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Sleep & Breathing = Schlaf & Atmung Mar 2008Residual excessive sleepiness (ES) and impaired cognition can occur despite effective and regular nasal continuous positive airway pressure (nCPAP) therapy in some...
Residual excessive sleepiness (ES) and impaired cognition can occur despite effective and regular nasal continuous positive airway pressure (nCPAP) therapy in some patients with obstructive sleep apnea (OSA). A pooled analysis of two 12-week, randomized, double-blind studies in nCPAP-adherent patients with ES associated with OSA evaluated the effect of armodafinil on wakefulness and cognition. Three hundred and ninety-one patients received armodafinil (150 or 250 mg) and 260 patients received placebo once daily for 12 weeks. Efficacy assessments included the Maintenance of Wakefulness Test (MWT), Cognitive Drug Research cognitive performance battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. Adverse events were monitored. Armodafinil increased mean MWT sleep latency from baseline to final visit by 2.0 min vs a decrease of 1.5 min with placebo (P < 0.0001). Compared with placebo, armodafinil significantly improved quality of episodic secondary memory (P < 0.05) and patients' ability to engage in activities of daily living (P < 0.0001) and reduced fatigue (P < 0.01). The most common adverse events were headache, nausea, and insomnia. Armodafinil did not adversely affect desired nighttime sleep, and nCPAP use remained high (approximately 7 h/night). Adjunct treatment with armodafinil significantly improved wakefulness, long-term memory, and patients' ability to engage in activities of daily living in nCPAP-adherent individuals with ES associated with OSA. Armodafinil also reduced patient-reported fatigue and was well tolerated.
Topics: Adult; Attention; Benzhydryl Compounds; Central Nervous System Stimulants; Cognition Disorders; Combined Modality Therapy; Continuous Positive Airway Pressure; Disorders of Excessive Somnolence; Double-Blind Method; Female; Humans; Male; Memory, Short-Term; Meta-Analysis as Topic; Middle Aged; Modafinil; Multicenter Studies as Topic; Neuropsychological Tests; Psychometrics; Randomized Controlled Trials as Topic; Reaction Time; Retention, Psychology; Sleep Apnea, Obstructive; Wakefulness
PubMed: 17874255
DOI: 10.1007/s11325-007-0137-7 -
Pharmacological Reviews 2014Psychostimulants such as cocaine have been used as performance enhancers throughout recorded history. Although psychostimulants are commonly prescribed to improve... (Review)
Review
Psychostimulants such as cocaine have been used as performance enhancers throughout recorded history. Although psychostimulants are commonly prescribed to improve attention and cognition, a great deal of literature has described their ability to induce cognitive deficits, as well as addiction. How can a single drug class be known to produce both cognitive enhancement and impairment? Properties of the particular stimulant drug itself and individual differences between users have both been suggested to dictate the outcome of stimulant use. A more parsimonious alternative, which we endorse, is that dose is the critical determining factor in cognitive effects of stimulant drugs. Herein, we review several popular stimulants (cocaine, amphetamine, methylphenidate, modafinil, and caffeine), outlining their history of use, mechanism of action, and use and abuse today. One common graphic depiction of the cognitive effects of psychostimulants is an inverted U-shaped dose-effect curve. Moderate arousal is beneficial to cognition, whereas too much activation leads to cognitive impairment. In parallel to this schematic, we propose a continuum of psychostimulant activation that covers the transition from one drug effect to another as stimulant intake is increased. Low doses of stimulants effect increased arousal, attention, and cognitive enhancement; moderate doses can lead to feelings of euphoria and power, as well as addiction and cognitive impairment; and very high doses lead to psychosis and circulatory collapse. This continuum helps account for the seemingly disparate effects of stimulant drugs, with the same drug being associated with cognitive enhancement and impairment.
Topics: Animals; Benzhydryl Compounds; Caffeine; Central Nervous System Stimulants; Cocaine; Cognition; Humans; Methamphetamine; Methylphenidate; Modafinil
PubMed: 24344115
DOI: 10.1124/pr.112.007054 -
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 -
Nature and Science of Sleep 2010Excessive sleepiness (ES) is a widespread condition, commonly the result of a sleep/ wake disorder such as obstructive sleep apnea (OSA), shift-work disorder (SWD), or...
