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Thomas Roth - One of the best experts on this subject based on the ideXlab platform.
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appropriate therapeutic selection for patients with shift work disorder
Sleep Medicine, 2012Co-Authors: Thomas RothAbstract:Abstract Background Shift work disorder (SWD) is characterized by symptoms of excessive sleepiness during work hours or insomnia during allotted daytime sleep hours, as well as by a disruption of the circadian rhythm. Many shift workers with SWD experience significant social, behavioral, and health problems as a result of this disorder. SWD is associated with a higher risk of occupational and motor vehicle accidents, and thus poses a public health risk. Methods Currently there are both pharmacologic and non-pharmacologic treatments for this disorder that can be used to normalize the disruption of the circadian cycle or alleviate the symptoms of excessive sleepiness or insomnia. The American Academy of Sleep Medicine and the British Society of Psychopharmacology have developed guidelines for the diagnosis and treatment of patients with SWD. Results Recommended therapies for altering the circadian cycle include chronobiotics such as melatonin or melatonin agonists and non-pharmacologic interventions such as timed light exposure. Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, Armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness. Conclusions While no therapies (pharmacological or nonpharmacological) can restore altered circadian cycles to baseline levels, proper identification and management of SWD will likely reduce its co-morbidities and improve the quality of life for individuals with this disorder.
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a phase 3 double blind randomized placebo controlled study of Armodafinil for excessive sleepiness associated with jet lag disorder
Mayo Clinic proceedings, 2010Co-Authors: Russell Rosenberg, Ronghua Yang, James M Youakim, Jane M Tiller, Richard K Bogan, Craig Q Earl, Thomas RothAbstract:OBJECTIVE To assess the effect of Armodafinil, the longer-lasting isomer of modafinil, on jet lag disorder. PARTICIPANTS AND METHODS This double-blind, randomized, parallel-group, multicenter study was conducted between September 18, 2008, and February 9, 2009. Adults with a history of jet lag symptoms on previous flights through multiple time zones flew from the United States to France (a 6-hour time zone change) for a 3-day laboratory-based study period. Participants received Armodafinil (50 or 150 mg/d) or placebo each morning. Wakefulness was assessed by the coprimary outcomes, mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of all MSLT sessions across days 1 and 2) and Patient Global Impression of Severity in relation to jet lag symptoms (averaged across days 1 and 2). RESULTS A total of 427 participants received Armodafinil at 50 mg/d (n=142), Armodafinil at 150 mg/d (n=143), or placebo (n=142). Armodafinil at 150 mg/d provided a significant benefit in sleep latency on the MSLT (days 1-2: mean, 11.7 minutes vs 4.8 minutes for placebo; P P CONCLUSION Armodafinil increased wakefulness after eastward travel through 6 time zones. Trial Registration: clinicaltrials.gov identifier: NCT00758498
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Armodafinil in the treatment of sleep/wake disorders
Dove Medical Press, 2010Co-Authors: Jonathan Rl Schwartz, Thomas Roth, Chris DrakeAbstract:Jonathan RL Schwartz1,Thomas Roth2, Chris Drake21INTEGRIS Sleep Disorders Center and University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USAAbstract: Excessive sleepiness (ES) is a major but underestimated public health concern associated with significant impairments in alertness/wakefulness and significant morbidity. The term ES has been used in the sleep medicine literature for years, but due to its nonspecific symptoms (ie tiredness or fatigue), it frequently goes unrecognized or is misdiagnosed in primary care. In some cases ES arises due to poor sleep habits or self-imposed sleep deprivation; however, ES is also a key component of a number of sleep/wake disorders and multiple medical and psychiatric disorders. Identification and treatment of ES is critical to improve the quality of life and well-being of patients and for the safety of the wider community. The inability of patients to recognize the nature, extent, and symptomatic profile of sleep/wake disorders requires vigilance on the part of healthcare professionals. Interventions to address ES and its associated impairments, treatment of the underlying sleep/wake disorder, and follow-up are a priority given the potential for serious consequences if left untreated. Wakefulness-promoting agents are available that treat ES associated with sleep/wake disorders. This review examines current approaches for managing this debilitating and potentially life-threatening condition, focusing on the place of Armodafinil as a wakefulness-promoting agent.Keywords: excessive sleepiness, wakefulness, Armodafinil, obstructive sleep apnea, narcolepsy, shift-work disorde
