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Journal of Sleep Research Feb 2023Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness,... (Clinical Trial)
Clinical Trial
Armodafinil to reduce the sleepiness related side-effects of sleep restriction therapy being used to treat insomnia disorder: An open label clinical trial pilot study compared with historical controls.
Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone.
Topics: Humans; Modafinil; Pilot Projects; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome; Wakefulness
PubMed: 36003019
DOI: 10.1111/jsr.13699 -
European Journal of Pharmaceutics and... Dec 2021Cognition maintenance is essential for healthy and safe life if sleep deprivation happens. Armodafinil is a wake-promoting agent against sleep deprivation related...
Cognition maintenance is essential for healthy and safe life if sleep deprivation happens. Armodafinil is a wake-promoting agent against sleep deprivation related disorders. However, only the tablet formulation is available, which may limit its potential in some circumstances. Here, we report the synthesis of a new formulation of armodafinil, microneedle patches, which can be conveniently used by any individual and removed in time if not wanted. To produce the needles of higher mechanical strength and higher drug loading, polyvinylpyrrolidone (PVP) K90 was used to fabricate armodafinil-loaded microneedles by applying the mold casting method after dissolving in methanol and drying. The higher mechanical strength was validated by COMSOL Multiphysics® software stimulation and universal mechanical testing machines. The obtained armodafinil microneedles can withstand a force of 70 N and penetrate the skin to a depth of 230 μm, and quickly released the drug within 1.5 h in vitro. The pharmacokinetic analysis showed that microneedle administration can maintain a more lasting and stable blood concentration as compared to oral administration. After the treatment of sleep deprived mice with microneedles, the in vivo pharmacodynamics study clearly demonstrated that armodafinil microneedles could eliminate the effects of sleep deprivation and improve the cognitive functions of sleep-deprived mice. A self-administered, high drug-loaded microneedle patch were prepared successfully, which appeared to be highly promising in preserving cognition by transdermal administration.
Topics: Administration, Cutaneous; Animals; Cognition; Drug Delivery Systems; Drug Monitoring; Mice; Microtechnology; Modafinil; Needles; Pharmaceutic Aids; Povidone; Skin Absorption; Sleep Deprivation; Sleep Wake Disorders; Solubility; Transdermal Patch; Wakefulness-Promoting Agents
PubMed: 34700002
DOI: 10.1016/j.ejpb.2021.10.009 -
The Annals of Pharmacotherapy Oct 2021To describe the efficacy and safety of pharmacologic neurostimulants after neurological injuries such as ischemic or hemorrhagic stroke and traumatic brain injury (TBI),... (Review)
Review
OBJECTIVE
To describe the efficacy and safety of pharmacologic neurostimulants after neurological injuries such as ischemic or hemorrhagic stroke and traumatic brain injury (TBI), critically evaluate the available literature, and make recommendations regarding which neurostimulants should be considered for use in clinical practice.
DATA SOURCES
A literature search of PubMed was performed (1953 to October 2020) to identify relevant articles. Search terms included the following: "neurostimulant, neurorehabilitation" AND "traumatic brain injury, cerebrovascular accident, or stroke." This review is limited to prospective studies and observational trials.
STUDY SELECTION AND DATA EXTRACTION
Relevant English-language studies conducted in humans were considered.
DATA SYNTHESIS
Cognitive and motor deficits caused by stroke and TBI account for high rates of long-term disability. Although not well-established, pharmacologic agents, broadly characterized as neurostimulants, may be prescribed after brain injury to treat these deficits. When prescribing these medications, it is imperative to be aware of the supporting evidence in order to accurately gauge the risk-benefit profile of each agent.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
The following presents a literature review critically evaluating clinical studies that investigate neurostimulant use after brain injury. The intent of this review is to serve as an evidence-based guide for clinicians.
