-
BMC Pharmacology & Toxicology Apr 2023Standard doses of second-generation H-antihistamines (sgAHs) as first-line treatment are not always effective in treating chronic spontaneous urticaria (CSU), and hence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Standard doses of second-generation H-antihistamines (sgAHs) as first-line treatment are not always effective in treating chronic spontaneous urticaria (CSU), and hence an increase in the dose of sgAHs is recommended. However, literature evaluating the efficacy and safety of this treatment remains inconclusive, highlighting the need for a systematic review and meta-analysis. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of high-dose sgAHs compared with standard-dose sgAHs in treating CSU.
METHODS
A systematic literature search of double-blind, randomized controlled trials (RCT) utilizing multiple doses of sgAHs was performed by searching the electronic databases Medline, Embase, PsycInfo, Cochrane databases, and Web of Science. Bibliographies were also manually searched. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The response rate, the number of adverse events, somnolence, and withdrawal due to adverse events were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. RevMan (V5.3) software was used for data synthesis.
RESULTS
A total of 13 studies were identified, seven of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that high-dose sgAHs was associated with a significantly higher response rate than standard-dose (RR 1.13, 95% CI 1.02 to 1.26; P = 0.02). Conversely, high doses of sgAHs were associated with significantly higher somnolence rates than standard dose (RD 0.05, 95% CI 0.01 to 0.09; P = 0.02). There was no significant difference in adverse events or withdrawal due to adverse events between standard- and high-dose treatments.
CONCLUSIONS
Our analyses showed that a high dose of sgAHs (up to two times the standard dose) might be more effective than a standard dose in CSU treatment. High-dose and standard-dose sgAHs showed similar adverse events, except for somnolence, where incidence was found to be dose-dependent in some studies. However, given the limited number of studies, our meta-analysis results should be interpreted with caution.
Topics: Humans; Sleepiness; Randomized Controlled Trials as Topic; Chronic Urticaria; Histamine H1 Antagonists, Non-Sedating; Histamine Antagonists
PubMed: 37024900
DOI: 10.1186/s40360-023-00665-y -
Pharmaceuticals (Basel, Switzerland) Jan 2022Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically... (Review)
Review
Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64-31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92-152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33-68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19-9.78), dizziness (OR: 4.60 95% CI: 2.39-8.83) and headache (OR: 2.90; 95% CI: 1.07-7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.
PubMed: 35056154
DOI: 10.3390/ph15010100 -
The Cochrane Database of Systematic... Oct 2019Fluoxetine is a serotonin reuptake inhibitor indicated for major depression. It is also thought to affect weight control: this seems to happen through appetite changes... (Review)
Review
BACKGROUND
Fluoxetine is a serotonin reuptake inhibitor indicated for major depression. It is also thought to affect weight control: this seems to happen through appetite changes resulting in decreased food intake and normalisation of unusual eating behaviours. However, the benefit-risk ratio of this off-label medication is unclear.
OBJECTIVES
To assess the effects of fluoxetine for overweight or obese adults.
SEARCH METHODS
We searched the Cochrane Library, MEDLINE, Embase, LILACS, the ICTRP Search Portal and ClinicalTrials.gov and World Health Organization (WHO) ICTRP Search Portal. The last date of the search was December 2018 for all databases, to which we applied no language restrictions .
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the administration of fluoxetine versus placebo, other anti-obesity agents, non-pharmacological therapy or no treatment in overweight or obese adults without depression, mental illness or abnormal eating patterns.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened abstracts and titles for relevance. Screening for inclusion, data extraction and risk of bias assessment was performed by one author and checked by the second. We assessed trials for the overall certainty of the evidence using the GRADE instrument. For additional information we contacted trial authors by email. We performed random-effects meta-analyses and calculated the risk ratio (RR) with 95% confidence intervals (95% CI) for dichotomous outcomes and the mean difference (MD) with 95% CI for continuous outcomes.