Excessive sleepiness (ES) is a widespread condition, commonly the result of a sleep/ wake disorder such as obstructive sleep apnea (OSA), shift-work disorder (SWD), or narcolepsy. ES poses significant health and safety concerns in patients. Numerous interventions are available to treat the underlying causes of ES and ES itself, including behavioral measures, mechanical devices, and pharmacologic agents. This review explores the evidence supporting the use of armodafinil to treat ES associated with OSA, SWD, and narcolepsy. Armodafinil is an oral non-amphetamine wake-promoting agent, the R-isomer of racemic modafinil. Armodafinil and modafinil share many clinical and pharmacologic properties and are distinct from central nervous system stimulants; however, the mechanisms of action of modafinil and armodafinil are poorly characterized. Compared with modafinil, the wake-promoting effects of armodafinil persist later in the day. It is for this reason that armodafinil may be a particularly appropriate therapy for patients with persistent ES due to OSA, SWD, or narcolepsy.
PubMed: 23616702
DOI: 10.2147/nss.s6728 -
Journal of the Neurological Sciences Oct 2018Concurrent use of modafinil or armodafinil with monoamine oxidase inhibitors (MAOIs) is contraindicated due to a theoretical risk of drug synergism and acute... (Review)
Review
Concurrent use of modafinil or armodafinil with monoamine oxidase inhibitors (MAOIs) is contraindicated due to a theoretical risk of drug synergism and acute hypertensive episodes. However, few data are available to substantiate that risk, and several case studies have suggested that the combination is safe. To our knowledge, we present the first case of a patient treated concurrently with armodafinil and tranylcypromine. The patient developed an acute hypertensive crisis with severe headache, nausea, blurry vision, and neck stiffness. Her symptoms corresponded with the predicted pharmacokinetic and pharmacodynamic response. She was also taking brexpiprazole, which could have contributed to her underlying symptoms. However, limited data suggest that the single combination of brexpiprazole with armodafinil or MAOIs would be safe. Upon review of the literature, two out of seven patients, including our own, treated concurrently with modafinil or armodafinil and an MAOI developed an adverse reaction. Physicians should exercise caution if using these classes of drugs together.
Topics: Adult; Drug Synergism; Drug Therapy, Combination; Female; Headache; Humans; Hypertension; Modafinil; Monoamine Oxidase Inhibitors; Tranylcypromine; Wakefulness-Promoting Agents
PubMed: 30077942
DOI: 10.1016/j.jns.2018.07.023 -
Sleep Medicine Reviews Jun 2013This review considers recent evidence showing that cells in the reticular activating system (RAS) exhibit (1) electrical coupling mainly in GABAergic cells, and (2)... (Review)
Review
This review considers recent evidence showing that cells in the reticular activating system (RAS) exhibit (1) electrical coupling mainly in GABAergic cells, and (2) gamma band activity in virtually all of the cells. Specifically, cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine dorsal subcoeruleus nucleus dorsalis (SubCD) (1) show electrical coupling, and (2) all fire in the beta/gamma band range when maximally activated, but no higher. The mechanism behind electrical coupling is important because the stimulant modafinil was shown to increase electrical coupling. We also provide recent findings demonstrating that all cells in the PPN and Pf have high threshold, voltage-dependent P/Q-type calcium channels that are essential to gamma band activity. On the other hand, all SubCD, and some PPN, cells manifested sodium-dependent subthreshold oscillations. A novel mechanism for sleep-wake control based on transmitter interactions, electrical coupling, and gamma band activity is described. We speculate that continuous sensory input will modulate coupling and induce gamma band activity in the RAS that could participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions.
