compared: tension taping and exercise versus placebo taping and exercise (group 1), placebo taping and exercise versus exercise alone (group 2), and tension taping and exercise versus taping alone (group 3).
RESULTS
Five RCTs with 235 total patients with multiple intervention arms were included. Taping strategies included McConnell and Kinesiotaping. Visual analog scale (VAS) scores indicated improvement in all 3 comparison groups (group 1: 91 patients, 39% of total, mean VAS improvement 44.9 [tension taping + exercise] vs 66 [placebo taping + exercise]; group 2: 56 patients, 24% of total, mean VAS improvement 66 [placebo taping + exercise] vs 47.6 [exercise alone]; and group 3: 112 patients, 48% of total, mean VAS improvement 44.9 [tension taping + exercise] vs 14.1 [taping alone]).
CONCLUSION
This systematic review supports knee taping only as an adjunct to traditional exercise therapy for PFPS; however, it does not support taping in isolation.
Topics: Athletic Performance; Athletic Tape; Exercise Therapy; Humans; Pain Measurement; Patellofemoral Pain Syndrome; Treatment Outcome
PubMed: 28617653
DOI: 10.1177/1941738117710938 -
Frontiers in Immunology 2023Tendinopathy is a growing global concern affecting many people, like athletes, workers, and the elderly. Despite its commonality among the sporting population, there is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tendinopathy is a growing global concern affecting many people, like athletes, workers, and the elderly. Despite its commonality among the sporting population, there is no practical clinical guideline for patellar tendinopathy (PT). Furthermore, there is conflicting evidence between clinical guidelines on shockwave therapy's application and clinical utility for Achilles tendinopathy (AT) and plantar fasciitis (PF). Thus, our aim of this study is to evaluate the evidence for shockwave therapy; to provide a Grading of Recommendation, Assessment, Development and Evaluation (GRADE) level of the evidence and effectiveness of shockwave therapy for patellar tendinopathy, Achilles tendinopathy, and Plantar fasciitis.
METHOD
Medical Literature Analysis and Retrieval System Online (Medline), Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro) and China National Knowledge Infrastructure database (CNKI) were searched to find relevant studies published before December 14, 2022.
RESULTS
Our study showed that for PT in the short term, extracorporeal shockwave therapy (ESWT) or ESWT + eccentric exercise (EE) has a negligible effect on pain and function compared to a placebo or placebo + EE. On the contrary, ESWT significantly affects pain compared to conservative treatment (CT). For AT, ESWT has a small inconclusive effect on pain and function in the short term compared to EE. On the other hand, a placebo outperformed ESWT in improving function for AT but not pain outcomes. PF showed that ESWT significantly affects short- and long-term pain and function. When ESWT was compared to other interventions such as low laser therapy (LLLT), corticosteroid injection (CSI), or CT, there was a small inconclusive effect on pain and function in the short term.
CONCLUSION
There is low-moderate evidence that ESWT has a negligible effect on pain and function for PT and AT. However, high-quality evidence suggests ESWT has a large effect on pain and function for PF.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396835, identifier CRD42023396835.
Topics: Aged; Humans; Achilles Tendon; Extracorporeal Shockwave Therapy; Fasciitis, Plantar; High-Energy Shock Waves; Musculoskeletal Diseases; Tendinopathy
PubMed: 37662911
DOI: 10.3389/fimmu.2023.1193835 -
The Cochrane Database of Systematic... Mar 2022Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed... (Review)
Review
BACKGROUND
Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment.
OBJECTIVES
To assess the effects of medication for reducing PTSD symptoms in adults with PTSD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020.
SELECTION CRITERIA
All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD.
DATA COLLECTION AND ANALYSIS
Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity.
MAIN RESULTS
We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis. For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence. For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events.
AUTHORS' CONCLUSIONS
The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amitriptyline; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Humans; Middle Aged; Mirtazapine; Paroxetine; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic; Young Adult
PubMed: 35234292
DOI: 10.1002/14651858.CD002795.pub3 -
European Journal of Pain (London,... Jan 2023Phantom limb pain (PLP) concerns >50% of amputees and has a negative impact on their rehabilitation, mental health and quality of life. Mirror therapy (MT) is a... (Review)
Review
Effect of mirror therapy in the treatment of phantom limb pain in amputees: A systematic review of randomized placebo-controlled trials does not find any evidence of efficacy.