MAIN RESULTS
We identified 1036 records, scrutinized 52 full-text articles and included 19 completed RCTs (one trial is awaiting assessment). A total of 2216 participants entered the trials, 1280 participants were randomly assigned to fluoxetine (60 mg/d, 40 mg/d, 20 mg/d and 10 mg/d) and 936 participants were randomly assigned to various comparison groups (placebo; the anti-obesity agents diethylpropion, fenproporex, mazindol, sibutramine, metformin, fenfluramine, dexfenfluramine, fluvoxamine, 5-hydroxy-tryptophan; no treatment; and omega-3 gel). Within the 19 RCTs there were 56 trial arms. Fifteen trials were parallel RCTs and four were cross-over RCTs. The participants in the included trials were followed up for periods between three weeks and one year. The certainty of the evidence was low or very low: the majority of trials had a high risk of bias in one or more of the risk of bias domains.For our main comparison group - fluoxetine versus placebo - and across all fluoxetine dosages and durations of treatment, the MD was -2.7 kg (95% CI -4 to -1.4; P < 0.001; 10 trials, 956 participants; low-certainty evidence). The 95% prediction interval ranged between -7.1 kg and 1.7 kg. The MD in body mass index (BMI) reduction across all fluoxetine dosages compared with placebo was -1.1 kg/m² (95% CI -3.7 to 1.4; 3 trials, 97 participants; very low certainty evidence). Only nine placebo-controlled trials reported adverse events. A total of 399 out of 627 participants (63.6%) receiving fluoxetine compared with 352 out of 626 participants (56.2%) receiving placebo experienced an adverse event. Random-effects meta-analysis showed an increase in the risk of having at least one adverse event of any type in the fluoxetine groups compared with placebo (RR 1.18, 95% CI 0.99 to 1.42; P = 0.07; 9 trials, 1253 participants; low-certainty evidence). The 95% prediction interval ranged between 0.74 and 1.88. Following fluoxetine treatment the adverse events of dizziness, drowsiness, fatigue, insomnia and nausea were observed approximately twice as often compared to placebo. A total of 15 out of 197 participants (7.6%) receiving fluoxetine compared with 12 out of 196 participants (6.1%) receiving placebo experienced depression. The RR across all fluoxetine doses compared with placebo was 1.20 (95% CI 0.57 to 2.52; P = 0.62; 3 trials, 393 participants; very low certainty evidence). All-cause mortality, health-related quality of life and socioeconomic effects were not reported.The comparisons of fluoxetine with other anti-obesity agents (3 trials, 234 participants), omega-3 gel (1 trial, 48 participants) and no treatment (1 trial, 60 participants) showed inconclusive results (very low certainty evidence).
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests that off-label fluoxetine may decrease weight compared with placebo. However, low-certainty evidence suggests an increase in the risk for dizziness, drowsiness, fatigue, insomnia and nausea following fluoxetine treatment.
PubMed: 31613390
DOI: 10.1002/14651858.CD011688.pub2 -
European Archives of... Oct 2023Hypoglossal nerve stimulation (HNS) has recently been introduced as an alternative treatment for patients with OSA. A large number of studies have demonstrated... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Hypoglossal nerve stimulation (HNS) has recently been introduced as an alternative treatment for patients with OSA. A large number of studies have demonstrated substantial changes in OSA with this therapy by reducing respiratory events and improving symptoms such as daytime sleepiness and quality of life. The objective of this review was to conduct a systematic review and meta-analysis to evaluate patient-reported outcomes and experience with HNS therapy.
METHODS
A systematic literature search of MEDLINE, Cochrane, and Web of Science was performed to identify randomized controlled and observational studies reporting subjective outcomes with different HNS systems in patients with OSA. Abstracts of 406 articles were screened and a subset of 55 articles were reviewed for eligibility. Risk of bias was assessed using the ROBINS-I tool. Meta-analysis using RevMan was performed when > 2 studies were identified that reported data on a specific outcome.
