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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 -
European Journal of Cancer Care Nov 2016Cancer-related fatigue (CRF) is a common symptom affecting 60-90% of cancer survivors, and effective management for CRF is not yet available. Recently, an increasing... (Meta-Analysis)
Meta-Analysis Review
Cancer-related fatigue (CRF) is a common symptom affecting 60-90% of cancer survivors, and effective management for CRF is not yet available. Recently, an increasing number of trials examining the use of psychotropic drugs for the treatment of CRF have been performed, but these trials have yielded inconsistent results. Therefore, we conducted a meta-analysis aimed at assessing the effect and safety of psychotropic drugs for the management of CRF. Ten eligible trials of the psychotropic drugs methylphenidate and modafinil in a total of 1582 participants treated for CRF were subjected to statistical analyses. A meta-analysis of seven of these studies indicated that methylphenidate was superior to placebo for the treatment of CRF. Another meta-analysis of three studies evaluating modafinil found that this drug was no better than placebo. Adverse events were similar between both methylphenidate and modafinil and the placebo groups. Our meta-analysis indicated that the treatment of CRF with methylphenidate appears to be effective, whereas modafinil provides no benefit. These results of this analysis warrant further trials to confirm the efficacy and safety of psychotropic drugs for the treatment of CRF.
Topics: Benzhydryl Compounds; Fatigue; Humans; Methylphenidate; Modafinil; Neoplasms; Psychotropic Drugs
PubMed: 26490083
DOI: 10.1111/ecc.12397 -
Bipolar Disorders Mar 2020The aim of this study was to evaluate the efficacy and safety of the dopaminergic-enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to evaluate the efficacy and safety of the dopaminergic-enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression.
METHODS
A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP-I) or bipolar II (BP-II) depression. Data for response/remission and all-cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model.
RESULTS
Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP-I patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I = 34%, P = .19; I = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01-1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10-1.73; P = .005). All-cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89-1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39-2.5; P = .98; RR, 1.02; 95% CI, 0.37-2.85; P = .97).
CONCLUSION
This narrower scope meta-analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic-enhancing agents are encouraged.
Topics: Bipolar Disorder; Female; Humans; Modafinil; Randomized Controlled Trials as Topic
PubMed: 31643130
DOI: 10.1111/bdi.12859 -
PloS One 2013Modafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Modafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder and obstructive sleep apnea. Existing trials of modafinil for fatigue and EDS associated with neurological disorders provided inconsistent results. This meta-analysis was aimed to assess drug safety and effects of modafinil on fatigue and EDS associated with neurological disorders.
METHODS
A comprehensive literature review was conducted in order to identify published studies assessing the effects of modafinil on fatigue and EDS associated with neurological disorders. Primary outcomes included fatigue and EDS. Secondary outcomes included depression and adverse effects.
FINDINGS
Ten randomized controlled trials were identified including 4 studies of Parkinson's disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and 1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82 95% CI -1.54 - -0.11 p=0.02, I(2)=0%), while a beneficial effect of modafinil on fatigue was not confirmed in the pooled studies of PD or MS. Treatment results demonstrated a clear beneficial effect of modafinil on EDS in patients with PD (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I(2)=14%), but not with MS and TBI. No difference was seen between modafinil and placebo treatments in patients with PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events were similar between modafinil and placebo groups except that more patients were found with insomnia and nausea in modafinil group.
CONCLUSIONS
Existing trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.