BACKGROUND AND OBJECTIVE
Phantom limb pain (PLP) concerns >50% of amputees and has a negative impact on their rehabilitation, mental health and quality of life. Mirror therapy (MT) is a promising strategy, but its effectiveness remains controversial. We performed a systematic review to: (i) evaluate the effectiveness of MT versus placebo in reducing PLP, and (ii) determine MT effect on disability and quality of life.
DATABASES AND DATA TREATMENT
We selected randomized-controlled trials in five databases (Medline, Cochrane Library, CINAHL, PEDro and Embase) that included patients with unilateral lower or upper limb amputation and PLP and that compared the effects on PLP of MT versus a placebo technique. The primary outcome was PLP intensity changes and the secondary outcomes were PLP duration, frequency, patients' disability and quality of life.
RESULTS
Among the five studies included, only one reported a significant difference between the MT group and control group, with a positive MT effect at week 4. Only one study assessed MT effect on disability and found a significant improvement in the MT group at week 10 and month 6.
CONCLUSIONS
Our systematic review did not allow concluding that MT reduces PLP and disability in amputees. This lack of strong evidence is probably due to (i) the low methodological quality of the included studies, and (ii) the lack of statistical power. Future trials should include a higher number of patients, increase the number and frequency of MT sessions, have a long-term follow-up and improve the methodological quality.
SIGNIFICANCE
Recent meta-analyses concluded that MT is effective for reducing phantom limb pain. Conversely, the present systematic review that included only studies with the best level of evidence did not find any evidence about its effectiveness for this condition. We identified many ways to improve future randomized-controlled trials on this topic: increasing the number of participants, reducing the intra-group heterogeneity, using a suitable placebo and intensifying the MT sessions and frequency.
Topics: Humans; Phantom Limb; Quality of Life; Mirror Movement Therapy; Amputees; Pain Management; Randomized Controlled Trials as Topic
PubMed: 36094758
DOI: 10.1002/ejp.2035 -
Frontiers in Bioscience (Landmark... Aug 2021: Smart drugs are among the most common drugs used by students. It is estimated that they are second in incidence after cannabis. Although they are usually used for... (Review)
Review
: Smart drugs are among the most common drugs used by students. It is estimated that they are second in incidence after cannabis. Although they are usually used for diseases such as attention deficit hyperactivity disorder (ADHD) and dementia, in most cases the use of smart drugs is illegal and without a prescription. : A systematic review was conducted according to PRISMA guidelines. SCOPUS, Medline (using PubMed as a search engine), Embase, Web of Sciences, and Google Scholar were used as search engines from January 1, 1980 to June 1, 2021 to evaluate the association between smart drugs and neuro-enhancement. A total of 4715 articles were collected. Of these, 295 duplicates were removed. A total of 4380 articles did not meet the inclusion criteria. In conclusion, 48 articles were included in the present systematic review. : Most of the studies were survey studies, 1 was a prospective longitudinal study, 1 was a cross-over study, and 1 was an experimental study in an animal model (rats). The largest group of consumers was school or university students. The most frequent reasons for using smart drugs were: better concentration, neuro enhancement, stress reduction, time optimization, increased wake time, increased free time, and curiosity. There are conflicting opinions, in fact, regarding their actual functioning and benefit, it is not known whether the benefits reported by consumers are due to the drugs, the placebo effect or a combination of these. The real prevalence is underestimated: it is important that the scientific community focus on this issue with further studies on animal models to validate their efficacy.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Cross-Over Studies; Longitudinal Studies; Pharmaceutical Preparations; Prospective Studies; Rats
PubMed: 34455764
DOI: 10.52586/4948 -
Brain and Behavior Feb 2022Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by starvation and malnutrition, a high incidence of coexisting psychiatric conditions, and treatment resistance. The effect of pharmacotherapy has been controversial.
METHOD
A systematic review was conducted for evidence of an effect of olanzapine versus placebo in adults or its effect as adjuvant treatment of AN in adolescents.
RESULTS
A total of seven articles (304 patients with AN) were identified. There were four double-blind, randomized studies examining the effect of olanzapine in the treatment of AN. The mean difference in body mass index (BMI) at the end of treatment between olanzapine and placebo was 0.67 kg/m (95% confidence interval (CI) 0.15-1.18 kg/m ; p = 0.01; I = 0%, p for heterogeneity < 0.79). The olanzapine groups showed a significant increase in BMI of 0.68 kg/m (95% CI 0.22-1.13 kg/m ; p < 0.001; I = 0%, p for heterogeneity = 0.74) compared to the placebo groups. Only two studies examined the effect of olanzapine as adjuvant treatment in adolescents and showed an increase in BMI of 0.66 kg/m (95% CI -0.36 to 1.67 kg/m ; p = 0.21; I = 11%, p for heterogeneity = 0.32).
