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Jed Black - One of the best experts on this subject based on the ideXlab platform.
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impact of sodium oxybate Modafinil and combination treatment on excessive daytime sleepiness in patients who have narcolepsy with or without cataplexy
Sleep Medicine, 2016Co-Authors: Jed Black, Todd J Swick, Richard K Bogan, Lawrence P CarterAbstract:Abstract Background Effects of sodium oxybate (SXB) on patients with narcolepsy with cataplexy (NC) or without cataplexy (NWOC) have not been separately evaluated in clinical trials. Methods Retrospective analysis evaluated data from a phase 3, randomized, placebo-controlled trial of SXB, Modafinil, and SXB + Modafinil versus placebo in adult NC patients ( n = 95) or NWOC patients ( n = 127). NC patients were identified based on medical history, concomitant medications, and sleep-onset REM periods on nocturnal polysomnography. The studied outcomes were changes from baseline at eight weeks on the Epworth Sleepiness Scale (ESS), the Maintenance of Wakefulness Test (MWT), and the Clinical Global Impression of Change (CGI-C). Results Among NC and NWOC patients, ESS improvement was significantly greater with SXB and SXB + Modafinil versus placebo. In NC patients, mean MWT sleep latency was significantly increased with SXB + Modafinil versus placebo. In NWOC patients, mean MWT sleep latency significantly increased in all groups versus placebo. Higher percentages of patients in the SXB and SXB + Modafinil groups were "very much improved" or "much improved" on the CGI-C versus placebo in both NC and NWOC populations, although the difference did not reach statistical significance in the NWOC populations. Adverse events were consistent with previously-reported profiles for Modafinil and SXB. Nausea was more common in the SXB and SXB + Modafinil groups. Dizziness and tremor were more common in the SXB + Modafinil group only. Conclusions SXB alone and in combination with Modafinil improved subjective ratings of excessive sleepiness and an objective measure of the ability to stay awake to similar extents in NC patients and NWOC patients.
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sodium oxybate improves excessive daytime sleepiness in narcolepsy
Sleep, 2006Co-Authors: Jed Black, William C HoughtonAbstract:STUDY OBJECTIVES: To assess the effectiveness of sodium oxybate therapy, Modafinil therapy and the combination of the two for excessive daytime sleepiness in narcolepsy patients previously taking Modafinil. DESIGN: Double-blind, placebo-controlled, multicenter study. SETTING: Forty-four sites in the United States, Canada, the Czech Republic, France, Germany, the Netherlands, Switzerland, and the United Kingdom. PARTICIPANTS: Two hundred seventy- adult patients with narcolepsy taking 200 to 600 mg of Modafinil daily for the treatment of excessive daytime sleepiness. INTERVENTIONS: Patients received unchanged doses of Modafinil (with sodium-oxybate placebo) during a 2-week baseline phase. Following a baseline polysomnogram and Maintenance of Wakefulness Test, they were randomly assigned to 1 of 4 treatment groups: sodium-oxybate placebo plus Modafinil placebo, sodium oxybate plus Modafinil placebo, Modafinil plus sodium-oxybate placebo, or sodium oxybate plus Modafinil. Sodium oxybate was administered as 6 g nightly for 4 weeks and was then increased to 9 g nightly for 4 additional weeks. The primary efficacy measure was the Maintenance of Wakefulness Test; secondary measures included the Epworth Sleepiness Scale, diary recordings, and the Clinical Global Impression-change scale. RESULTS: Following the switch from Modafinil to placebo, the mean average daytime sleep latency on the Maintenance of Wakefulness Test decreased from 9.74 minutes at baseline to 6.87 minutes after 8 weeks (p < .001). In the sodium-oxybate group, there was no decrease in sleep latency, suggesting that this drug was as efficacious in treating the excessive daytime sleepiness as the previously administered Modafinil. In contrast, the sodium-oxybate/Modafinil group demonstrated an increase in daytime sleep latency from 10.43 minutes to 13.15 minutes (p < .001), suggesting that this combination of drugs produced an additive effect. The sodium-oxybate group also demonstrated a decrease in median average Epworth Sleepiness Scale scores, from 15 to 12.0, whereas the sodium-oxybate/Modafinil group decreased from 15.0 to 11.0 (for both, p < .001). The Clinical Global Impression-Change scale demonstrated similar results. CONCLUSIONS: Sodium oxybate and Modafinil are both effective for treating excessive daytime sleepiness in narcolepsy, producing additive effects when used together. Sodium oxybate is beneficial as both monotherapy and as adjunctive therapy for the treatment of excessive daytime sleepiness in narcolepsy.