RESULTS
Thirty-four publications reporting data on 3785 patients with a mean follow-up of 11.8 ± 12.2 months were identified and included in the meta-analysis. The analysis revealed a pooled effect of 4.59 points improvement in daytime sleepiness as measured by the ESS questionnaire (Z = 42.82, p < .001), 2.84 points improvement in daytime functioning as measured by the FOSQ score (Z = 28.38, p < .001), and 1.77 points improvement in sleep quality as measured by the PSQI questionnaire (Z = 2.53, p = .010). Patient-reported experience was consistently positive and revealed additional relevant aspects from this perspective.
CONCLUSION
HNS therapy significantly improves quality of life in patients with OSA and reliably produces clinically meaningful effects on daytime sleepiness, daytime functioning, and sleep quality. Treatment regularly meets or exceeds the minimum clinically important differences defined for the respective instruments. Additional research is needed to further investigate effects on quality of life beyond improvements in daytime sleepiness and daytime functioning.
Topics: Humans; Hypoglossal Nerve; Sleep Apnea, Obstructive; Patient Reported Outcome Measures; Quality of Life; Electric Stimulation Therapy
PubMed: 37354340
DOI: 10.1007/s00405-023-08062-1 -
BMJ (Clinical Research Ed.) Oct 2010To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and relative adverse effects of tricyclic antidepressants in the treatment of migraine, tension-type, and mixed headaches.
DESIGN
Meta-analysis.
DATA SOURCES
Medline, Embase, the Cochrane Trials Registry, and PsycLIT. Studies reviewed Randomised trials of adults receiving tricyclics as only treatment for a minimum of four weeks.
DATA EXTRACTION
Frequency of headaches (number of headache attacks for migraine and number of days with headache for tension-type headaches), intensity of headache, and headache index.
RESULTS
37 studies met the inclusion criteria. Tricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference -1.29, 95% confidence interval -2.18 to -0.39 and -0.70, -0.93 to -0.48) but not compared with selective serotonin reuptake inhibitors (-0.80, -2.63 to 0.02 and -0.20, -0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (β=-0.11, 95% confidence interval -0.63 to -0.15; P<0.0005). Tricyclics were also more likely to reduce the intensity of headaches by at least 50% than either placebo (tension-type: relative risk 1.41, 95% confidence interval 1.02 to 1.89; migraine: 1.80, 1.24 to 2.62) or selective serotonin reuptake inhibitors (1.73, 1.34 to 2.22 and 1.72, 1.15 to 2.55). Tricyclics were more likely to cause adverse effects than placebo (1.53, 95% confidence interval 1.11 to 2.12) and selective serotonin reuptake inhibitors (2.22, 1.52 to 3.32), including dry mouth (P<0.0005 for both), drowsiness (P<0.0005 for both), and weight gain (P<0.001 for both), but did not increase dropout rates (placebo: 1.22, 0.83 to 1.80, selective serotonin reuptake inhibitors: 1.16, 0.81 to 2.97).
CONCLUSIONS
Tricyclic antidepressants are effective in preventing migraine and tension-type headaches and are more effective than selective serotonin reuptake inhibitors, although with greater adverse effects. The effectiveness of tricyclics seems to increase over time.