DISCUSSION
Olanzapine showed efficacy in the treatment of AN with an increased BMI at the end of treatment in adults. The effect of olanzapine as adjuvant treatment in adolescents remains unclear.
Topics: Adolescent; Adult; Anorexia Nervosa; Benzodiazepines; Body Mass Index; Double-Blind Method; Humans; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35020271
DOI: 10.1002/brb3.2498 -
The Cochrane Database of Systematic... Mar 2019Memantine is a moderate affinity uncompetitive antagonist of glutamate NMDA receptors. It is licensed for use in moderate and severe Alzheimer's disease (AD); in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Memantine is a moderate affinity uncompetitive antagonist of glutamate NMDA receptors. It is licensed for use in moderate and severe Alzheimer's disease (AD); in the USA, it is also widely used off-label for mild AD.
OBJECTIVES
To determine efficacy and safety of memantine for people with dementia. To assess whether memantine adds benefit for people already taking cholinesterase inhibitors (ChEIs).
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register of trials (http://www.medicine.ox.ac.uk/alois/) up to 25 March 2018. We examined clinical trials registries, press releases and posters of memantine manufacturers; and the web sites of the FDA, EMEA and NICE. We contacted authors and companies for missing information.
SELECTION CRITERIA
Double-blind, parallel group, placebo-controlled, randomised trials of memantine in people with dementia.
DATA COLLECTION AND ANALYSIS
We pooled and analysed data from four clinical domains across different aetiologies and severities of dementia and for AD with agitation. We assessed the impact of study duration, severity and concomitant use of ChEIs. Consequently, we restricted analyses to the licensed dose (20 mg/day or 28 mg extended release) and data at six to seven months duration of follow-up, and analysed separately results for mild and moderate-to-severe AD.We transformed results for efficacy outcomes into the difference in points on particular outcome scales.
MAIN RESULTS
Across all types of dementia, data were available from almost 10,000 participants in 44 included trials, most of which were at low or unclear risk of bias. For nearly half the studies, relevant data were obtained from unpublished sources. The majority of trials (29 in 7885 participants) were conducted in people with AD.1. Moderate-to-severe AD (with or without concomitant ChEIs). High-certainty evidence from up to 14 studies in around 3700 participants consistently shows a small clinical benefit for memantine versus placebo: clinical global rating (CGR): 0.21 CIBIC+ points (95% confidence interval (CI) 0.14 to 0.30); cognitive function (CF): 3.11 Severe Impairment Battery (SIB) points (95% CI 2.42 to 3.92); performance on activities of daily living (ADL): 1.09 ADL19 points (95% CI 0.62 to 1.64); and behaviour and mood (BM): 1.84 Neuropsychiatric Inventory (NPI) points (95% CI 1.05 to 2.76). There may be no difference in the number of people discontinuing memantine compared to placebo: risk ratio (RR) 0.93 (95% CI 0.83 to 1.04) corresponding to 13 fewer people per 1000 (95% CI 31 fewer to 7 more). Although there is moderate-certainty evidence that fewer people taking memantine experience agitation as an adverse event: RR 0.81 (95% CI 0.66 to 0.99) (25 fewer people per 1000, 95% CI 1 to 44 fewer), there is also moderate-certainty evidence, from three additional studies, suggesting that memantine is not beneficial as a treatment for agitation (e.g. Cohen Mansfield Agitation Inventory: clinical benefit of 0.50 CMAI points, 95% CI -3.71 to 4.71) .The presence of concomitant ChEI does not impact on the difference between memantine and placebo, with the possible exceptions of the BM outcome (larger effect in people taking ChEIs) and the CF outcome (smaller effect).2. Mild AD (Mini Mental State Examination (MMSE) 20 to 23): mainly moderate-certainty evidence based on post-hoc subgroups from up to four studies in around 600 participants suggests there is probably no difference between memantine and placebo for CF: 0.21 ADAS-Cog points (95% CI -0.95 to 1.38); performance on ADL: -0.07 ADL 23 points (95% CI -1.80 to 1.66); and BM: -0.29 NPI points (95% CI -2.16 to 1.58). There is less certainty in the CGR evidence, which also suggests there may be no difference: 0.09 CIBIC+ points (95% CI -0.12 to 0.30). Memantine (compared with placebo) may increase the numbers of people discontinuing treatment because of adverse events (RR 2.12, 95% CI 1.03 to 4.39).3. Mild-to-moderate vascular dementia. Moderate- and