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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 -
Advances in Pharmacology (San Diego,... 2024Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has...
Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.
Topics: Humans; Modafinil; Central Nervous System Stimulants; Benzhydryl Compounds; Dopamine; Substance-Related Disorders
PubMed: 38467484
DOI: 10.1016/bs.apha.2023.10.006 -
Biomedical Chromatography : BMC Nov 2018Armodafinil is a wake-promoting agent approved in 2007 by the US Food and Drug Administration for the treatment of excessive sleepiness. A rapid, sensitive and selective...
Armodafinil is a wake-promoting agent approved in 2007 by the US Food and Drug Administration for the treatment of excessive sleepiness. A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of armodafinil in human plasma was developed and validated. Armodafinil and internal standard (armodafinil d-10) were extracted from human plasma using protein precipitation combined with liquid-liquid extraction. This developed method only requires 50 μL of plasma for the analysis. The chromatographic separation was performed with a Waters symmetry, C , 4.6 × 150 mm, 5 μm column using formic acid, water and acetonitrile as solvent delivered at a 0.7 mL/min flow rate. The total run time of the method was 3 min. The method was validated according to regulatory guidance in terms of specificity, selectivity, linearity, matrix effect, recovery and stability. Optimized Q1/Q3 mass transitions for armodafinil and armodafinil d-10 were 274.1/167.2 (m/z) and 284.4/177.4 (m/z) respectively. The method showed linearity within the tested concentration range of 10-10,000 ng/mL. The method was successfully applied to quantify armodafinil concentrations after single oral administration of a 250 mg tablet in a clinical study conducted in healthy volunteers. Significant advantages of this method are minimal sample volume, short run time and a lower LLOQ.
Topics: Benzhydryl Compounds; Chromatography, Liquid; Drug Stability; Humans; Linear Models; Modafinil; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 30003558
DOI: 10.1002/bmc.4342 -
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 -
Journal of Clinical Sleep Medicine :... Feb 2014To assess the effect of armodafinil on task-related prefrontal cortex activation using functional magnetic resonance imaging (fMRI) in patients with obstructive sleep... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
To assess the effect of armodafinil on task-related prefrontal cortex activation using functional magnetic resonance imaging (fMRI) in patients with obstructive sleep apnea (OSA) and excessive sleepiness despite continuous positive airway pressure (CPAP) therapy.
METHODS
This 2-week, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study was conducted at five neuroimaging sites and four collaborating clinical study centers in the United States. Patients were 40 right-handed or ambidextrous men and women aged between 18 and 60 years, with OSA and persistent sleepiness, as determined by multiple sleep latency and Epworth Sleepiness Scale scores, despite effective, stable use of CPAP. Treatment was randomized (1:1) to once-daily armodafinil 200 mg or placebo. The primary efficacy outcome was a change from baseline at week 2 in the volume of activation meeting the predefined threshold in the dorsolateral prefrontal cortex during a 2-back working memory task. The key secondary measure was the change in task response latency.
RESULTS
No significant differences were observed between treatment groups in the primary or key secondary outcomes. Armodafinil was generally well tolerated. The most common adverse events (occurring in more than one patient [5%]) were headache (19%), nasopharyngitis (14%), and diarrhea (10%).
CONCLUSIONS
Armodafinil did not improve fMRI-measured functional brain activation in CPAP-treated patients with OSA and excessive sleepiness.
STUDY REGISTRATION
Double-Blind, Placebo-Controlled, Functional Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal Cortical Activation in Patients With Residual Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea.
Topics: Adolescent; Adult; Benzhydryl Compounds; Cerebral Cortex; Continuous Positive Airway Pressure; Disorders of Excessive Somnolence; Double-Blind Method; Female; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term; Middle Aged; Modafinil; Prospective Studies; Sleep Apnea, Obstructive; Treatment Outcome; Wakefulness-Promoting Agents; Young Adult
PubMed: 24532997
DOI: 10.5664/jcsm.3440 -
JAAPA : Official Journal of the... Sep 2009
Topics: Benzhydryl Compounds; Central Nervous System Stimulants; Clinical Trials as Topic; Humans; Modafinil; Sleep Wake Disorders
PubMed: 19827390
DOI: No ID Found -
Journal of the Neurological Sciences Feb 2019
Topics: Headache; Humans; Hypertension; Modafinil; Monoamine Oxidase Inhibitors; Tranylcypromine
PubMed: 30641245
DOI: 10.1016/j.jns.2019.01.002 -
Journal of Clinical Sleep Medicine :... May 2013Obstructive sleep apnea (OSA) has been associated with an increased risk of motor vehicle crashes. This driving risk can be reduced (≥ 50%) by treatment with... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
Obstructive sleep apnea (OSA) has been associated with an increased risk of motor vehicle crashes. This driving risk can be reduced (≥ 50%) by treatment with continuous positive airway pressure (CPAP). However residual excessive daytime sleepiness (EDS) can persist for some patients who regularly use CPAP. The current study was designed to assess the effect of armodafinil on simulated driving performance and subsequent CPAP treatment compliance in newly diagnosed OSA patients with EDS during a 2-week "waiting period" prior to initiation of CPAP.
METHODS
Sixty-nine newly diagnosed OSA patients, awaiting CPAP therapy, were randomized (1:1) to placebo or armodafinil (150 mg/day) treatment. Simulated driving tests and self-report measures were completed at baseline, after 2 weeks of drug treatment, and following 6 weeks of CPAP treatment. CPAP compliance was evaluated at the end of 6 weeks of CPAP.
