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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 -
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 -
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 -
Phytotherapy Research : PTR Mar 2018A systematic review and network-meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus... (Review)
Review
A systematic review and network-meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus other comparators (i.e., placebo/control/other galactagogues). A pairwise comparison for the treatment effect was carried out to generate the forest plot for the NMA. League tables were generated using treatment effect, weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise comparisons, where WMD > 0 favors the column-defining treatment. Five studies were identified with 122 participants receiving treatment with fenugreek. The NMA results of 4 studies indicated that consumption of fenugreek significantly increased amount of the produced breast milk [11.11, CI 95% 6.77, 15.46] versus placebo. The pairwise comparison revealed that fenugreek was effective as a galactagogue compared to placebo, control, and reference groups WMD 17.79 [CI 11.71, 23.88]. However, the effect of fenugreek was substantially inferior to Coleus amboinicus Lour and palm date. The NMA using pairwise comparison demonstrated the effect of C. amboinicus and palm date in the stimulation of the breast milk production was comparable and superior to all comparators.
Topics: Female; Galactogogues; Humans; Network Meta-Analysis; Plant Extracts; Trigonella
PubMed: 29193352
DOI: 10.1002/ptr.5972 -
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 -
The Journal of Orthopaedic and Sports... Jun 2024We aimed to quantify the proportion not attributable to the specific effects (PCE) of physical therapy interventions for musculoskeletal pain. Intervention systematic... (Meta-Analysis)
Meta-Analysis Review
Which Portion of Physiotherapy Treatments' Effect Is Not Attributable to the Specific Effects in People With Musculoskeletal Pain? A Meta-Analysis of Randomized Placebo-Controlled Trials.
We aimed to quantify the proportion not attributable to the specific effects (PCE) of physical therapy interventions for musculoskeletal pain. Intervention systematic review with meta-analysis. We searched Ovid, MEDLINE, EMBASE, CINAHL, Scopus, PEDro, Cochrane Controlled Trials Registry, and SPORTDiscus databases from inception to April 2023. Randomized placebo-controlled trials evaluating the effect of physical therapy interventions on musculoskeletal pain. Risk of bias was evaluated using the Cochrane risk-of-bias tool for randomized trials (RoB 2). The proportion of physical therapy interventions effect that was not explained by the specific effect of the intervention was calculated, using the proportion not attributable to the specific effects (PCE) metric, and a quantitative summary of the data from the studies was conducted using the random-effects inverse-variance model (Hartung-Knapp-Sidik-Jonkman method). Sixty-eight studies were included in the systematic review (participants: n = 5238), and 54 placebo-controlled trials informed our meta-analysis (participants: n = 3793). Physical therapy interventions included soft tissue techniques, mobilization, manipulation, taping, exercise therapy, and dry needling. Placebo interventions included manual, nonmanual interventions, or both. The proportion not attributable to the specific effects of mobilization accounted for 88% of the immediate overall treatment effect for pain intensity (PCE = 0.88, 95% confidence interval [CI]: 0.57, 1.20). In exercise therapy, this proportion accounted for 46% of the overall treatment effect for pain intensity (PCE = 0.46, 95% CI: 0.41, 0.52). The PCE in manipulation excelled in short-term pain relief (PCE = 0.81, 95% CI: 0.62, 1.01) and in mobilization in long-term effects (PCE = 0.86, 95% CI: 0.76, 0.96). In taping, the PCE accounted for 64% of disability improvement (PCE = 0.64, 95% CI: 0.48, 0.80). The outcomes of physical therapy interventions for musculoskeletal pain were significantly influenced by factors not attributable to the specific effects of the interventions. Boosting these factors consciously to enhance therapeutic outcomes represents an ethical opportunity that could benefit patients. .
Topics: Humans; Musculoskeletal Pain; Randomized Controlled Trials as Topic; Physical Therapy Modalities; Exercise Therapy
PubMed: 38602164
DOI: 10.2519/jospt.2024.12126 -
The Cochrane Database of Systematic... May 2022Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead... (Review)
Review
BACKGROUND
Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti-spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required.
OBJECTIVES
To assess benefit and harms of cannabinoids, including synthetic, or herbal and plant-derived cannabinoids, for reducing symptoms for adults with MS.