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Armodafinil for treatment of excessive sleepiness associated with shift work disorder a randomized controlled study
Mayo Clinic Proceedings, 2009Co-Authors: Charles A Czeisler, Keith Wesnes, Sanjay Arora, James K Walsh, Thomas RothAbstract:OBJECTIVE To assess the effect of Armodafinil, 150 mg, on the physiologic propensity for sleep and cognitive performance during usual night shift hours in patients with excessive sleepiness associated with chronic (≥3 months) shift work disorder (SWD) of moderate or greater severity. PATIENTS AND METHODS This 12-week, randomized controlled study was conducted at 42 sleep research facilities in North America from April 2 through December 23, 2004, and enrolled 254 permanent or rotating night shift workers with SWD. Entry criteria included excessive sleepiness during usual night shifts for 3 months or longer (corroborated by mean sleep latency of ≤6 minutes on a Multiple Sleep Latency Test), insomnia (sleep efficiency ≤87.5% during daytime sleep), and SWD that was judged clinically to be of moderate or greater severity. Patients received Armodafinil, 150 mg, or placebo 30 to 60 minutes before each night shift. Physiologic sleep propensity during night shift hours, clinical impression of severity, patient-reported sleepiness, and cognitive function were assessed during laboratory night shifts at weeks 4, 8, and 12. RESULTS Armodafinil significantly improved mean (SD) sleep latency from 2.3 (1.6) minutes at baseline to 5.3 (5.0) minutes at final visit, compared with a change from 2.4 (1.6) minutes to 2.8 (2.9) minutes in the placebo group ( P P =.001). As reported by patients' diaries, Armodafinil significantly reduced sleepiness during laboratory nights ( P P P =.003). Armodafinil improved performance on standardized memory ( P P =.001; continuity, P CONCLUSION In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, Armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention. Trial Registration: clinicaltrials.gov Identifier: NCT00080288
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adjunct Armodafinil improves wakefulness and memory in obstructive sleep apnea hypopnea syndrome
Respiratory Medicine, 2007Co-Authors: Max Hirshkowitz, Sanjay Arora, Gwendolyn E Niebler, Jed Black, Keith Wesnes, Thomas RothAbstract:Summary 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 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.
Jed Black - One of the best experts on this subject based on the ideXlab platform.
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adjunct Armodafinil improves wakefulness and memory in obstructive sleep apnea hypopnea syndrome
Respiratory Medicine, 2007Co-Authors: Max Hirshkowitz, Sanjay Arora, Gwendolyn E Niebler, Jed Black, Keith Wesnes, Thomas RothAbstract:Summary 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 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.
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adjunct Armodafinil improves wakefulness and memory in obstructive sleep apnea hypopnea syndrome
Respiratory Medicine, 2007Co-Authors: Max Hirshkowitz, Sanjay Arora, Gwendolyn E Niebler, Jed Black, Keith Wesnes, Thomas RothAbstract:Summary 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 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.
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effects of Armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea hypopnea syndrome a 12 week multicenter double blind randomized placebo controlled study in ncpap adherent adults
Clinical Therapeutics, 2006Co-Authors: Thomas Roth, Sanjay Arora, Gwendolyn E Niebler, Keith Wesnes, David P White, Wolfgang Schmidtnowara, Jed BlackAbstract:Background: Some patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) experience excessive sleepiness (ES) that might not resolve with nasal continuous positive airway pressure (nCPAP) treatment. Objective: The aim of the present study was to assess the efficacy and tolerability of Armodafinil 150 or 250 mg QD when used as adjunctive treatment for residual ES associated with OSA/HS in patients who are adherent to nCPAP therapy. Methods: This 12-week, multicenter, double-blind, randomized, placebo-controlled study was conducted at 37 centers in the United States and Canada. Male and female patients aged 18 to 65 years with residual ES associated with OSA/HS were enrolled. Patients were randomly assigned to receive Armodafinil 150 or 250 mg or placebo PO QD for 12 weeks. Assessments were