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CNS Drugs Sep 2009Armodafinil is the R-enantiomer of modafinil, a wake-promoting agent, that primarily affects areas of the brain involved in controlling wakefulness. Once-daily... (Review)
Review
Armodafinil is the R-enantiomer of modafinil, a wake-promoting agent, that primarily affects areas of the brain involved in controlling wakefulness. Once-daily armodafinil was effective in improving wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome (OSA) [despite treatment of the underlying condition], narcolepsy or shift work sleep disorder (SWSD) in four large (n > 195), double-blind, multinational trials of 12 weeks' duration. Compared with placebo, mean sleep latency (coprimary endpoint) was significantly improved with armodafinil 150 or 250 mg once daily in patients with OSA or narcolepsy, and with armodafinil 150 mg once daily in patients with SWSD, as assessed by the Multiple Sleep Latency Test (MSLT) or the Maintenance of Wakefulness Test (MWT). Furthermore, a significantly higher proportion of armodafinil than placebo recipients achieved a response (at least a minimal improvement) on the Clinical Global Impressions of Change (CGI-C) scale at study end in these four trials (coprimary endpoint). Once-daily armodafinil was generally well tolerated in adult patients with excessive sleepiness associated with OSA (despite treatment of the underlying condition), narcolepsy or SWSD.
Topics: Benzhydryl Compounds; Central Nervous System Stimulants; Clinical Trials as Topic; Humans; Modafinil; Narcolepsy; Sleep Apnea, Obstructive; Sleep Disorders, Circadian Rhythm; Stereoisomerism; Wakefulness
PubMed: 19689169
DOI: 10.2165/11203290-000000000-00000 -
Journal of Human Lactation : Official... May 2023
Topics: Female; Humans; Animals; Modafinil; Milk; Breast Feeding; Psychiatric Status Rating Scales; Benzhydryl Compounds; Double-Blind Method; Central Nervous System Stimulants; Treatment Outcome
PubMed: 37073877
DOI: 10.1177/08903344231156361 -
Expert Opinion on Pharmacotherapy Apr 2010Excessive sleepiness causes impaired quality of life and increases the risk of poor health and accidents. Armodafinil is a wake-promoting agent approved in 2007 by the... (Review)
Review
IMPORTANCE OF THE FIELD
Excessive sleepiness causes impaired quality of life and increases the risk of poor health and accidents. Armodafinil is a wake-promoting agent approved in 2007 by the US Food and Drug Administration for the treatment of excessive sleepiness arising from narcolepsy, obstructive sleep apnea (OSA; even after optimal treatment for the underlying obstruction) and shift-work disorder (SWD). It is the R-enantiomer of modafinil, which is a racemic mixture of R- and S-enantiomers.
AREAS COVERED IN THIS REVIEW
This review summarizes the recent primary data on the pharmacokinetics, clinical efficacy and safety of armodafinil using literature published since 2005 that was identified from PubMed.
WHAT THE READER WILL GAIN
The review describes recent advances in the understanding of the pharmacokinetic profile of the drug and why this may improve wakefulness later after dosing compared with modafinil. It also describes the recent efficacy and safety data supporting the use of armodafinil to treat excessive sleepiness in indicated patients.
TAKE HOME MESSAGE
Armodafinil is a useful therapy for the treatment of excessive sleepiness arising from a number of clinical conditions. It is generally well tolerated and has a low potential for abuse or tolerance.
Topics: Animals; Benzhydryl Compounds; Central Nervous System Stimulants; Disorders of Excessive Somnolence; Humans; Modafinil; Sleep; Treatment Outcome; Wakefulness
PubMed: 20307223
DOI: 10.1517/14656561003705738 -
The European Respiratory Journal May 2016Modafinil is used internationally to treat residual sleepiness despite continuous positive airway pressure in obstructive sleep apnoea (res-OSA). In 2011, the European... (Meta-Analysis)
Meta-Analysis Review
Modafinil is used internationally to treat residual sleepiness despite continuous positive airway pressure in obstructive sleep apnoea (res-OSA). In 2011, the European Medicines Agency removed the indication based on an unfavourable risk-benefit profile in two trials for efficacy and all accumulated safety data. We performed a meta-analysis of all randomised controlled trials of modafinil (or armodafinil) in res-OSA to quantify efficacy and safety.We systematically searched and assessed studies from major databases, conferences and trials registries to find randomised, placebo-controlled trials of modafinil/armodafinil for ≥2 weeks in adult res-OSA treating sleepiness.We analysed 10 of the 232 articles identified that met inclusion criteria (1466 patients). Modafinil/armodafinil improved the Epworth Sleepiness Scale score (2.2 points, 95% CI 1.5-2.9) and the Maintenance of Wakefulness Test over placebo (3 min, 95% CI 2.1-3.8 min). Modafinil/armodafinil tripled adverse events and doubled adverse events leading to withdrawal but did not increase serious adverse events (hospitalisations or death).Modafinil and armodafinil improve subjective and objective daytime sleepiness in res-OSA. We believe our analysis is a fairer analysis of the risk-benefit profile of this indication. Clinicians may want to use this data to balance the risks and benefits on a case-by-case basis with their patients.
