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Sleep Medicine Reviews Apr 2024Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS). Pharmacotherapy offers a potential treatment approach for EDS in OSA patients. This... (Review)
Review
Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS). Pharmacotherapy offers a potential treatment approach for EDS in OSA patients. This systematic review and meta-analysis aimed to assess the efficacy and safety of pharmacological interventions for alleviating EDS in patients with OSA. Following PRISMA guidelines, we included randomized controlled trials investigating pharmacological treatments for EDS in adult OSA until August 2023. We conducted meta-analysis, subgroup, and meta-regression analyses using a random effects model. Finally, a network meta-analysis synthesized direct and indirect evidence, followed by a comprehensive safety analysis. We included 32 articles in the meta-analysis (n = 3357). Pharmacotherapy showed a significant improvement in the Epworth Sleepiness Scale (ESS) score (Mean Difference (MD) -2.73, (95 % Confidence Interval (CI) [-3.25, -2.20], p < 0.01) and Maintenance of Wakefulness Test (MWT) score (MD 6.00 (95 % CI [2.66, 9.33] p < 0.01). Solriamfetol, followed by Pitolisant and modafinil, exhibited the greatest ESS reduction, while Danavorexton, followed by Solriamfetol and MK-7288, had the strongest impact on MWT. MK-7288 had the most total adverse events (AEs), followed by Danavorexton and armodafinil. Pharmacological Interventions significantly alleviate EDS in OSA patients but with heterogeneity across medications. Treatment decisions should involve a personalized assessment of patient factors and desired outcomes.
PubMed: 38754208
DOI: 10.1016/j.smrv.2024.101934 -
Frontiers in Neurology 2024Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and...
Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.
PubMed: 38562423
DOI: 10.3389/fneur.2024.1321239 -
Bipolar Disorders May 2024Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder... (Review)
Review
Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.
BACKGROUND
Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD.
METHODS
We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials.
RESULTS
Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias.
CONCLUSIONS
Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Cognitive Dysfunction; Central Nervous System Stimulants; Off-Label Use; Methylphenidate
PubMed: 38433530
DOI: 10.1111/bdi.13414 -
Clinical NeuropharmacologyAcute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can...
OBJECTIVES
Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs.
METHODS
This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects.
CONCLUSIONS
The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.
Topics: Humans; Modafinil; Consciousness; Brain Injuries, Traumatic; Amantadine; Brain Injuries; Randomized Controlled Trials as Topic
PubMed: 37962310
DOI: 10.1097/WNF.0000000000000577 -
European Neuropsychopharmacology : the... Jan 2024Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of... (Meta-Analysis)
Meta-Analysis Review
Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms).
Topics: Child; Humans; Adolescent; Depression; Anti-Inflammatory Agents; Minocycline; Pioglitazone; Fatty Acids, Omega-3
PubMed: 37864981
DOI: 10.1016/j.euroneuro.2023.09.006 -
Wellcome Open Research 2021Shift work is essential in society but can be detrimental to health and quality of life and is associated with decreased productivity and increased risk of accidents....
A scoping review of the evidence for the impact of pharmacological and non-pharmacological interventions on shift work related sleep disturbance in an occupational setting.