conducted at baseline and study weeks 4, 8, and 12 and included the Maintenance of Wakefulness Test (MWT) to determine wakefulness, the Clinical Global Impression of Change (CGI-C) to determine improvement in clinical condition, the Epworth Sleepiness Scale (ESS) to determine patient-estimated wakefulness, the Brief Fatigue Inventory (BFI) to determine global fatigue, and the Cognitive Drug Research computerized assessment battery. To distinguish between earlier and later effects, sleep latencies, assessed using the MWT, were averaged across the first 4 (9 and 11 AM, and 1 and 3 PM) and last 3 (3, 5, and 7 PM) tests. Tolerability assessments included monitoring of adverse events (AEs), clinical laboratory tests, vital sign measurements, and electrocardiography. Results: A total of 395 patients were enrolled in the study (Armodafinil 150 mg/d, 133; Armodafinil 250 mg/d, 131; placebo, 131); 392 received ≥1 dose of study drug (Armodafinil 150 mg/d, 131; Armodafinil 250 mg/d, 131; placebo, 130). The Armodafinil and placebo groups were well matched with regard to age (mean [SD], 49.2 [8.9] vs 50.1 [9.4] years), sex (71 vs 69% men), race (84% vs 87% white), and body weight (mean [SD], 110.3 [24.9] vs 111.9 [24.0] kg). At the final visit, the mean (SD) change from baseline in MWT sleep latency across the morning and afternoon was significantly greater in the Armodafinil combined group compared with the placebo group (+1.9 [7.3] vs 1.7 [8.6] minutes; P < 0.001). Also at the final visit, the proportions of patients who showed at least minimal improvement on the CGI-C, and the mean (SD) changes from baseline in ESS and BFI scores, were significantly greater in the Armodafinil group compared with those in the placebo group (72% vs 37%, −5.5 [5.0] vs −3.3 [4.7], and −1.2 [2.2] vs −0.6 [2.0], respectively; P < 0.001, P < 0.001, and P < 0.01, respectively). No significant effects on nighttime sleep, as assessed using polysomnography, were found with Armodafinil. AEs reported in the Armodafinil combined and placebo groups were headache, nausea, insomnia, anxiety, and dizziness. Serious AEs (ulcerative colitis, migraine, worsening of Axis II and mood disorder, and duodenal ulcer) were reported in 4 (1.5%) patients receiving Armodafinil and were considered by the investigator not or unlikely to be drug related. Conclusions: In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, Armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition. Clinical benefit was shown at the first assessment and maintained for the 12-week duration of the study. Armodafinil was also associated with significantly reduced interference of ES with daily activities and global fatigue. Armodafinil was well tolerated, with no adverse effect on nighttime sleep or nCPAP use.
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effects of Armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea hypopnea syndrome a 12 week multicenter double blind randomized placebo controlled study in ncpap adherent adults
Clinical Therapeutics, 2006Co-Authors: Thomas Roth, Sanjay Arora, Gwendolyn E Niebler, Keith Wesnes, David P White, Wolfgang Schmidtnowara, Jed BlackAbstract:Background: Some patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) experience excessive sleepiness (ES) that might not resolve with nasal continuous positive airway pressure (nCPAP) treatment. Objective: The aim of the present study was to assess the efficacy and tolerability of Armodafinil 150 or 250 mg QD when used as adjunctive treatment for residual ES associated with OSA/HS in patients who are adherent to nCPAP therapy. Methods: This 12-week, multicenter, double-blind, randomized, placebo-controlled study was conducted at 37 centers in the United States and Canada. Male and female patients aged 18 to 65 years with residual ES associated with OSA/HS were enrolled. Patients were randomly assigned to receive Armodafinil 150 or 250 mg or placebo PO QD for 12 weeks. Assessments were conducted at baseline and study weeks 4, 8, and 12 and included the Maintenance of Wakefulness Test (MWT) to determine wakefulness, the Clinical Global Impression of Change (CGI-C) to determine improvement in clinical condition, the Epworth Sleepiness Scale (ESS) to determine patient-estimated wakefulness, the Brief Fatigue Inventory (BFI) to determine global fatigue, and the Cognitive Drug Research computerized assessment battery. To distinguish between earlier and later effects, sleep latencies, assessed using the MWT, were averaged across the first 4 (9 and 11 AM, and 1 and 3 PM) and last 3 (3, 5, and 7 PM) tests. Tolerability assessments included monitoring of adverse events (AEs), clinical laboratory tests, vital sign measurements, and electrocardiography. Results: A total of 395 patients were enrolled in the study (Armodafinil 150 mg/d, 133; Armodafinil 250 mg/d, 