Topics: Animals; Awareness; Benzhydryl Compounds; Beta Rhythm; Calcium Channels; Central Nervous System Stimulants; Cerebral Cortex; Electroencephalography; Humans; Intralaminar Thalamic Nuclei; Locus Coeruleus; Modafinil; Neural Pathways; Neurons; Pedunculopontine Tegmental Nucleus; Pons; Reticular Formation; Signal Processing, Computer-Assisted; Sleep; Sodium Channels; Synaptic Transmission; Wakefulness; gamma-Aminobutyric Acid
PubMed: 23044219
DOI: 10.1016/j.smrv.2012.06.002 -
The Psychiatric Clinics of North America Jun 2012The use of stimulant medications for the treatment of cocaine dependence is an evolving scientific line of research. To date, the most promising results are with the... (Review)
Review
The use of stimulant medications for the treatment of cocaine dependence is an evolving scientific line of research. To date, the most promising results are with the higher-potency medications, the amphetamine analogues, or a combination of a dopaminergic medication with a contingency management behavioral intervention. The development of effective pharmacotherapies for opioid and nicotine dependence using an agonist replacement approach suggests that these promising findings needs to continue to be vigorously investigated. In clinical trial reports, there are very few instances of cardiovascular adverse events, which suggests that for well-selected patients with cocaine dependence, stimulant replacement therapy can be safe. However, clinical trial eligibility criteria excludes most high-risk patients from participating, and introducing stimulant substitution to the wider treatment community would likely expose more vulnerable patients to the medical risks associated with stimulant treatment while using cocaine. As treatment development research moves forward, attention must be paid to helping clinicians select patients who are most likely to benefit from stimulant substitution treatment and how to identify those at risk. An additional concern with the use of stimulant medication treatment of cocaine dependence is prescribing controlled substances for patients with active substance use disorders. Again, within a clinical trial, medication supplies are monitored and distributed carefully in small quantities. In a community setting, misuse or diversion will be risks associated with prescribing controlled substances to patients with addictive disorders, but therapeutic strategies for monitoring and limiting that risk can be implemented. Psychostimulant pharmacotherapy is a promising line of research for the treatment of cocaine dependence, a condition for which no effective pharmacotherapy has been identified. Further research is required to confirm positive results from single-site trials, in particular the study of amphetamines as a treatment for cocaine dependence. As this literature evolves, strategies to manage the risk of prescribing controlled substances to patients with addictive disorders need to be tested and refined. Biases against using controlled substances as a treatment for cocaine dependence should be challenged, much in the way the use of agonist treatment transformed the treatment of opioid dependence despite initial resistance from the field.
Topics: Amphetamines; Animals; Benzhydryl Compounds; Bupropion; Central Nervous System Stimulants; Clinical Trials as Topic; Cocaine; Cocaine-Related Disorders; Combined Modality Therapy; Dopamine Agents; Humans; Methylphenidate; Modafinil; Placebos; Rats; Reinforcement, Psychology; United States
PubMed: 22640764
DOI: 10.1016/j.psc.2012.03.012 -
Therapeutic Advances in... Jun 2012Schizophrenia is characterized by reality distortion, psychomotor poverty and cognitive disturbances. These characteristics contribute to a lesser social functioning and...
Schizophrenia is characterized by reality distortion, psychomotor poverty and cognitive disturbances. These characteristics contribute to a lesser social functioning and lower quality of life in patients with schizophrenia. It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain. In this paper we review the literature relevant to the question of whether modafinil and armodafinil are beneficial as add-on therapy in antipsychotic-treated patients with schizophrenia. A total of 15 articles were included in this review; of the 15 articles, 10 were randomized controlled trials (RCTs). Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. With respect to cognitive disturbances, animal models of cognitive deficits show clear improvements with modafinil. In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to enhance cognitive function, attenuate fatigue, enhance activity, improve negative symptoms and reduce weight in patients with schizophrenia.
PubMed: 23983964
DOI: 10.1177/2045125312441815 -
Psychosomatics 2011To evaluate the efficacy and safety of armodafinil in the treatment of fatigue in HIV+ patients, and to assess its effect on depressive symptoms and behavior once... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the efficacy and safety of armodafinil in the treatment of fatigue in HIV+ patients, and to assess its effect on depressive symptoms and behavior once fatigue remitted.