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Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure treated obstructive sleep apnea hypopnea syndrome
Sleep, 2005Co-Authors: Jed Black, Max HirshkowitzAbstract:STUDY OBJECTIVES: Nasal continuous positive airway pressure (nCPAP) usually reduces sleepiness in patients with obstructive sleep apnea/hypopnea syndrome. However, even with regular use of nCPAP, some patients experience residual excessive sleepiness. We evaluated the efficacy and safety of the wake-promoting agent Modafinil for treating residual excessive sleepiness in nCPAP-treated patients. DESIGN: 12-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. PATIENTS: Patients aged 18 to 70 years diagnosed with obstructive sleep apnea/hypopnea syndrome and having residual excessive sleepiness during nCPAP therapy were eligible. INTERVENTIONS: Once-daily Modafinil, 200 mg or 400 mg, or placebo. MEASUREMENTS AND RESULTS: Assessments included the Maintenance of Wakefulness Test, Epworth Sleepiness Scale, Clinical Global Impression of Change, and Functional Outcomes of Sleep Questionnaire. Both doses of Modafinil significantly improved mean (SD) sleep latency on the Maintenance of Wakefulness Test at weeks 4, 8, and 12 compared with placebo (week 12: Modafinil 400 mg, 15.0 [5.3] minutes; 200 mg, 14.8 [5.3] minutes; placebo, 12.6 [5.8] minutes; P < .0001). The Epworth Sleepiness Scale score decreased more in patients taking Modafinil compared with those in the placebo group (week 12: Modafinil 400 mg, -4.5 [4.3]; 200 mg, -4.5 [4.7]; placebo, -1.8 [3.5]; P < .0001). At week 12, overall clinical condition improved for 61% and 68% of patients treated with Modafinil 200 mg and 400 mg, respectively, versus 37% of placebo-treated patients (P < .001). Modafinil was generally well tolerated and did not adversely affect nighttime sleep or nCPAP use. CONCLUSIONS: These results confirm previous shorter-term controlled trials, indicating Modafinil is a useful adjunct therapy for improving wakefulness in patients with residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome who were treated with nCPAP.
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Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea
American Journal of Respiratory and Critical Care Medicine, 2001Co-Authors: Allan I. Pack, Jonathan R L Schwartz, Jed Black, Jean K MathesonAbstract:Patients with obstructive sleep apnea/hypopnea syndrome can experience residual daytime sleepiness despite regular use of nasal continuous positive airway pressure therapy. This randomized, double-blind, placebo-controlled, parallel group study assessed the efficacy and safety of Modafinil for the treatment of residual daytime sleepiness in such patients. Patients received Modafinil (n = 77) (200 mg/d, Week 1; 400 mg/d, Weeks 2 to 4) or matching placebo (n = 80) once daily for 4 wk. Modafinil significantly improved daytime sleepiness, with significantly greater mean changes from baseline in Epworth Sleepiness Scale scores at Weeks 1 and 4 (p 10 min; 29% versus 25%). Headache (Modafinil, 23%; placebo, 11%; p = 0.044) and nervousness (Modafinil, 12%; p...
Barbara J Sahakian - One of the best experts on this subject based on the ideXlab platform.