CONCLUSIONS
The pharmacologic agent with the most supporting literature is amantadine used for cognitive improvement after TBI. Other neurostimulants with positive, despite more limited, evidence include methylphenidate, modafinil, levodopa, and citalopram. Caution is warranted with other neurostimulants given higher rates of adverse effects or lack of benefit observed in clinical trials.
Topics: Brain Injuries; Humans; Modafinil; Prospective Studies; Risk Assessment; Stroke
PubMed: 33435717
DOI: 10.1177/1060028020983607 -
JAMA Internal Medicine Feb 2021
Topics: Central Nervous System Stimulants; Female; Humans; Modafinil; Pregnancy; Wakefulness
PubMed: 33074296
DOI: 10.1001/jamainternmed.2020.4206 -
International Journal of Pharmaceutics Mar 2021Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility...
Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility and large dosage limit its effective application. Herein, we formulated armodafinil in a nanocrystal hydrogel (NCsG) with appropriate fluidity and viscosity, capable of rapidly dissolving after staying in the nasal cavity for > 4 h and then penetrating the mucosa as quickly as possible in vitro. We found that armodafinil NCsG was biologically safe, as it had no visible ciliary toxicity, as well as extremely stable due to the existence of intermolecular hydrogen-bonding forces. Nasal administration of armodafinil NCsG proved to be more efficient and targeted than oral administration due to its preferential absorption in plasma and more-concentrated distribution in the brain. In addition, compared with the model group, sleep-deprived rats treated with NCsG undergoing Morris water maze (MWM) behavioral experiments had shorter escape latency and much more shuttle times across the platform. Meanwhile, in the open-field test (OFT), these same rats had longer periods of movement in the center, longer time spent upright, and lower anxiety, which clearly demonstrated improved cognitive awareness and wakefulness after intranasal administration. Moreover, we speculated that armodafinil NCsG had a protective effect on hippocampal neurons in Cortical Area 1 (CA1), which is closely related to cognitive function, by upregulating brain-derived neurotrophic factor (BDNF) protein expression. Consequently, the intranasal administration of armodafinil NCsG could serve as a promising integrated-control measure for sleep deprivation.
Topics: Animals; Benzhydryl Compounds; Cognition; Double-Blind Method; Humans; Hydrogels; Modafinil; Nanoparticles; Rats; Sleep
PubMed: 33545288
DOI: 10.1016/j.ijpharm.2021.120343 -
Psychopharmacology Feb 2021At all times humans have made attempts to improve their cognitive abilities by different means, among others, with the use of stimulants. Widely available stimulants... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONAL
At all times humans have made attempts to improve their cognitive abilities by different means, among others, with the use of stimulants. Widely available stimulants such as caffeine, but also prescription substances such as methylphenidate and modafinil, are being used by healthy individuals to enhance cognitive performance.
OBJECTIVES
There is a lack of knowledge on the effects of prescription stimulants when taken by healthy individuals (as compared with patients) and especially on the effects of different substances across different cognitive domains.
METHODS
We conducted a pilot study with three arms in which male participants received placebo and one of three stimulants (caffeine, methylphenidate, modafinil) and assessed cognitive performance with a test battery that captures various cognitive domains.
RESULTS
Our study showed some moderate effects of the three stimulants tested. Methylphenidate had positive effects on self-reported fatigue as well as on declarative memory 24 hours after learning; caffeine had a positive effect on sustained attention; there was no significant effect of modafinil in any of the instruments of our test battery. All stimulants were well tolerated, and no trade-off negative effects on other cognitive domains were found.
CONCLUSIONS
The few observed significant positive effects of the tested stimulants were domain-specific and of rather low magnitude. The results can inform the use of stimulants for cognitive enhancement purposes as well as direct further research to investigate the effects of stimulants on specific cognitive domains that seem most promising, possibly by using tasks that are more demanding.