Topics: Benzhydryl Compounds; Depression; Disorders of Excessive Somnolence; Fatigue; Humans; Modafinil
PubMed: 24312590
DOI: 10.1371/journal.pone.0081802 -
Schizophrenia Research Jul 2013Primary negative symptoms of schizophrenia (NSS) contribute heavily to functional disability and treatment of these symptoms continues to be a major unmet need even when... (Review)
Review
BACKGROUND
Primary negative symptoms of schizophrenia (NSS) contribute heavily to functional disability and treatment of these symptoms continues to be a major unmet need even when the positive (psychotic) symptoms are controlled. The modified dopamine (DA) hypothesis posits that positive symptoms are associated with increased DA activity in the mesolimbic tract whereas NSS and cognitive symptoms are associated with decreased DA activity in the mesocortical (frontal) region. Several studies have reported improvement in NSS with DA agonist use, but with varying degrees of risk for triggering psychotic symptoms, especially in the absence of concurrent antipsychotic drug treatment. This article aims to examine older and newer evidence suggesting that psychostimulants may have a potential therapeutic role in the treatment of NSS together with a thorough review of the potential risks and benefits of psychostimulant administration in individuals with schizophrenia.
METHODS
A systematic search of relevant literature using electronic databases, reference lists, and data presented at recent meetings was conducted.
RESULTS
Improvement of NSS after psychostimulant administration is reviewed both in challenge and treatment paradigms with various agents such as methylphenidate, amphetamine, and modafinil or armodafinil. The literature points to evidence that, used adjunctively, DA agonists may improve NSS without worsening of positive symptoms in selected patients who are stable and treated with effective antipsychotic medications. Several areas of inadequate study and limitations are identified including small study samples, single-site trials, varying rigor of bias control, the dose and the duration of adjunctive psychostimulant administration, and the potential for development of tolerance.
CONCLUSION
Large, controlled clinical trials to further characterize effects of psychostimulants on NSS in carefully selected patients are warranted.
Topics: Antipsychotic Agents; Central Nervous System Stimulants; Databases, Bibliographic; Dopamine; Humans; Schizophrenia
PubMed: 23619055
DOI: 10.1016/j.schres.2013.03.019 -
Pharmacopsychiatry Apr 2020Several reports of the effectiveness of the use of psychostimulants for the treatment of Alzheimer's disease (AD) are available. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several reports of the effectiveness of the use of psychostimulants for the treatment of Alzheimer's disease (AD) are available.
METHODS
A systematic review and meta-analysis was conducted including double-blind, randomized, placebo-controlled trials. Outcomes were the improvement of apathy scales score (primary), mini-mental state examination (MMSE) score, activities of daily living scale score, Zarit burden interview score, all-cause discontinuation, discontinuation due to adverse events, and incidence of at least 1 adverse event.
RESULTS
Three methylphenidate studies and 1 modafinil study were identified (n=156). Results from combined psychostimulants were superior to placebo in the improvement of apathy scales score (standardized mean differences [SMD]=-0.63 (-1.22, -0.04), p=0.04, all studies) and the MMSE score (SMD=-0.58 (-1.14, -0.02), p=0.04, 3 methylphenidate studies). The modafinil study was excluded from the meta-analysis for the improvement of apathy scales score; therefore, the effect size increased (SMD=-0.82 (-1.43, -0.20), p=0.009). However, no significant differences were observed in terms of other outcomes, including safety outcomes between the treatment groups.
DISCUSSION
Methylphenidate would be effective in treating apathy and cognitive impairment in AD patients.
Topics: Aged; Alzheimer Disease; Apathy; Central Nervous System Stimulants; Cognitive Dysfunction; Double-Blind Method; Humans; Methylphenidate; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32000270
DOI: 10.1055/a-1076-8228 -
Therapeutic Drug Monitoring Apr 2020The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among...
BACKGROUND
The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B) fall in the top 10 most used new psychoactive substances (NPSs) among high-risk substance users. Various phenethylamines and NPS are also highly used in populations with mental disorders, depression, or attention deficit hyperactivity disorder (ADHD). Moreover, NPS use is highly prevalent among men and women with risky sexual behavior. Considering these specific populations and their frequent concurrent use of drugs, such as antidepressants, ADHD medication, and antiretrovirals, reports on potential interactions between these drugs, and phenethylamines 4-FA and 2C-B, were reviewed.