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Effects of Modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers
Neuropharmacology, 2013Co-Authors: Ulrike Muller, Timothy Rittman, C Lewis, J B Rowe, Trevor W Robbins, Barbara J SahakianAbstract:Background: Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. The aim of this study was to investigate the effects of Modafinil on non-verbal cognitive functions in healthy volunteers, with a particular focus on variations of cognitive load, measures of motivational factors and the effects on creative problem-solving. Methods: A double-blind placebo-controlled parallel design study evaluated the effect of 200 mg of Modafinil (N = 32) or placebo (N = 32) in non-sleep deprived healthy volunteers. Non-verbal tests of divergent and convergent thinking were used to measure creativity. A new measure of task motivation was used, together with more levels of difficulty on neuropsychological tests from the CANTAB battery. Results: Improvements under Modafinil were seen on spatial working memory, planning and decision making at the most difficult levels, as well as visual pattern recognition memory following delay. Subjective ratings of enjoyment of task performance were significantly greater under Modafinil compared with placebo, but mood ratings overall were not affected. The effects of Modafinil on creativity were inconsistent and did not reach statistical significance. Conclusions: Modafinil reliably enhanced task enjoyment and performance on several cognitive tests of planning and working memory, but did not improve paired associates learning. The findings confirm that Modafinil can enhance aspects of highly demanding cognitive performance in non-sleep deprived individuals. This article is part of a Special Issue entitled 'Cognitive Enhancers'. © 2012 Elsevier Ltd. All rights reserved.
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Modafinil effects on cognition and emotion in schizophrenia and its neurochemical modulation in the brain
Neuropharmacology, 2013Co-Authors: Linda Scoriels, Peter B Jones, Barbara J SahakianAbstract:Abstract Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping. Its vigilance promoting properties and low abuse potential has intrigued the scientific community and has led to use it as a cognitive enhancer, before its neural functions were understood. Here, we review the effects of Modafinil in human cognition and emotion and its specific actions on symptoms in patients with schizophrenia and whether these are consistently effective throughout the literature. We also performed a systematic review on the effects of Modafinil on neurotransmitter signalling in different areas of the brain in order to better understand the neuromechanisms of its cognitive and emotional enhancing properties. A review of its effects in schizophrenia suggests that Modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements. Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies. The systematic review on the neurochemical modulation of the Modafinil suggests that its mnemonic enhancing properties might be the result of glutamatergic and dopaminergic increased neuronal activation in the hippocampus and in the prefrontal cortex respectively. Other neurotransmitters were also activated by Modafinil in various limbic brain areas, suggesting that the drug acts on these brain regions to influence emotional responses. These reviews seek to delineate the neuronal mechanisms by which Modafinil affects cognitive and emotional function. This article is part of a Special Issue entitled ‘Cognitive Enhancers’.
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effects of Modafinil and prazosin on cognitive and physiological functions in healthy volunteers
Journal of Psychopharmacology, 2010Co-Authors: Sophie Winderrhodes, Barbara J Sahakian, Trevor W Robbins, Samuel R Chamberlain, M I Idris, Ulrich MullerAbstract:Previous research has demonstrated cognitive-enhancing effects of Modafinil in humans and generated evidence for its therapeutic potential in psychiatric disorders. The neurochemical basis of these effects remains unresolved although a role for α1-adrenoceptors has been hypothesised. In this within-subject, double-blind, placebo-controlled study, 12 healthy male adults received Modafinil (300 mg), the α1-adrenoceptor antagonist prazosin (3 mg), both together and placebo on separate occasions at least 5 days apart. Cognitive effects were assessed using a well-validated testing battery focusing on executive and working memory functions. Blood pressure, heart rate and salivary α-amylase (sAA) were measured at hourly intervals. Cognitive effects of Modafinil and prazosin were identified at the difficult levels of the One-Touch Stockings of Cambridge (OTSOC) planning task. Prazosin antagonized the error-reducing effect of Modafinil when the agents were given together. In contrast, the combined agents acted synergistically to increase time taken to complete OTSOC problems compared with placebo. The tachycardic and sAA-elevating effects of prazosin were also potentiated by concurrent Modafinil administration. The current data suggest that the cognitive effects of Modafinil on performance accuracy and latency are dissociable in terms of their neurochemical mechanisms. Our findings support the hypothesised involvement of α1-adrenoceptors in some of the cognitive-enhancing effects of Modafinil and warrant further investigation.