METHOD
HIV+ patients with clinically significant fatigue were treated in a placebo-controlled randomized double-blind trial for 4 weeks. Armodafinil responders and placebo non-responders or relapsers were treated openly for a total of 16 weeks with armodafinil. The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement Scale, supplemented by the Fatigue Severity Scale, the Hamilton Depression Rating Scale, and the Beck Depression Inventory. Safety was assessed with assays of CD4 cell count and HIV RNA viral load and the SAFTEE side effects rating scale. Maximum trial dose of armodafinil was 250 mg/d.
RESULTS
Seventy patients were enrolled. Attrition was 9%. In intention-to-treat analyses, fatigue response rate to armodafinil was 75% and to placebo, 26%. Armodafinil did not reduce depressive symptoms in the absence of improved energy, but of those patients with an Axis I depressive disorder at study entry whose energy improved, 82% experienced improved mood as well. Markers of immunologic suppression did not change during treatment. At 6 months, those still taking armodafinil had more energy and fewer depressive symptoms than those who were no longer taking it.
CONCLUSIONS
As we found in our RCT of modafinil, armodafinil appears effective and well tolerated in treating fatigue in HIV+ patients. Side effects were minimal and most patients reported substantially improved energy and mood.
Topics: Adult; Aged; Benzhydryl Compounds; CD4 Lymphocyte Count; Central Nervous System Stimulants; Depression; Double-Blind Method; Fatigue; Female; HIV Infections; Humans; Male; Middle Aged; Modafinil; Neuropsychological Tests; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 21777715
DOI: 10.1016/j.psym.2011.02.005 -
Sleep Dec 2007The purpose of this paper is to summarize current knowledge about treatment of narcolepsy and other hypersomnias of central origin. (Review)
Review
OBJECTIVE
The purpose of this paper is to summarize current knowledge about treatment of narcolepsy and other hypersomnias of central origin.
METHODS
The task force performed a systematic and comprehensive review of the relevant literature and graded the evidence using the Oxford grading system. This paper discusses the strengths and limitations of the available evidence regarding treatment of these conditions, and summarizes key information about safety of these medications. Our findings provide the foundation for development of evidence-based practice parameters on this topic by the Standards of Practice Committee of the American Academy of Sleep Medicine.
RESULTS
The majority of recent papers in this field provide information about use of modafinil or sodium oxybate for treatment of sleepiness associated with narcolepsy. Several large randomized, placebo-controlled studies indicate that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. We identified no studies that report direct comparison of these newer medications versus traditional stimulants, or that indicate what proportion of patients treated initially with these medications require transition to traditional stimulants or to combination therapy to achieve adequate alertness. As with the traditional stimulants, modafinil and sodium oxybate provide, at best, only moderate improvement in alertness rather than full restoration of alertness in patients with narcolepsy. Several large randomized placebo-controlled studies demonstrate that sodium oxybate is effective for treatment of cataplexy associated with narcolepsy, and earlier studies provide limited data to support the effectiveness of fluoxetine and tricyclic antidepressants for treatment of cataplexy. Our findings indicate that very few reports provide information regarding treatment of special populations such as children, older adults, and pregnant or breastfeeding women. The available literature provides a modest amount of information about improvement in quality of life in association with treatment, patient preferences among the different medications, or patient compliance.
CONCLUSION
Several recent studies provide evidence that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. No studies were identified that report direct comparison of these newer medications with traditional stimulants. Despite significant advances in understanding the pathophysiology of narcolepsy, we do not have an ideal treatment to restore full and sustained alertness. Future investigations should be directed toward development of more effective and better tolerated therapies, and primary prevention.
Topics: Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Cataplexy; Central Nervous System Stimulants; Disorders of Excessive Somnolence; Evidence-Based Medicine; Fluoxetine; Humans; Modafinil; Narcolepsy; Randomized Controlled Trials as Topic; Sodium Oxybate
PubMed: 18246981
DOI: 10.1093/sleep/30.12.1712