SEARCH METHODS
We searched the following databases from inception to December 2021: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), CINAHL (EBSCO host), LILACS, the Physiotherapy Evidence Database (PEDro), the World Health Organisation International Clinical Trials Registry Platform, the US National Institutes of Health clinical trial register, the European Union Clinical Trials Register, the International Association for Cannabinoid Medicines databank. We hand searched citation lists of included studies and relevant reviews.
SELECTION CRITERIA
We included randomised parallel or cross-over trials (RCTs) evaluating any cannabinoid (including herbal Cannabis, Cannabis flowers, plant-based cannabinoids, or synthetic cannabinoids) irrespective of dose, route, frequency, or duration of use for adults with MS.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane Risk of bias 2 tool for parallel RCTs and crossover trials. We rated the certainty of evidence using the GRADE approach for the following outcomes: reduction of 30% in the spasticity Numeric Rating Scale, pain relief of 50% or greater in the Numeric Rating Scale-Pain Intensity, much or very much improvement in the Patient Global Impression of Change (PGIC), Health-Related Quality of Life (HRQoL), withdrawals due to adverse events (AEs) (tolerability), serious adverse events (SAEs), nervous system disorders, psychiatric disorders, physical dependence.
MAIN RESULTS
We included 25 RCTs with 3763 participants of whom 2290 received cannabinoids. Age ranged from 18 to 60 years, and between 50% and 88% participants across the studies were female. The included studies were 3 to 48 weeks long and compared nabiximols, an oromucosal spray with a plant derived equal (1:1) combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (13 studies), synthetic cannabinoids mimicking THC (7 studies), an oral THC extract of Cannabis sativa (2 studies), inhaled herbal Cannabis (1 study) against placebo. One study compared dronabinol, THC extract of Cannabis sativa and placebo, one compared inhaled herbal Cannabis, dronabinol and placebo. We identified eight ongoing studies. Critical outcomes • Spasticity: nabiximols probably increases the number of people who report an important reduction of perceived severity of spasticity compared with placebo (odds ratio (OR) 2.51, 95% confidence interval (CI) 1.56 to 4.04; 5 RCTs, 1143 participants; I = 67%; moderate-certainty evidence). The absolute effect was 216 more people (95% CI 99 more to 332 more) per 1000 reporting benefit with cannabinoids than with placebo. • Chronic neuropathic pain: we found only one small trial that measured the number of participants reporting substantial pain relief with a synthetic cannabinoid compared with placebo (OR 4.23, 95% CI 1.11 to 16.17; 1 study, 48 participants; very low-certainty evidence). We are uncertain whether cannabinoids reduce chronic neuropathic pain intensity. • Treatment discontinuation due to AEs: cannabinoids may increase slightly the number of participants who discontinue treatment compared with placebo (OR 2.41, 95% CI 1.51 to 3.84; 21 studies, 3110 participants; I² = 17%; low-certainty evidence); the absolute effect is 39 more people (95% CI 15 more to 76 more) per 1000 people. Important outcomes • PGIC: cannabinoids probably increase the number of people who report 'very much' or 'much' improvement in health status compared with placebo (OR 1.80, 95% CI 1.37 to 2.36; 8 studies, 1215 participants; I² = 0%; moderate-certainty evidence). The absolute effect is 113 more people (95% CI 57 more to 175 more) per 1000 people reporting improvement. • HRQoL: cannabinoids may have little to no effect on HRQoL (SMD -0.08, 95% CI -0.17 to 0.02; 8 studies, 1942 participants; I = 0%; low-certainty evidence); • SAEs: cannabinoids may result in little to no difference in the number of participants who have SAEs compared with placebo (OR 1.38, 95% CI 0.96 to 1.99; 20 studies, 3124 participants; I² = 0%; low-certainty evidence); • AEs of the nervous system: cannabinoids may increase nervous system disorders compared with placebo (OR 2.61, 95% CI 1.53 to 4.44; 7 studies, 1154 participants; I² = 63%; low-certainty evidence); • Psychiatric disorders: cannabinoids may increase psychiatric disorders compared with placebo (OR 1.94, 95% CI 1.31 to 2.88; 6 studies, 1122 participants; I² = 0%; low-certainty evidence); • Drug tolerance: the evidence is very uncertain about the effect of cannabinoids on drug tolerance (OR 3.07, 95% CI 0.12 to 75.95; 2 studies, 458 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Compared with placebo, nabiximols probably reduces the severity of spasticity in the short-term in people with MS. We are uncertain about the effect on chronic neurological pain and health-related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo. We are uncertain about the effect on drug tolerance. The overall certainty of evidence is limited by short-term duration of the included studies.