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Modafinil improves cognition and response inhibition in adult attention deficit hyperactivity disorder
Biological Psychiatry, 2004Co-Authors: Danielle C Turner, Trevor W Robbins, Luke Clark, J H Dowson, Barbara J SahakianAbstract:BACKGROUND: Modafinil, a novel cognitive enhancer, has a clinical profile similar to conventional stimulants such as methylphenidate, despite a seemingly different mechanism of action. Modafinil selectively improves neuropsychological task performance in healthy volunteers, possibly through improved inhibitory control. We examined whether Modafinil induced similar improvements in adults with attention-deficit/hyperactivity disorder. METHODS: Twenty patients with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were entered into a double-blind, randomized, placebo-controlled crossover study using a single 200 mg dose of Modafinil. RESULTS: Modafinil produced a similar pattern of cognitive enhancement to that observed in healthy adults, with improvements on tests of short-term memory span, visual memory, spatial planning, and stop-signal motor inhibition. On several measures, increased accuracy was accompanied by slowed response latency. This alteration in the speed-accuracy trade-off may indicate that Modafinil increases the ability to "reflect" on problems coupled with decreased impulsive responding. Improvements were also seen in sustained attention, which was unaffected in healthy subjects. CONCLUSIONS: If these benefits are shown to be maintained with chronic administration, Modafinil may have potential as an important therapy for attention-deficit/hyperactivity disorder with a similar effect to stimulants such as methylphenidate in improving stop-signal response inhibition but without the side effects commonly experienced with amphetamine-like drugs.
Joseph Biederman - One of the best experts on this subject based on the ideXlab platform.
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Modafinil improves symptoms of attention deficit hyperactivity disorder across subtypes in children and adolescents
The Journal of Pediatrics, 2008Co-Authors: Joseph Biederman, Steven R PliszkaAbstract:Objective This secondary analysis evaluated the efficacy of Modafinil in children and adolescents by subtype of attention-deficit/hyperactivity disorder (ADHD) using pooled data from 3 double-blind, placebo-controlled studies. Study design The patients were boys and girls age 6 to 17 years. ADHD subtype diagnoses (ie, inattentive, hyperactive-impulsive, combined) were based on criteria published in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Patients received Modafinil (170 to 425 mg) or placebo once daily for 7 to 9 weeks. Efficacy assessment used the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School and Home Versions, Clinical Global Impression of Improvement scale (CGI-I), and Conners’ Parent Rating Scale-Revised: Short Form (CPRS-R:S). Results A total of 638 patients received Modafinil (n = 423) or placebo (n = 215). The inattentive, hyperactive-impulsive, and combined subtypes included 187 (30%), 27 (4%), and 403 (65%) patients, respectively. Modafinil (vs placebo) significantly improved mean total scores for the ADHD-RS-IV School and Home Versions for the inattentive (change from baseline: School, Modafinil, −15.7, placebo, −7.1; Home, Modafinil, −13.8, placebo, −5.9) and combined subtypes (School, −16.5 vs −8.8; Home, −15.7 vs −7.6). Modafinil was associated with greater improvements on the CGI-I and improved CPRS-R:S subscale scores in inattentive and combined subtypes. Conclusions Modafinil improved ADHD symptoms and behaviors in patients with the inattentive and combined subtypes as determined by teachers, investigators, and parents.
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a comparison of once daily and divided doses of Modafinil in children with attention deficit hyperactivity disorder a randomized double blind and placebo controlled study
The Journal of Clinical Psychiatry, 2006Co-Authors: Joseph Biederman, James M Swanson, Craig Q Earl, Sharon B Wigal, Samuel W Boellner, Frank A LopezAbstract:Objective: This randomized, double-blind, placebo-controlled study assessed the efficacy and tolerability of several Modafinil dosing regimens in children with attention-deficit/ hyperactivity disorder (ADHD) to determine whether Modafinil can be given once daily in pediatric ADHD. Method: Children and adolescents (age range, 6-13 years) (N = 248) with DSM-IV-defined ADHD were enrolled in a 4-week, double-blind, placebo-controlled study, conducted February-May 2002. The group was assigned to receive oral (100-mg tablets) Modafinil 300 mg once daily (300 mg in the morning followed by placebo at midday), Modafinil 300 mg as a divided dose (100/200 mg or 200/100 mg), or matching placebo. In children weighing ≥ 30 kg, a higher dose of 400 mg (200/200 mg) was evaluated. Efficacy measures included the teacher-rated School Version and clinician-rated Home Version of the ADHD Rating Scale-IV and the parent-completed Conners' ADHD/DSM-IV Scales. Results: 223 children completed the study. Those who received Modafinil 300 mg once daily showed a significantly greater improvement (change from baseline) than those who received placebo in symptoms of ADHD across all rating scales and subscales (all p <.05). Divided 300-mg doses of Modafinil provided some significant but inconsistent improvements in ADHD symptoms. In children weighing ≥ 30 kg, Modafinil 400 mg (200/200 mg) was significantly superior to placebo on clinician- and parent-completed scales (all p <.05). Insomnia was the only adverse event to occur with significantly greater frequency in a Modafinil group (200/100) than in the placebo group (14% vs. 2%) (p =.03). Conclusion: Modafinil significantly improved ADHD symptoms in children. Once-daily dosing (300 mg) provided the most consistent improvement in symptoms. All dosing regimens of Modafinil were well tolerated.