Topics: Adult; Benzhydryl Compounds; Central Nervous System Stimulants; Continuous Positive Airway Pressure; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Modafinil; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Sleep Stages; Sleep Wake Disorders; Treatment Outcome; Wakefulness; Wakefulness-Promoting Agents
PubMed: 26846828
DOI: 10.1183/13993003.01509-2015 -
Annals of Clinical Psychiatry :... Aug 2023Bipolar depression is a serious neuropsychiatric disorder associated with a high risk of morbidity and suicidality. Standard antidepressants approved for treating major...
BACKGROUND
Bipolar depression is a serious neuropsychiatric disorder associated with a high risk of morbidity and suicidality. Standard antidepressants approved for treating major depressive disorder fail to exert efficacy in bipolar depression. Although 5 agents have been developed for the treatment of bipolar depression, treatment resistance is still observed in some patients, and requires off-label pharmacotherapy. Modafinil and armodafinil have been reported to improve treatment-resistant bipolar depression, but with inconsistent results.
METHODS
We present a case of a 65-year-old woman with severe bipolar depression who failed to respond to electroconvulsive therapy and IV ketamine but later responded to high-dose armodafanil.
RESULTS
The patient responded to high-dose armodafinil (gradually titrated to 1,000 mg/d) and achieved remission with good tolerability for 5 years. Recently, she contracted COVID-19 and developed muscular weakness. After a lengthy workup, we became concerned for myopathy as an adverse effect from armodafinil. The patient's dose of armodafinil was significantly reduced and she subsequently became very depressed and functionally disabled before improving again when armodafinil 1,000 mg/d was reinstated.
CONCLUSIONS
We propose that some of the negative results seen in research of armodafinil for bipolar depression may be due to the use of low doses (100 to 200 mg/d), and higher doses may be needed for adequate response in treatment-resistant bipolar depression.
Topics: Female; Humans; Aged; Modafinil; Bipolar Disorder; Depressive Disorder, Major; Benzhydryl Compounds; COVID-19
PubMed: 37459498
DOI: 10.12788/acp.0113 -
Drugs Apr 2022'Smart drugs' (also known as 'nootropics' and 'cognitive enhancers' [CEs]) are being used by healthy subjects (i.e. students and workers) typically to improve memory,... (Review)
Review
'Smart drugs' (also known as 'nootropics' and 'cognitive enhancers' [CEs]) are being used by healthy subjects (i.e. students and workers) typically to improve memory, attention, learning, executive functions and vigilance, hence the reference to a 'pharmaceutical cognitive doping behaviour'. While the efficacy of known CEs in individuals with memory or learning deficits is well known, their effect on non-impaired brains is still to be fully assessed. This paper aims to provide an overview on the prevalence of use; putative neuroenhancement benefits and possible harms relating to the intake of the most popular CEs (e.g. amphetamine-type stimulants, methylphenidate, donepezil, selegiline, modafinil, piracetam, benzodiazepine inverse agonists, and unifiram analogues) in healthy individuals. CEs are generally perceived by the users as effective, with related enthusiastic anecdotal reports; however, their efficacy in healthy individuals is uncertain and any reported improvement temporary. Conversely, since most CEs are stimulants, the related modulation of central noradrenaline, glutamate, and dopamine levels may lead to cardiovascular, neurological and psychopathological complications. Furthermore, use of CEs can be associated with paradoxical short- and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. Finally, the non-medical use of any potent psychotropic raises serious ethical and legal issues, with nootropics having the potential to become a major public health concern. Further studies investigating CE-associated social, psychological, and biological outcomes are urgently needed to allow firm conclusions to be drawn on the appropriateness of CE use in healthy individuals.