131; placebo, 131); 392 received ≥1 dose of study drug (Armodafinil 150 mg/d, 131; Armodafinil 250 mg/d, 131; placebo, 130). The Armodafinil and placebo groups were well matched with regard to age (mean [SD], 49.2 [8.9] vs 50.1 [9.4] years), sex (71 vs 69% men), race (84% vs 87% white), and body weight (mean [SD], 110.3 [24.9] vs 111.9 [24.0] kg). At the final visit, the mean (SD) change from baseline in MWT sleep latency across the morning and afternoon was significantly greater in the Armodafinil combined group compared with the placebo group (+1.9 [7.3] vs 1.7 [8.6] minutes; P < 0.001). Also at the final visit, the proportions of patients who showed at least minimal improvement on the CGI-C, and the mean (SD) changes from baseline in ESS and BFI scores, were significantly greater in the Armodafinil group compared with those in the placebo group (72% vs 37%, −5.5 [5.0] vs −3.3 [4.7], and −1.2 [2.2] vs −0.6 [2.0], respectively; P < 0.001, P < 0.001, and P < 0.01, respectively). No significant effects on nighttime sleep, as assessed using polysomnography, were found with Armodafinil. AEs reported in the Armodafinil combined and placebo groups were headache, nausea, insomnia, anxiety, and dizziness. Serious AEs (ulcerative colitis, migraine, worsening of Axis II and mood disorder, and duodenal ulcer) were reported in 4 (1.5%) patients receiving Armodafinil and were considered by the investigator not or unlikely to be drug related. Conclusions: In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, Armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition. Clinical benefit was shown at the first assessment and maintained for the 12-week duration of the study. Armodafinil was also associated with significantly reduced interference of ES with daily activities and global fatigue. Armodafinil was well tolerated, with no adverse effect on nighttime sleep or nCPAP use.
Sanjay Arora - One of the best experts on this subject based on the ideXlab platform.
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Armodafinil for treatment of excessive sleepiness associated with shift work disorder a randomized controlled study
Mayo Clinic Proceedings, 2009Co-Authors: Charles A Czeisler, Keith Wesnes, Sanjay Arora, James K Walsh, Thomas RothAbstract:OBJECTIVE To assess the effect of Armodafinil, 150 mg, on the physiologic propensity for sleep and cognitive performance during usual night shift hours in patients with excessive sleepiness associated with chronic (≥3 months) shift work disorder (SWD) of moderate or greater severity. PATIENTS AND METHODS This 12-week, randomized controlled study was conducted at 42 sleep research facilities in North America from April 2 through December 23, 2004, and enrolled 254 permanent or rotating night shift workers with SWD. Entry criteria included excessive sleepiness during usual night shifts for 3 months or longer (corroborated by mean sleep latency of ≤6 minutes on a Multiple Sleep Latency Test), insomnia (sleep efficiency ≤87.5% during daytime sleep), and SWD that was judged clinically to be of moderate or greater severity. Patients received Armodafinil, 150 mg, or placebo 30 to 60 minutes before each night shift. Physiologic sleep propensity during night shift hours, clinical impression of severity, patient-reported sleepiness, and cognitive function were assessed during laboratory night shifts at weeks 4, 8, and 12. RESULTS Armodafinil significantly improved mean (SD) sleep latency from 2.3 (1.6) minutes at baseline to 5.3 (5.0) minutes at final visit, compared with a change from 2.4 (1.6) minutes to 2.8 (2.9) minutes in the placebo group ( P P =.001). As reported by patients' diaries, Armodafinil significantly reduced sleepiness during laboratory nights ( P P P =.003). Armodafinil improved performance on standardized memory ( P P =.001; continuity, P CONCLUSION In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, Armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention. Trial Registration: clinicaltrials.gov Identifier: NCT00080288
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adjunct Armodafinil improves wakefulness and memory in obstructive sleep apnea hypopnea syndrome
Respiratory Medicine, 2007Co-Authors: Max Hirshkowitz, Sanjay Arora, Gwendolyn E Niebler, Jed Black, Keith Wesnes, Thomas RothAbstract:Summary 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 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.
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adjunct Armodafinil improves wakefulness and memory in obstructive sleep apnea hypopnea syndrome
Respiratory Medicine, 2007Co-Authors: Max Hirshkowitz, Sanjay Arora, Gwendolyn E Niebler, Jed Black, Keith Wesnes, Thomas RothAbstract:Summary 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 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.