Topics: Activities of Daily Living; Adolescent; Adult; Analgesics; Cannabinoids; Cannabis; Chronic Pain; Dronabinol; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Plant Extracts; Quality of Life; Young Adult
PubMed: 35510826
DOI: 10.1002/14651858.CD013444.pub2 -
Anesthesiology Aug 2021Chronic postsurgical pain can severely impair patient health and quality of life. This systematic review update evaluated the effectiveness of systemic drugs to prevent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic postsurgical pain can severely impair patient health and quality of life. This systematic review update evaluated the effectiveness of systemic drugs to prevent chronic postsurgical pain.
METHODS
The authors included double-blind, placebo-controlled, randomized controlled trials including adults that evaluated perioperative systemic drugs. Studies that evaluated same drug(s) administered similarly were pooled. The primary outcome was the proportion reporting any pain at 3 or more months postsurgery.
RESULTS
The authors identified 70 new studies and 40 from 2013. Most evaluated ketamine, pregabalin, gabapentin, IV lidocaine, nonsteroidal anti-inflammatory drugs, and corticosteroids. Some meta-analyses showed statistically significant-but of unclear clinical relevance-reductions in chronic postsurgical pain prevalence after treatment with pregabalin, IV lidocaine, and nonsteroidal anti-inflammatory drugs. Meta-analyses with more than three studies and more than 500 participants showed no effect of ketamine on prevalence of any pain at 6 months when administered for 24 h or less (risk ratio, 0.62 [95% CI, 0.36 to 1.07]; prevalence, 0 to 88% ketamine; 0 to 94% placebo) or more than 24 h (risk ratio, 0.91 [95% CI, 0.74 to 1.12]; 6 to 71% ketamine; 5 to 78% placebo), no effect of pregabalin on prevalence of any pain at 3 months (risk ratio, 0.88 [95% CI, 0.70 to 1.10]; 4 to 88% pregabalin; 3 to 80% placebo) or 6 months (risk ratio, 0.78 [95% CI, 0.47 to 1.28]; 6 to 68% pregabalin; 4 to 69% placebo) when administered more than 24 h, and an effect of pregabalin on prevalence of moderate/severe pain at 3 months when administered more than 24 h (risk ratio, 0.47 [95% CI, 0.33 to 0.68]; 0 to 20% pregabalin; 4 to 34% placebo). However, the results should be interpreted with caution given small study sizes, variable surgical types, dosages, timing and method of outcome measurements in relation to the acute pain trajectory in question, and preoperative pain status.
CONCLUSIONS
Despite agreement that chronic postsurgical pain is an important topic, extremely little progress has been made since 2013, likely due to study designs being insufficient to address the complexities of this multifactorial problem.
Topics: Adrenal Cortex Hormones; Adult; Analgesics; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Humans; Pain, Postoperative
PubMed: 34237128
DOI: 10.1097/ALN.0000000000003837 -
The American Journal of Psychiatry Oct 2017Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences.
METHOD
The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression.
RESULTS
The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time.
CONCLUSIONS
Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.
Topics: Antipsychotic Agents; Bayes Theorem; Depression; Drug-Related Side Effects and Adverse Reactions; Humans; Multivariate Analysis; Patient Dropouts; Psychotic Disorders; Quality of Life; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Treatment Outcome
PubMed: 28541090
DOI: 10.1176/appi.ajp.2017.16121358 -
The Cochrane Database of Systematic... Jun 2018Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Guidelines suggest limited and cautious use of antipsychotics for treatment of delirium where nonpharmacological interventions have failed and symptoms remain distressing or dangerous, or both. It is unclear how well these recommendations are supported by current evidence.