Topics: Adult; Antidepressive Agents, Tricyclic; Headache Disorders; Humans; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome
PubMed: 20961988
DOI: 10.1136/bmj.c5222 -
Clocks & Sleep May 2022The objectives of this empirical study are to describe and discuss the current literature available on the relationship between excessive daytime sleepiness (EDS) and... (Review)
Review
The objectives of this empirical study are to describe and discuss the current literature available on the relationship between excessive daytime sleepiness (EDS) and the socioeconomic position (SEP) as well as to provide recommendations for consideration of SEP in sleep medicine and biomedical research. Databases Medline/PubMed, Web of Science, Google scholar and Scopus were screened from January 1990 to December 2020 using PRISMA guidelines and 20 articles were included in the final synthesis. Nineteen studies were cross-sectional and one study was longitudinal. Among these studies, 25.00% (n = 5) are focused on children and adolescent and the remaining 75.00% (n = 15) focused on adults and seniors. Ages ranged from 8 to 18 years old for children/adolescent and ranged from 18 to 102 years old for adults. Main SEP measures presented in these studies were education, income, perceived socioeconomic status and employment. The sample size in these studies varied from N = 90 participants to N = 33,865 participants. Overall, a lower educational level, a lower income and full-time employment were associated with EDS. Symptoms of EDS are prevalent in women, especially those with a low income or no job; and children and adolescents with difficult living conditions or working part time reported more sleep disturbances. SEP is already considered as an important determinant for many health outcomes, but if SEP is embedded in the experimental design in psychosomatic research, biomedical research and clinical practice as a constant variable regardless of outcome; it will move forward future investigations.
PubMed: 35645243
DOI: 10.3390/clockssleep4020022 -
Pharmacological Research Dec 2022Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in... (Review)
Review
Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.
Topics: Adult; Humans; Fibromyalgia; Antidepressive Agents; Fatigue; Musculoskeletal Pain; Employment
PubMed: 36336218
DOI: 10.1016/j.phrs.2022.106547 -
International Journal of Environmental... Feb 2023Airline cabin crew operate in dynamic work environments that are continuously changing, from unpredictable shift work hours to travelling through multiple time zones.... (Review)
Review
Airline cabin crew operate in dynamic work environments that are continuously changing, from unpredictable shift work hours to travelling through multiple time zones. These likely impact cabin crews' overall health and may affect their performance on safety-related tasks. Research on this population has been limited; therefore, the aim was to summarise the relevant literature regarding fatigue, sleepiness and mental health of cabin crew. This review followed the PRISMA-ScR guidelines and conducted a systematic search utilising five databases. The initial search identified 1223 studies, and through vigorous screening processes, 27 studies were selected for this review. Over half of the selected studies focused on international or long-haul flights, and a large proportion of the sample participants were women. Findings suggested a high prevalence of fatigue and sleepiness as well as unsatisfactory sleep quality with elevated susceptibility to sleep disorders. Factors identified with health outcomes were associated with flight operations (e.g., rosters) and individual differences (e.g., age and coping strategies). Regarding mental health, cabin crews are potentially at a greater risk for depression and anxiety compared to the general public. This review draws attention to the importance of using a standardised approach, such as validated measures for fair and consistent inferences.
Topics: Humans; Female; Male; Sleepiness; Sleep; Wakefulness; Fatigue
PubMed: 36768014
DOI: 10.3390/ijerph20032652 -
The Cochrane Database of Systematic... Oct 2019Epilepsy affects approximately 1% of the population, with up to 30% of patients continuing to have seizures, despite antiepileptic drug treatment. Clobazam is a... (Review)
Review
BACKGROUND
Epilepsy affects approximately 1% of the population, with up to 30% of patients continuing to have seizures, despite antiepileptic drug treatment. Clobazam is a 1,5-benzodiazepine and is commonly used as an add-on treatment for drug-resistant epilepsy. This review is an updated version of the original Cochrane Review, first published in 2008, and examines the most current literature regarding clobazam as an add-on for drug-resistant epilepsy.
OBJECTIVES
To assess the efficacy, effectiveness and tolerability of clobazam as an add-on therapy for drug-resistant generalised-onset and focal-onset seizures, with or without secondary generalisation, in adults and children.
SEARCH METHODS
For the latest update, we searched the following databases on 9 October 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid) 1946 to 8 October, 2018, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). For some previous updates we also searched SCOPUS, DARE, and BIOSIS Previews, but these are no longer needed. (SCOPUS was searched as a substitute for EMBASE, but randomised and quasi-randomised controlled trials in EMBASE are now included in CENTRAL; DARE ceased operation at the end of March 2015; BIOSIS Previews yielded no relevant items that were not found in the other databases).