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Modafinil film coated tablets in children and adolescents with attention deficit hyperactivity disorder results of a randomized double blind placebo controlled fixed dose study followed by abrupt discontinuation
The Journal of Clinical Psychiatry, 2006Co-Authors: James M Swanson, Laurence L Greenhill, Frank A Lopez, Andrew Sedillo, Craig Q Earl, John G Jiang, Joseph BiedermanAbstract:OBJECTIVE: The objective of this fixed-dose study was to determine the efficacy and safety of a new formulation of Modafinil (Modafinil film-coated tablets) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). In addition, the effect of abrupt discontinuation of Modafinil was evaluated in a 2-week observation period. METHOD: Patients aged 6 to 17 years with DSM-IV-TR-defined ADHD were randomly assigned to 7 weeks of double-blind treatment with Modafinil or placebo in a 2:1 ratio, followed by abrupt discontinuation of Modafinil and a 2-week, double-blind observation period in which 46% of patients receiving Modafinil were switched to placebo without tapering and half continued to receive Modafinil. Study drug was administered once daily and titrated over the first 7 to 9 days to daily doses of 340 mg for patients or = 30 kg. Assessment instruments included the Attention-Deficit/ Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global Impressions-Improvement scale (CGI-I). The study was conducted from November 2003 to June 2004. RESULTS: A total of 190 patients were randomly assigned to receive Modafinil (340 mg, N = 44; 425 mg, N = 82) or placebo (N = 64). 189 patients were evaluated for safety. Modafinil significantly improved symptoms of ADHD as shown by reductions in ADHD-RS-IV School Version total scores compared with placebo at all visits (p < or = .009), including the final visit of the double-blind phase (p < .0001). With Modafinil, ADHD-RS-IV School Version mean total scores changed from 37.8 at baseline to 29.3 at week 1 and 20.7 at final visit; corresponding placebo values were 36.6, 32.8, and 28.4, respectively; effect size at final visit was 0.76 (95% CI = 0.63 to 0.88). Total scores on the ADHD-RS-IV Home Version were also significantly reduced at all visits (p < or = .022) and final visit (p = .001) in patients receiving Modafinil compared with those receiving placebo. Significantly higher proportions of patients receiving Modafinil were rated "much improved" or "very much improved" in overall clinical condition (CGI-I) at all visits compared with patients receiving placebo (p < .001). No withdrawal symptoms were observed when Modafinil was abruptly discontinued at the beginning of the final 2-week observation period. Modafinil was generally well tolerated. Insomnia, headache, and decreased appetite were the most commonly reported adverse events. Sixty-three percent of patients who received Modafinil completed the study; 13% discontinued because of lack of efficacy; 10%, because of adverse events; and 13%, for other reasons (e.g., consent withdrawn, lost to follow-up). CONCLUSION: Modafinil significantly improved symptoms of ADHD both at school and at home and was well tolerated by children and adolescents. Abrupt discontinuation of Modafinil was not associated with symptoms of withdrawal or with rebound of symptoms of ADHD.