METHODS
The authors performed a systematic literature review on 4-FA and 2C-B interactions with antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, bupropion, venlafaxine, phenelzine, moclobemide, and tranylcypromine), ADHD medications (atomoxetine, dexamphetamine, methylphenidate, and modafinil), and antiretrovirals.
RESULTS
Limited literature exists on the pharmacokinetics and drug-drug interactions of 2C-B and 4-FA. Only one case report indicated a possible interaction between 4-FA and ADHD medication. Although pharmacokinetic interactions between 4-FA and prescription drugs remain speculative, their pharmacodynamic points toward interactions between 4-FA and ADHD medication and antidepressants. The pharmacokinetic and pharmacodynamic profile of 2C-B also points toward such interactions, between 2C-B and prescription drugs such as antidepressants and ADHD medication.
CONCLUSIONS
A drug-drug (phenethylamine-prescription drug) interaction potential is anticipated, mainly involving monoamine oxidases for 2C-B and 4-FA, with monoamine transporters being more specific to 4-FA.
Topics: Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Depressive Disorder; Dimethoxyphenylethylamine; Drug Interactions; Humans; Phenethylamines; Prescription Drugs
PubMed: 32022784
DOI: 10.1097/FTD.0000000000000725 -
The Cochrane Database of Systematic... Feb 2011Postpolio syndrome (PPS) may affect survivors of paralytic poliomyelitis and is characterised by a complex of neuromuscular symptoms leading to a decline in physical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpolio syndrome (PPS) may affect survivors of paralytic poliomyelitis and is characterised by a complex of neuromuscular symptoms leading to a decline in physical functioning. The effectiveness of pharmacological treatment and rehabilitation management in PPS is not yet established.
OBJECTIVES
To review systematically the effects of any treatment for PPS compared to placebo, usual care or no treatment.
SEARCH STRATEGY
We searched the following databases on 1 October 2010: Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO and CINAHL Plus from inception to September 2010.
SELECTION CRITERIA
Randomised and quasi-randomised trials of any form of pharmacological or non-pharmacological treatment for people with PPS. The primary outcome was self-perceived activity limitations and secondary outcomes were muscle strength, muscle endurance, fatigue, pain and adverse events.
DATA COLLECTION AND ANALYSIS
Two authors independently selected eligible studies, assessed risk of bias and extracted data.
MAIN RESULTS
Nine pharmacological (modafinil, intravenous immunoglobulin, pyridostigmine, lamotrigine, amantadine, prednisone) and three non-pharmacological (muscle strengthening, rehabilitation in a warm climate (i.e. temperature ± 25°C, dry and sunny) and a cold climate (i.e. temperature ± 0°C, rainy or snowy), static magnetic fields) studies were included in this review. None of the included studies was completely free from any risk of bias and the most prevalent risk of bias was lack of blinding.There is moderate quality evidence that intravenous immunoglobulin has no beneficial effect on activity limitations and there is inconsistency in the evidence for effectiveness on muscle strength and pain. Results of one trial provide very low quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations. Data from two single trials suggest that muscle strengthening of thumb muscles (very low quality evidence) and static magnetic fields (moderate quality evidence) are beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. Finally, there is evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS.
AUTHORS' CONCLUSIONS
Due to insufficient good quality data and lack of randomised studies it is impossible to draw definite conclusions on the effectiveness of interventions for PPS. Results indicate that IVIG, lamotrigine, muscle strengthening exercises and static magnetic fields may be beneficial but need further investigation.