Shift work is essential in society but can be detrimental to health and quality of life and is associated with decreased productivity and increased risk of accidents. Interventions to reduce these consequences are needed, but the extent and range of trial evidence for interventions for those most affected by their shift-work schedules is unclear. We therefore carried out a scoping review to assess the availability of evidence to inform the development and evaluation of future interventions. We aimed to identify clinical trials of any intervention for shift work-related sleep disturbance that included a comparator group, where the intervention was delivered in an occupational setting. We searched Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL, EMBASE, Medline and Science Citation Index from inception to 30 March 2020 for relevant citations. Citations were screened by two independent reviewers, a third reviewer resolved disagreements. Data were extracted by two independent reviewers. From 1250 unique citations, 14 studies met inclusion criteria for comparative trials of treatment in an occupational setting. There were five trials of hypnotics, five trials of stimulants, and four trials of non-pharmacological therapies (cognitive behavioural therapy, light therapy, aromatherapy and herbal medicine). Outcomes included sleep parameters, day-time sleepiness, and quality of life. There were no consistently reported outcomes across trials. Interventions fell into three distinct groups investigated in distinct time periods without progression from efficacy trials to wider-scale interventions. The lack of consistent patient-reported outcome measures limits synthesising findings. Some trials focussed on optimising sleep, others on reducing wake-time sleepiness. Adequately powered trials of existing interventions are needed, with the development and testing of novel combination treatments in patients with well-defined shift work sleep disorder. A core set of clinically relevant outcomes will develop and standardise the evidence-base for shift work sleep disorder.
PubMed: 37346814
DOI: 10.12688/wellcomeopenres.17002.2 -
Journal of Parkinson's Disease 2023Fatigue is one of the most common and debilitating non-motor symptoms among patients with Parkinson's disease (PD) and significantly impacts quality of life. Therefore,... (Meta-Analysis)
Meta-Analysis
Physical Exercise as a Potential Treatment for Fatigue in Parkinson's Disease? A Systematic Review and Meta-Analysis of Pharmacological and Non-Pharmacological Interventions.
BACKGROUND
Fatigue is one of the most common and debilitating non-motor symptoms among patients with Parkinson's disease (PD) and significantly impacts quality of life. Therefore, effective treatment options are needed.
OBJECTIVE
To provide an update on randomized controlled trials (RCTs) including pharmacological and non-pharmacological (but non-surgical) treatments that examine the effects of fatigue on PD patients.
METHODS
We searched the MEDLINE, EMBASE, PsycINFO, CENTRAL, and CINAHL databases for (cross-over) RCTs on pharmacological and non-pharmacological interventions for treating fatigue in PD patients until May 2021. Meta-analyses for random-effects models were calculated when two or more studies on the same treatment option were available using standardized mean differences (SMDs) with 95% confidence intervals (CIs).
RESULTS
Fourteen pharmacological and 16 non-pharmacological intervention RCTs were identified. For pharmacological approaches, a meta-analysis could only be performed for modafinil compared to placebo (n = 2) revealing a non-significant effect on fatigue (SMD = - 0.21, 95% CI - 0.74-0.31, p = 0.43). Regarding non-pharmacological approaches, physical exercise (n = 8) following different training approaches versus passive or placebo control groups showed a small significant effect (SMD = - 0.37, 95% CI - 0.69- - 0.05, p = 0.02) which could not be demonstrated for acupuncture vs. sham-acupuncture (SMD = 0.16, 95% CI - 0.19-0.50, p = 0.37).
CONCLUSION
Physical exercise may be a promising strategy to treat fatigue in PD patients. Further research is required to examine the efficacy of this treatment strategy and further interventions. Future studies should differentiate treatment effects on physical and mental fatigue as the different underlying mechanisms of these symptoms may lead to different treatment responses. More effort is required to develop, evaluate, and implement holistic fatigue management strategies for PD patients.
Topics: Humans; Parkinson Disease; Exercise; Modafinil; Quality of Life
PubMed: 37334618
DOI: 10.3233/JPD-225116 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887 -
Revista de Neurologia Jun 2023Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms,... (Review)
Review
INTRODUCTION
Psychotic disorders are considered chronic mental health issues. Although it has been demonstrated that these disorders can present with a wide range of symptoms, pharmacological treatment is based on the use of typical and atypical antipsychotics, whose main mechanism of action is dopaminergic blockade, limiting their effect to the improvement of positive symptoms, without improving the rest of the symptoms and giving rise to a large number of serious adverse effects. For this reason, new therapeutic targets other than the dopaminergic system are being studied. The main objective of this review is to test whether these psychoactive substances used in clinical practice could provide additional benefits as an adjunctive treatment for people with psychotic disorders.