Topics: Adult; Attention; Caffeine; Central Nervous System Stimulants; Cognition; Double-Blind Method; Fatigue; Humans; Male; Methylphenidate; Modafinil; Nootropic Agents; Pilot Projects; Treatment Outcome; Young Adult
PubMed: 33201262
DOI: 10.1007/s00213-020-05691-w -
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 -
Respiratory Medicine Mar 2007Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population.
METHODS
In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory.
RESULTS
At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil.
CONCLUSION
Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.
Topics: Adjuvants, Pharmaceutic; Adult; Aged; Attention; Benzhydryl Compounds; Central Nervous System Stimulants; Continuous Positive Airway Pressure; Double-Blind Method; Fatigue; Female; Humans; Male; Memory; Middle Aged; Modafinil; Psychological Tests; Sleep; Sleep Apnea, Obstructive; Time Factors; Treatment Outcome; Wakefulness
PubMed: 16908126
DOI: 10.1016/j.rmed.2006.06.007 -
Brain and Nerve = Shinkei Kenkyu No... May 2023Treatment of narcolepsy is based on the need to regulate life rhythms. Psychostimulants such as modafinil, methylphenidate-immediate release, and pemoline are used to...
Treatment of narcolepsy is based on the need to regulate life rhythms. Psychostimulants such as modafinil, methylphenidate-immediate release, and pemoline are used to treat hypersomnia. A psychosocial approach is considered the mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD), and medication is used to treat moderate or severe ADHD symptoms. Two of the four drugs approved in Japan for ADHD therapy (osmotic-release oral system methylphenidate and lisdexamfetamine dimesylate) are psychostimulants, which are administered via the ADHD proper distribution management system.
Topics: Humans; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate; Attention Deficit Disorder with Hyperactivity; Methylphenidate; Modafinil
PubMed: 37194538
DOI: 10.11477/mf.1416202385 -
Journal of Psychiatric Research Jan 2015We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of modafinil or armodafinil (ar/mod) augmentation in schizophrenia. We searched... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of modafinil or armodafinil (ar/mod) augmentation in schizophrenia. We searched PubMed, clinical trial registries, reference lists, and other sources for parallel group, placebo-controlled RCTs. Our primary outcome variable was the effect of ar/mod on negative symptom outcomes. Eight RCTs (pooled N = 372; median duration, 8 weeks) met our selection criteria. Ar/mod (200 mg/day) significantly attenuated negative symptom ratings (6 RCTs; N = 322; standardized mean difference [SMD], -0.26; 95% CI, -0.48 to -0.04). This finding remained similar in all but one sensitivity analysis - when the only RCT in acutely ill patients was excluded, the outcome was no longer statistically significant (SMD, -0.17; 95% CI, -0.51 to 0.06). The absolute advantage for ar/mod was small: just 0.27 points on the PANSS-N (6 RCTs). Ar/mod attenuated total psychopathology ratings (7 RCTs; N = 342; SMD, -0.23; 95% CI, -0.45 to -0.02) but did not influence positive symptom ratings (5 RCTs; N = 302; mean difference, -0.58; 95% CI, -1.71 to 0.55). Although data were limited, cognition, fatigue, daytime drowsiness, adverse events, and drop out rates did not differ significantly between ar/mod and placebo groups. Fixed and random effects models yielded similar results. There was no heterogeneity in all but one analysis. Publication bias could not be tested. We conclude that ar/mod (200 mg/day) is safe and well tolerated in the short-term treatment of schizophrenia. Ar/mod reduces negative symptoms with a small effect size; the absolute advantage is also small, and the advantage disappears when chronically ill patients or those with high negative symptom burden are treated. Ar/mod does not benefit or worsen other symptom dimensions in schizophrenia.
Topics: Adult; Antipsychotic Agents; Benzhydryl Compounds; Cognition; Fatigue; Female; Humans; Male; Middle Aged; Modafinil; Randomized Controlled Trials as Topic; Schizophrenia; Sleep Stages; Wakefulness-Promoting Agents
PubMed: 25306261
DOI: 10.1016/j.jpsychires.2014.09.013