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battery, Epworth Sleepiness Scale, and Brief Fatigue
2007Co-Authors: Thomas Roth, Sanjay Arora, T. RothAbstract:Armodafinil improves wakefulness and long-term episodic memory in nCPAP-adherent patients with excessive sleepiness associated with obstructive sleep apne
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effects of Armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea hypopnea syndrome a 12 week multicenter double blind randomized placebo controlled study in ncpap adherent adults
Clinical Therapeutics, 2006Co-Authors: Thomas Roth, Sanjay Arora, Gwendolyn E Niebler, Keith Wesnes, David P White, Wolfgang Schmidtnowara, Jed BlackAbstract:Background: Some patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) experience excessive sleepiness (ES) that might not resolve with nasal continuous positive airway pressure (nCPAP) treatment. Objective: The aim of the present study was to assess the efficacy and tolerability of Armodafinil 150 or 250 mg QD when used as adjunctive treatment for residual ES associated with OSA/HS in patients who are adherent to nCPAP therapy. Methods: This 12-week, multicenter, double-blind, randomized, placebo-controlled study was conducted at 37 centers in the United States and Canada. Male and female patients aged 18 to 65 years with residual ES associated with OSA/HS were enrolled. Patients were randomly assigned to receive Armodafinil 150 or 250 mg or placebo PO QD for 12 weeks. Assessments were conducted at baseline and study weeks 4, 8, and 12 and included the Maintenance of Wakefulness Test (MWT) to determine wakefulness, the Clinical Global Impression of Change (CGI-C) to determine improvement in clinical condition, the Epworth Sleepiness Scale (ESS) to determine patient-estimated wakefulness, the Brief Fatigue Inventory (BFI) to determine global fatigue, and the Cognitive Drug Research computerized assessment battery. To distinguish between earlier and later effects, sleep latencies, assessed using the MWT, were averaged across the first 4 (9 and 11 AM, and 1 and 3 PM) and last 3 (3, 5, and 7 PM) tests. Tolerability assessments included monitoring of adverse events (AEs), clinical laboratory tests, vital sign measurements, and electrocardiography. Results: A total of 395 patients were enrolled in the study (Armodafinil 150 mg/d, 133; Armodafinil 250 mg/d, 131; placebo, 131); 392 received ≥1 dose of study drug (Armodafinil 150 mg/d, 131; Armodafinil 250 mg/d, 131; placebo, 130). The Armodafinil and placebo groups were well matched with regard to age (mean [SD], 49.2 [8.9] vs 50.1 [9.4] years), sex (71 vs 69% men), race (84% vs 87% white), and body weight (mean [SD], 110.3 [24.9] vs 111.9 [24.0] kg). At the final visit, the mean (SD) change from baseline in MWT sleep latency across the morning and afternoon was significantly greater in the Armodafinil combined group compared with the placebo group (+1.9 [7.3] vs 1.7 [8.6] minutes; P < 0.001). Also at the final visit, the proportions of patients who showed at least minimal improvement on the CGI-C, and the mean (SD) changes from baseline in ESS and BFI scores, were significantly greater in the Armodafinil group compared with those in the placebo group (72% vs 37%, −5.5 [5.0] vs −3.3 [4.7], and −1.2 [2.2] vs −0.6 [2.0], respectively; P < 0.001, P < 0.001, and P < 0.01, respectively). No significant effects on nighttime sleep, as assessed using polysomnography, were found with Armodafinil. AEs reported in the Armodafinil combined and placebo groups were headache, nausea, insomnia, anxiety, and dizziness. Serious AEs (ulcerative colitis, migraine, worsening of Axis II and mood disorder, and duodenal ulcer) were reported in 4 (1.5%) patients receiving Armodafinil and were considered by the investigator not or unlikely to be drug related. Conclusions: In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, Armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition. Clinical benefit was shown at the first assessment and maintained for the 12-week duration of the study. Armodafinil was also associated with significantly reduced interference of ES with daily activities and global fatigue. Armodafinil was well tolerated, with no adverse effect on nighttime sleep or nCPAP use.
Patrick M Fuller - One of the best experts on this subject based on the ideXlab platform.