Topics: Cold Temperature; Exercise Therapy; Hot Temperature; Humans; Immunoglobulins, Intravenous; Lamotrigine; Muscle Fatigue; Muscle Strength; Postpoliomyelitis Syndrome; Randomized Controlled Trials as Topic; Triazines
PubMed: 21328301
DOI: 10.1002/14651858.CD007818.pub2 -
Drug and Alcohol Dependence Oct 2018Demand for treatment for amphetamine use is increasing internationally. Establishing effective pharmacotherapy provides broader treatment options for people who are... (Review)
Review
BACKGROUND
Demand for treatment for amphetamine use is increasing internationally. Establishing effective pharmacotherapy provides broader treatment options for people who are dependent on amphetamine and may encourage engagement in evidence-based behavioral treatment. This study aimed to identify medicines that have potential in improving treatment outcomes for people who are dependent on amphetamines.
METHODS
Medline, PsycINFO, Embase and the Cochrane Database of Systematic Reviews were searched from 1997 to 2012 and again from 2013 to 2016. Studies on medications for amphetamine/methamphetamine dependence treatment were selected and assessed by two independent researchers. A meta-narrative review approach was used to synthesize results.
RESULTS
A total of 49 studies investigating 20 potential pharmacotherapies were eligible for inclusion. Of these, 35 studies related to 33 level II quality randomized controlled trials (RCTs). Five medications were subject to multiple RCTs. Four of these medicines demonstrated some limited evidence of benefit for reducing amphetamine use: methylphenidate (as reported in three studies), bupropion (in three studies), modafinil (two studies), and naltrexone (one study). Four RCTs of dexamphetamine suggest its benefit on secondary outcomes such as treatment retention, but not for reducing amphetamine use. Six other medicines indicate the potential for efficacy, but the number of studies is too small to draw conclusions.
CONCLUSIONS
No medicine has as yet demonstrated sufficient, consistent evidence of effectiveness to support its use in routine treatment. High study drop-out and poor medication adherence limits the strength of evidence and raises important clinical questions about how to improve treatment engagement and outcomes.
Topics: Amphetamine; Amphetamine-Related Disorders; Dextroamphetamine; Humans; Medication Adherence; Methylphenidate; Modafinil; Naltrexone; Randomized Controlled Trials as Topic
PubMed: 30173086
DOI: 10.1016/j.drugalcdep.2018.06.038 -
The Journal of Clinical Psychiatry Apr 2006Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy and shift work sleep disorder and as adjunctive treatment of... (Review)
Review
BACKGROUND
Modafinil is a novel wake-promoting agent that has U.S. Food and Drug Administration approval for narcolepsy and shift work sleep disorder and as adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. Modafinil has a novel mechanism and is theorized to work in a localized manner, utilizing hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate. It is a well-tolerated medication with low propensity for abuse and is frequently used for off-label indications. The objective of this study was to systematically review the available evidence supporting the clinical use of modafinil.
DATA SOURCES
The search term modafinil OR Provigil was searched on PubMed. Selected articles were mined for further potential sources of data. Abstracts from major scientific conferences were reviewed. Lastly, the manufacturer of modafinil in the United States was asked to provide all publications, abstracts, and unpublished data regarding studies of modafinil.
DATA SYNTHESIS
There have been 33 double-blind, placebo-controlled trials of modafinil. Additionally, numerous smaller studies have been performed, and case reports of modafinil's use abound in the literature.
CONCLUSIONS
Modafinil is a promising drug with a large potential for many uses in psychiatry and general medicine. Treating daytime sleepiness is complex, and determining the precise nature of the sleep disorder is vital. Modafinil may be an effective agent in many sleep conditions. To date, the strongest evidence among off-label uses exists for the use of modafinil in attention-deficit disorder, postanesthetic sedation, and cocaine dependence and withdrawal and as an adjunct to antidepressants for depression.
Topics: Animals; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Brain Chemistry; Central Nervous System Stimulants; Cocaine-Related Disorders; Depressive Disorder; Drug Therapy, Combination; Humans; Mice; Modafinil; Randomized Controlled Trials as Topic; Rats; Sleep Wake Disorders
PubMed: 16669720
DOI: 10.4088/jcp.v67n0406