SELECTION CRITERIA
Randomised trials of add-on clobazam, with adequate methods of allocation concealment, recruiting patients with drug-resistant focal or generalised-onset seizures, with a minimum treatment period of eight weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: 50% or greater reduction in seizures, seizure freedom, treatment withdrawal and adverse events.
MAIN RESULTS
Four double-blind, placebo-controlled, cross-over studies, representing 197 participants, were included in the review. All four studies were assessed as having unclear risk of bias due to the unavailability of methodological details. The studies demonstrated significant methodological heterogeneity and differences in outcome measures were noted. Consequently, it was not possible to summarise the data in a meta-analysis. Instead, findings were summarised in a narrative data synthesis, Only two of the studies reported 50% or greater seizure reduction. They respectively reported that 57.7% and 52.4% of participants receiving add-on clobazam experienced a 50% or greater reduction in seizure frequency, although publication bias needs to be considered (2 RCTs, n = 47, very low-quality evidence). Seizure freedom was reported by three of the included studies. Collectively, 27 out of 175 patients were seizure-free during treatment with clobazam (3 RCTs, n = 175, very low-quality evidence). Two studies specifically stated that seizure freedom was not observed in any of the participants receiving add-on placebo. Treatment withdrawal was reported by all four studies. There was a slightly higher incidence of treatment withdrawal associated with receiving clobazam, although the overall incidence was still fairly low (4 RCTs, n = 197, very low-quality evidence). Adverse events were only described in two of the studies, reportedly 36% and 85% of participants experienced one or more adverse events whilst receiving clobazam. The most commonly reported adverse event was drowsiness.
AUTHORS' CONCLUSIONS
Clobazam as an add-on treatment may reduce seizure frequency and may be most effective in focal-onset seizures. It is important to recognise that this finding has been derived from very low-quality evidence and from studies judged to have an unclear risk of bias. It remains unclear which population demographic will best benefit from clobazam and over what time-frame. A large-scale, randomised controlled trial, conducted over a greater period of time, incorporating subgroups with differing seizure types, is required to effectively inform clinical practice.
PubMed: 31638272
DOI: 10.1002/14651858.CD004154.pub5 -
PloS One 2015We performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials evaluating suvorexant for primary insomnia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials evaluating suvorexant for primary insomnia.
METHODS
Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations through June 27, 2015. We performed a systematic review and meta-analysis of suvorexant trial efficacy and safety outcomes. The primary efficacy outcomes were either subjective total sleep time (sTST) or subjective time-to-sleep onset (sTSO) at 1 month. The secondary outcomes were other efficacy outcomes, discontinuation rate, and individual adverse events. The risk ratio, number-needed-to-treat/harm, and weighted mean difference (WMD) and 95% confidence intervals (CI) based on a random effects model were calculated.
RESULTS
The computerized literature database search initially yielded 48 results, from which 37 articles were excluded following a review of titles and abstracts and another eight review articles after full-text review. Thus, we identified 4 trials that included a total of 3,076 patients. Suvorexant was superior to placebo with regard to the two primary efficacy outcomes (sTST: WMD = -20.16, 95% CI = -25.01 to -15.30, 1889 patients, 3 trials, sTSO: WMD = -7.62, 95% CI = -11.03 to -4.21, 1889 patients, 3 trials) and was not different from placebo in trial discontinuations. Suvorexant caused a higher incidence than placebo of at least one side effects, abnormal dreams, somnolence, excessive daytime sleepiness/sedation, fatigue, dry mouth, and rebound insomnia.
CONCLUSIONS
Our analysis of published trial results suggests that suvorexant is effective in treating primary insomnia and is well-tolerated.
Topics: Azepines; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Triazoles
PubMed: 26317363
DOI: 10.1371/journal.pone.0136910