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activation of the gabaergic parafacial zone maintains sleep and counteracts the wake promoting action of the psychostimulants Armodafinil and caffeine
Neuropsychopharmacology, 2018Co-Authors: Kobi Griffith, Christelle Anaclet, Patrick M FullerAbstract:Activation of the GABAergic Parafacial Zone Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants Armodafinil and Caffeine
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Activation of the GABAergic Parafacial Zone Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants Armodafinil and Caffeine
Neuropsychopharmacology, 2018Co-Authors: Christelle Anaclet, Kobi Griffith, Patrick M FullerAbstract:We previously reported that acute and selective activation of GABA-releasing parafacial zone (PZ^Vgat) neurons in behaving mice produces slow-wave-sleep (SWS), even in the absence of sleep deficit, suggesting that these neurons may represent, at least in part, a key cellular substrate underlying sleep drive. It remains, however, to be determined if PZ^Vgat neurons actively maintain, as oppose to simply gate, SWS. To begin to experimentally address this knowledge gap, we asked whether activation of PZ^Vgat neurons could attenuate or block the wake-promoting effects of two widely used wake-promoting psychostimulants, Armodafinil or caffeine. We found that activation of PZ^Vgat neurons completely blocked the behavioral and electrocortical wake-promoting action of Armodafinil. In some contrast, activation of PZ^Vgat neurons inhibited the behavioral, but not electrocortical, arousal response to caffeine. These results suggest that: (1) PZ^Vgat neurons actively maintain, as oppose to simply gate, SWS and cortical slow-wave-activity; (2) Armodafinil cannot exert its wake-promoting effects when PZ^Vgat neurons are activated, intimating a possible shared circuit/molecular basis for mechanism of action; (3) caffeine can continue to exert potent cortical desynchronizing, but not behavioral, effects when PZ^Vgat neurons are activated, inferring a shared and divergent circuit/molecular basis for mechanism of action; and 4) PZ^Vgat neurons represent a key cell population for SWS induction and maintenance.
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2016Co-Authors: Citable Link, Patrick M Fuller, Correspondence Patrick, M FullerAbstract:Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions (Article begins on next page) The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters. Citation Vetrivelan, Ramalingam, Clifford B Saper, and Patrick M Fuller.2014. “Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions. ” Nature and Science of Sleep 6 (1): 57-63. doi:10.2147/NSS.S53132
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activation of the gabaergic parafacial zone maintains sleep and counteracts the wake promoting action of the psychostimulants Armodafinil and caffeine
Neuropsychopharmacology, 2018Co-Authors: Kobi Griffith, Christelle Anaclet, Patrick M FullerAbstract:Activation of the GABAergic Parafacial Zone Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants Armodafinil and Caffeine
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Activation of the GABAergic Parafacial Zone Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants Armodafinil and Caffeine
Neuropsychopharmacology, 2018Co-Authors: Christelle Anaclet, Kobi Griffith, Patrick M FullerAbstract:We previously reported that acute and selective activation of GABA-releasing parafacial zone (PZ^Vgat) neurons in behaving mice produces slow-wave-sleep (SWS), even in the absence of sleep deficit, suggesting that these neurons may represent, at least in part, a key cellular substrate underlying sleep drive. It remains, however, to be determined if PZ^Vgat neurons actively maintain, as oppose to simply gate, SWS. To begin to experimentally address this knowledge gap, we asked whether activation of PZ^Vgat neurons could attenuate or block the wake-promoting effects of two widely used wake-promoting psychostimulants, Armodafinil or caffeine. We found that activation of PZ^Vgat neurons completely blocked the behavioral and electrocortical wake-promoting action of Armodafinil. In some contrast, activation of PZ^Vgat neurons inhibited the behavioral, but not electrocortical, arousal response to caffeine. These results suggest that: (1) PZ^Vgat neurons actively maintain, as oppose to simply gate, SWS and cortical slow-wave-activity; (2) Armodafinil cannot exert its wake-promoting effects when PZ^Vgat neurons are activated, intimating a possible shared circuit/molecular basis for mechanism of action; (3) caffeine can continue to exert potent cortical desynchronizing, but not behavioral, effects when PZ^Vgat neurons are activated, inferring a shared and divergent circuit/molecular basis for mechanism of action; and 4) PZ^Vgat neurons represent a key cell population for SWS induction and maintenance.