DEVELOPMENT
For this systematic review, a literature search was conducted in the databases PsycINFO, Medline, Psicodoc, PubMed and Google Scholar. Altogether 28 articles were included in the review. One of the main findings is that cannabidiol is more effective for improving positive symptoms and psychopathology; modafinil, for cognitive symptoms, motor and emotional functioning and quality of life; and ketamine, for negative symptoms. In addition, all the substances showed a good tolerability and safety profile, especially in comparison to antipsychotics.
CONCLUSION
The results obtained open up the possibility of having a guideline for clinicians/health professionals on the use of cannabidiol, modafinil and ketamine as adjunctive treatment for patients with psychotic conditions.
Topics: Humans; Antipsychotic Agents; Modafinil; Ketamine; Cannabidiol; Quality of Life; Psychotic Disorders
PubMed: 37231549
DOI: 10.33588/rn.7611.2023077 -
Annals of Internal Medicine May 2023Excessive daytime sleepiness (EDS) is common among patients with obstructive sleep apnea (OSA). The comparative effectiveness of pharmacologic agents is unknown. (Meta-Analysis)
Meta-Analysis
Comparative Efficacy and Safety of Wakefulness-Promoting Agents for Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea : A Systematic Review and Network Meta-analysis.
BACKGROUND
Excessive daytime sleepiness (EDS) is common among patients with obstructive sleep apnea (OSA). The comparative effectiveness of pharmacologic agents is unknown.
PURPOSE
To compare the effectiveness of drugs for EDS in OSA using network meta-analysis.
DATA SOURCES
MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov to 7 November 2022.
STUDY SELECTION
Reviewers identified randomized trials that enrolled patients with EDS-associated OSA on or eligible for conventional therapy assigned to any pharmacologic intervention.
DATA EXTRACTION
Paired reviewers independently extracted data addressing effects of drugs on the Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT), and adverse events at the longest reported follow-up. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
DATA SYNTHESIS
Fourteen trials (3085 patients) were eligible. At 4 weeks, compared with placebo, solriamfetol improves ESS scores (mean difference [MD], -3.85 [95% CI, -5.24 to -2.50]; high certainty), and armodafinil-modafinil (MD, -2.25 [CI, -2.85 to -1.64]; moderate certainty) and pitolisant-H3-autoreceptor blockers (MD, -2.78 [CI, -4.03 to -1.51]; moderate certainty) probably improve ESS scores. At 4 weeks, compared with placebo, solriamfetol (standardized mean difference [SMD], 0.9 [CI, 0.64 to 1.17]) and armodafinil-modafinil (SMD, 0.41 [CI, 0.27 to 0.55]) improve MWT (both high certainty), whereas pitolisant-H3-autoreceptor blockers probably do not (moderate certainty). At 4 weeks, armodafinil-modafinil probably increases the risk for discontinuation due to adverse events (relative risk [RR], 2.01 [CI, 1.14 to 3.51]; moderate certainty); solriamfetol may increase the risk for discontinuation due to adverse events (RR, 2.07 [CI, 0.67 to 6.25]; low certainty). Low certainty evidence suggests these interventions may not increase the risk for serious adverse events.
LIMITATIONS
There is limited evidence on long term or effectiveness among patients nonadherent or with mixed adherence to conventional OSA therapies.
CONCLUSION
Solriamfetol, armodafinil-modafinil, and pitolisant reduce daytime sleepiness for patients with OSA already on conventional therapy, with solriamfetol likely superior. Adverse events probably increase the risk for discontinuation of armodafinil-modafinil and may increase the risk for discontinuation with solriamfetol.
PRIMARY FUNDING SOURCE
None.
Topics: Humans; Autoreceptors; Disorders of Excessive Somnolence; Modafinil; Network Meta-Analysis; Sleep Apnea, Obstructive; Wakefulness-Promoting Agents
PubMed: 37155992
DOI: 10.7326/M22-3473