RESULTS
Compared to placebo, armodafinil improved simulated driving safety performance in OSA patients awaiting CPAP therapy (p = 0.03). Improvement was seen in lane position deviation (p = 0.002) and number of lane excursions (p = 0.02). Improvement was also observed on measures of sleepiness using the Epworth Sleepiness Scale (ESS) and sleep related quality of life. Following 6 weeks of CPAP, there was also significant improvement observed on multiple measures of simulated driving performance. CPAP compliance did not differ between armodafinil-treated and placebo-treated patients (p = 0.80).
CONCLUSIONS
Armodafinil was found to improve simulated driving performance in OSA patients with EDS prior to initiation of CPAP. Treatment with armodafinil showed no effect on subsequent CPAP compliance.
Topics: Adult; Automobile Driving; Benzhydryl Compounds; Computer Simulation; Continuous Positive Airway Pressure; Double-Blind Method; Female; Humans; Male; Modafinil; Patient Compliance; Psychomotor Performance; Self Report; Sleep Apnea, Obstructive; Treatment Outcome; Wakefulness; Wakefulness-Promoting Agents
PubMed: 23674935
DOI: 10.5664/jcsm.2662 -
Clinical Drug Investigation 2009Armodafinil, the R- and longer-lasting isomer of modafinil, may maintain higher plasma drug concentrations compared with racemic modafinil because of stereospecific... (Comparative Study)
Comparative Study
Comparison of steady-state plasma concentrations of armodafinil and modafinil late in the day following morning administration: post hoc analysis of two randomized, double-blind, placebo-controlled, multiple-dose studies in healthy male subjects.
BACKGROUND AND OBJECTIVE
Armodafinil, the R- and longer-lasting isomer of modafinil, may maintain higher plasma drug concentrations compared with racemic modafinil because of stereospecific differences in elimination of its isomers. This analysis set out to compare the steady-state pharmacokinetic profiles of armodafinil and modafinil on a milligram-to-milligram basis following once-daily administration.
METHODS
A post hoc analysis of two multiple-dose pharmacokinetic studies in healthy male subjects aged 18-50 years was conducted to compare dose-normalized (200 mg/day) plasma drug concentration and pharmacokinetic data for subjects in each study who completed 7 days of once-daily (morning) administration of armodafinil (n = 34) or modafinil (n = 18).
RESULTS
Dose-normalized plasma concentrations of armodafinil on day 7 were higher than those of modafinil, with the greatest differences being observed later in the day. Across the 24-hour dose interval, plasma drug concentration fluctuation and swing were 28% and 42% less, respectively, with armodafinil than with modafinil. In addition, average late-day (3 pm to 7 pm after an 8 am dosing) plasma drug concentrations and partial values for the area under the plasma concentration versus time curve for 7-11 hours after dosing were both 44% higher with armodafinil.
CONCLUSIONS
At steady state, armodafinil produces consistently higher plasma drug concentrations late in the day than modafinil when compared on a milligram-to-milligram basis. The distinct pharmacokinetic profile of armodafinil compared with that of the racemate may result in fundamentally different durations of action. These differences between the two medications cannot be made equivalent by increasing the dose of the racemate without introducing potential safety concerns.
Topics: Adolescent; Adult; Benzhydryl Compounds; Central Nervous System Stimulants; Double-Blind Method; Drug Administration Schedule; Humans; Male; Middle Aged; Modafinil; Placebos; Randomized Controlled Trials as Topic; Time Factors
PubMed: 19663522
DOI: 10.2165/11317740-000000000-00000 -
Supportive Care in Cancer : Official... Jun 2015Fatigue is a common problem among multiple myeloma (MM) patients. Armodafinil is a drug known to promote wakefulness, which is related to modafinil, a compound that... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Fatigue is a common problem among multiple myeloma (MM) patients. Armodafinil is a drug known to promote wakefulness, which is related to modafinil, a compound that improves fatigue in some cancer patients treated with chemotherapeutic agents. We investigated whether armodafinil could reduce cancer-related fatigue in MM patients.
METHODS
This double-blind, placebo-controlled phase 3 trial evaluated the efficacy of armodafinil in MM patients with evidence of moderate fatigue. Patients were randomized to one of two arms: treatment-only, with armodafinil given at 150 mg/daily for 56 days, or placebo-first, with placebo given on days 1-28, followed by armodafinil administered at 150 mg daily on days 29-56. Fatigue was measured on days 1 (pre-dose: baseline), 15, 28, 43, and 56 using seven separate assessments, including four patient-reported outcomes of fatigue and related quality of life measures, as well as three objective measures of cognitive function.
RESULTS
Overall toxicities were similar between treatment groups. No significant differences were observed between the placebo-first and the treatment-only arms after 28 days. Treatment with armodafinil for 28 additional days did not produce responses. Both placebo-first and treatment-only patients showed similar significant improvements in three patient-reported measures and one objective task at day 28 compared to baseline. Placebo-first patients improved on eight additional measures (one patient-reported measure, six subscales, and one objective task), suggesting a strong placebo effect in this patient population.
CONCLUSIONS
Evaluation and treatment of cancer-related fatigue continues to be challenging; a clear definition of this symptom and better assessment tools are needed.
Topics: Adult; Aged; Benzhydryl Compounds; Cross-Over Studies; Double-Blind Method; Fatigue; Female; Humans; Male; Middle Aged; Modafinil; Multiple Myeloma; Placebo Effect; Quality of Life; Wakefulness; Wakefulness-Promoting Agents
PubMed: 25370889
DOI: 10.1007/s00520-014-2486-7