Topics: Brain; Central Nervous System Stimulants; Cognition; Humans; Methylphenidate; Modafinil; Nootropic Agents
PubMed: 35366192
DOI: 10.1007/s40265-022-01701-7 -
Drugs of Today (Barcelona, Spain : 1998) Jun 2008Armodafinil is the (R)-enantiomer of the wakepromoting compound modafinil (racemic), with a considerably longer half-life of 10-15 hours. Armodafinil (developed by... (Review)
Review
Armodafinil is the (R)-enantiomer of the wakepromoting compound modafinil (racemic), with a considerably longer half-life of 10-15 hours. Armodafinil (developed by Cephalon, Frazer, PA, USA) was approved in June 2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea syndrome and shift work disorder, and the indications are the same as those for modafinil. Like modafinil, the mechanisms of action of armodafinil are not fully characterized and are under debate. Clinical trials in these sleep disorders demonstrated an enhanced efficacy for wake promotion (wake sustained for a longer time period using doses lower than those of modafinil). The safety profile is consistent with that of modafinil, and armodafinil is well tolerated by the patients. Like modafinil, armodafinil is classified as a non-narcotic Schedule IV compound. Many patients with excessive sleepiness may prefer the longer duration of effect and may have better compliance (with low doses) with armodafinil. The commercial challenge to armodafinil may come from generic modafinil, which may become available in 2012, as well as from classical amphetamine and amphetamine-like compounds (for the treatment of narcolepsy).
Topics: Animals; Benzhydryl Compounds; Central Nervous System Stimulants; Humans; Modafinil; Narcolepsy; Sleep Apnea, Obstructive; Sleep Disorders, Circadian Rhythm; Sleep Wake Disorders; Wakefulness
PubMed: 18596995
DOI: 10.1358/dot.2008.44.6.1195861 -
The Medical Letter on Drugs and... Aug 2010
Review
Topics: Animals; Benzhydryl Compounds; Disorders of Excessive Somnolence; Humans; Modafinil; Randomized Controlled Trials as Topic; Wakefulness
PubMed: 20697340
DOI: No ID Found -
Expert Opinion on Drug Metabolism &... Sep 2012Bipolar disorder is a psychiatric illness with recurring episodes of mania and depression. Armodafinil , the R-enantiomer of modafinil, approved for treating excessive... (Review)
Review
INTRODUCTION
Bipolar disorder is a psychiatric illness with recurring episodes of mania and depression. Armodafinil , the R-enantiomer of modafinil, approved for treating excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder, is possibly effective as an adjunctive treatment for bipolar depression.
AREAS COVERED
This review covers the pharmacokinetics of armodafinil, with an emphasis on its use in bipolar depression. Its clinical efficacy in the treatment of bipolar depression is evaluated, along with current data regarding its safety and tolerability.
EXPERT OPINION
One placebo-controlled trial is available, in which armodafinil was efficacious as an adjunctive treatment in bipolar depression. Armodafinil shows a linear pharmacokinetic profile over a broad dose range of 50 - 400 mg (maximal plasma concentration and area under concentration-time curve). Compared with modafinil, an equivalent dose of armodafinil attains higher blood concentrations 4 - 6 h post-dose. The possibility of drug interactions is generally low, although interactions have been shown with some drugs used in bipolar disorder, through mild CYP3A4-induction and CYP2C19-inhibition. Armodafinil is well tolerated and presents a possible new treatment option for bipolar depression. However, further investigation is still needed in order to confirm its efficacy and to clarify its role in the treatment of bipolar depression.
Topics: Benzhydryl Compounds; Bipolar Disorder; Central Nervous System Stimulants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Modafinil
PubMed: 22803602
DOI: 10.1517/17425255.2012.708338 -
Journal of Clinical Sleep Medicine :... Mar 2024This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical...
UNLABELLED
This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical significance of this report lies in the fact that armodafinil is known to cause headaches, at least initially. But perhaps through a reduced need for caffeine and/or a regulation of sleep/wake, armodafinil may reduce headache frequency and severity.
CITATION
Barone DA. Headache improves with armodafinil. 2024;20(3):469-470.
Topics: Humans; Modafinil; Narcolepsy; Caffeine; Cataplexy; Headache
PubMed: 37921201
DOI: 10.5664/jcsm.10906