low-certainty evidence from two studies in around 750 participants indicates there is probably a small clinical benefit for CF: 2.15 ADAS-Cog points (95% CI 1.05 to 3.25); there may be a small clinical benefit for BM: 0.47 NOSGER disturbing behaviour points (95% CI 0.07 to 0.87); there is probably no difference in CGR: 0.03 CIBIC+ points (95% CI -0.28 to 0.34); and there may be no difference in ADL: 0.11 NOSGER II self-care subscale points (95% CI -0.35 to 0.54) or in the numbers of people discontinuing treatment: RR 1.05 (95% CI 0.83 to 1.34).There is limited, mainly low- or very low-certainty efficacy evidence for other types of dementia (Parkinson's disease and dementia Lewy bodies (for which CGR may show a small clinical benefit; four studies in 319 people); frontotemporal dementia (two studies in 133 people); and AIDS-related Dementia Complex (one study in 140 people)).There is high-certainty evidence showing no difference between memantine and placebo in the proportion experiencing at least one adverse event: RR 1.03 (95% CI 1.00 to 1.06); the RR does not differ between aetiologies or severities of dementia. Combining available data from all trials, there is moderate-certainty evidence that memantine is 1.6 times more likely than placebo to result in dizziness (6.1% versus 3.9%), low-certainty evidence of a 1.3-fold increased risk of headache (5.5% versus 4.3%), but high-certainty evidence of no difference in falls.
AUTHORS' CONCLUSIONS
We found important differences in the efficacy of memantine in mild AD compared to that in moderate-to-severe AD. There is a small clinical benefit of memantine in people with moderate-to-severe AD, which occurs irrespective of whether they are also taking a ChEI, but no benefit in people with mild AD.Clinical heterogeneity in AD makes it unlikely that any single drug will have a large effect size, and means that the optimal drug treatment may involve multiple drugs, each having an effect size that may be less than the minimum clinically important difference.A definitive long-duration trial in mild AD is needed to establish whether starting memantine earlier would be beneficial over the long term and safe: at present the evidence is against this, despite it being common practice. A long-duration trial in moderate-to-severe AD is needed to establish whether the benefit persists beyond six months.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Akathisia, Drug-Induced; Alzheimer Disease; Cognition Disorders; Dementia; Dementia, Vascular; Excitatory Amino Acid Antagonists; Humans; Memantine; Randomized Controlled Trials as Topic; Withholding Treatment
PubMed: 30891742
DOI: 10.1002/14651858.CD003154.pub6 -
Hormone and Metabolic Research =... Jul 2022Aim To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in... (Meta-Analysis)
Meta-Analysis
Aim To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in overweight/obese patients without diabetes. The random-effect model was used to pool data extracted from included literatures. The weighted mean difference (WMD), odds ratio and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD 42020173199). The sources of intertrial heterogeneity, bias and the robustness of results were evaluated by subgroup analysis, sensitivity analysis and regression analysis, respectively. A total of 24 RCTs were recruited in the present analysis which included 5867 patients. The results showed that the treatment of overweight/obese patients without diabetes with GLP-1RAs including liraglutide, exenatide and semaglutide significantly achieved greater weight loss than placebo [WMD=-5.39, 95% CI (-6.82, -3.96)] and metformin [WMD=-5.46, 95% CI (-5.87, -5.05)]. The subgroup analysis showed that semaglutide displayed the most obvious antiobesity effect in terms of weight loss, the reduction of body mass index (BMI) and waist circumference (WC). However, GLP-1RAs treatments had more gastrointestinal adverse events (such as nausea and vomiting) than placebo and Met. The subgroup analysis also represented that semaglutide displayed the lowest risk of gastrointestinal adverse events among three kinds of GLP-1RAs. Our meta-analysis demonstrated that GLP-1RA had a superior antiobesity effect than placebo/Met in overweight/obese patients without diabetes in terms of body weight, BMI, and WC, especially for semaglutide, which had more obvious antiobesity effect and lower GI adverse events than liraglutide and exenatide.
Topics: Anti-Obesity Agents; Exenatide; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Liraglutide; Obesity; Weight Loss
PubMed: 35512849
DOI: 10.1055/a-1844-1176