OBJECTIVES
Our primary objective was to assess the efficacy of antipsychotics versus nonantipsychotics or placebo on the duration of delirium in hospitalised adults. Our secondary objectives were to compare the efficacy of: 1) antipsychotics versus nonantipsychotics or placebo on delirium severity and resolution, mortality, hospital length of stay, discharge disposition, health-related quality of life, and adverse effects; and 2) atypical vs. typical antipsychotics for reducing delirium duration, severity, and resolution, hospital mortality and length of stay, discharge disposition, health-related quality of life, and adverse effects.
SEARCH METHODS
We searched MEDLINE, Embase, Cochrane EBM Reviews, CINAHL, Thomson Reuters Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) from their respective inception dates until July 2017. We also searched the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database, Web of Science ISI Proceedings, and other grey literature.
SELECTION CRITERIA
We included randomised and quasi-randomised trials comparing 1) antipsychotics to nonantipsychotics or placebo and 2) typical to atypical antipsychotics for the treatment of delirium in adult hospitalised (but not critically ill) patients.
DATA COLLECTION AND ANALYSIS
We examined titles and abstracts of identified studies to determine eligibility. We extracted data independently in duplicate. Disagreements were settled by further discussion and consensus. We used risk ratios (RR) with 95% confidence intervals (CI) as a measure of treatment effect for dichotomous outcomes, and between-group standardised mean differences (SMD) with 95% CI for continuous outcomes.
MAIN RESULTS
We included nine trials that recruited 727 participants. Four of the nine trials included a comparison of an antipsychotic to a nonantipsychotic drug or placebo and seven included a comparison of a typical to an atypical antipsychotic. The study populations included hospitalised medical, surgical, and palliative patients.No trial reported on duration of delirium. Antipsychotic treatment did not reduce delirium severity compared to nonantipsychotic drugs (standard mean difference (SMD) -1.08, 95% CI -2.55 to 0.39; four studies; 494 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (SMD -0.17, 95% CI -0.37 to 0.02; seven studies; 542 participants; low-quality evidence). There was no evidence antipsychotics resolved delirium symptoms compared to nonantipsychotic drug regimens (RR 0.95, 95% CI 0.30 to 2.98; three studies; 247 participants; very low-quality evidence); nor was there a difference between typical and atypical antipsychotics (RR 1.10, 95% CI 0.79 to 1.52; five studies; 349 participants; low-quality evidence). The pooled results indicated that antipsychotics did not alter mortality compared to nonantipsychotic regimens (RR 1.29, 95% CI 0.73 to 2.27; three studies; 319 participants; low-quality evidence) nor was there a difference between typical and atypical antipsychotics (RR 1.71, 95% CI 0.82 to 3.35; four studies; 342 participants; low-quality evidence).No trial reported on hospital length of stay, hospital discharge disposition, or health-related quality of life. Adverse event reporting was limited and measured with inconsistent methods; in those reporting events, the number of events were low. No trial reported on physical restraint use, long-term cognitive outcomes, cerebrovascular events, or QTc prolongation (i.e. increased time in the heart's electrical cycle). Only one trial reported on arrhythmias and seizures, with no difference between typical or atypical antipsychotics. We found antipsychotics did not have a higher risk of extrapyramidal symptoms (EPS) compared to nonantipsychotic drugs (RR 1.70, 95% CI 0.04 to 65.57; three studies; 247 participants; very-low quality evidence); pooled results showed no increased risk of EPS with typical antipsychotics compared to atypical antipsychotics (RR 12.16, 95% CI 0.55 to 269.52; two studies; 198 participants; very low-quality evidence).
AUTHORS' CONCLUSIONS
There were no reported data to determine whether antipsychotics altered the duration of delirium, length of hospital stay, discharge disposition, or health-related quality of life as studies did not report on these outcomes. From the poor quality data available, we found antipsychotics did not reduce delirium severity, resolve symptoms, or alter mortality. Adverse effects were poorly or rarely reported in the trials. Extrapyramidal symptoms were not more frequent with antipsychotics compared to nonantipsychotic drug regimens, and no different for typical compared to atypical antipsychotics.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Female; Haloperidol; Hospitalization; Humans; Male; Olanzapine; Placebo Effect; Randomized Controlled Trials as Topic; Risperidone
PubMed: 29920656
DOI: 10.1002/14651858.CD005594.pub3