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efficacy and safety of Modafinil film coated tablets in children and adolescents with attention deficit hyperactivity disorder results of a randomized double blind placebo controlled flexible dose study
Pediatrics, 2005Co-Authors: Joseph Biederman, James M Swanson, Craig Q Earl, John G Jiang, Sharon B Wigal, Christopher J Kratochvil, Samuel W Boellner, Laurence L GreenhillAbstract:Objective. Modafinil, which is structurally and pharmacologically different from other agents that are used for the treatment of children with attention-deficit/hyperactivity disorder (ADHD), selectively activates the cortex and has low potential for abuse. Initial studies of the use of Modafinil to treat ADHD showed significant improvements in the core symptoms of the disorder, namely inattention, hyperactivity, and impulsivity. This study evaluated a new formulation of Modafinil (Modafinil film–coated tablets) in children and adolescents with ADHD. Methods. This 9-week, multicenter, randomized, double-blind, placebo-controlled, flexible-dose study evaluated the film-coated tablet formulation of Modafinil, which was titrated to an optimal dose on the basis of efficacy and tolerability (range: 170–425 mg once daily). Efficacy was assessed by clinicians who completed the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) based on interviews with teachers (School Version) and parents (Home Version) and the Clinical Global Impression of Improvement scale. Safety evaluation was based on assessments of adverse event reports, laboratory tests, vital signs, and body weight. Results. A total of 248 subjects were randomly assigned in a 2:1 ratio, and 246 were treated with Modafinil ( n = 164) or placebo ( n = 82). Treatment groups were comparable with respect to demographics and baseline characteristics. Intention-to-treat analysis (ITT) showed that compared with placebo, treatment with Modafinil significantly improved the core symptoms of ADHD as shown by greater reductions in the ADHD-RS-IV School Version total scores from baseline to final visit (mean change [SD]: −15.0 [11.8] vs −7.3 [9.7]) (effect size: 0.69; 95% confidence interval: 0.57–0.82). Significant improvements were observed with Modafinil treatment on the ADHD-RS-IV School Version at week 1, with improvements maintained throughout the study. Similar differences in symptom improvements were observed on the ADHD-RS-IV Home Version between Modafinil-treated and placebo-treated patients. Treatment with Modafinil also significantly reduced subscale scores for inattention and hyperactivity-impulsivity on both School and Home Versions compared with placebo. At the final visit, 48% of Modafinil-treated patients were rated as “much” or “very much” improved in overall clinical condition compared with 17% of placebo-treated patients (Clinical Global Impression of Improvement). Most adverse events were mild to moderate in severity, and the majority resolved during treatment. The most commonly reported adverse events in the Modafinil group were insomnia (29%), headache (20%), and decreased appetite (16%). Three percent of Modafinil-treated patients and 4% of placebo-treated patients discontinued treatment because of adverse events. Conclusions. Modafinil film–coated tablets significantly improved ADHD symptoms at school and home as evaluated by clinicians, teachers, and parents. Treatment with once-daily Modafinil was generally well tolerated, with few discontinuations as a result of adverse events.
William C Houghton - One of the best experts on this subject based on the ideXlab platform.
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sodium oxybate improves excessive daytime sleepiness in narcolepsy
Sleep, 2006Co-Authors: Jed Black, William C HoughtonAbstract:STUDY OBJECTIVES: To assess the effectiveness of sodium oxybate therapy, Modafinil therapy and the combination of the two for excessive daytime sleepiness in narcolepsy patients previously taking Modafinil. DESIGN: Double-blind, placebo-controlled, multicenter study. SETTING: Forty-four sites in the United States, Canada, the Czech Republic, France, Germany, the Netherlands, Switzerland, and the United Kingdom. PARTICIPANTS: Two hundred seventy- adult patients with narcolepsy taking 200 to 600 mg of Modafinil daily for the treatment of excessive daytime sleepiness. INTERVENTIONS: Patients received unchanged doses of Modafinil (with sodium-oxybate placebo) during a 2-week baseline phase. Following a baseline polysomnogram and Maintenance of Wakefulness Test, they were randomly assigned to 1 of 4 treatment groups: sodium-oxybate placebo plus Modafinil placebo, sodium oxybate plus Modafinil placebo, Modafinil plus sodium-oxybate placebo, or sodium oxybate plus Modafinil. Sodium oxybate was administered as 6 g nightly for 4 weeks and was then increased to 9 g nightly for 4 additional weeks. The primary efficacy measure was the Maintenance of Wakefulness Test; secondary measures included the Epworth Sleepiness Scale, diary recordings, and the Clinical Global Impression-change scale. RESULTS: Following the switch from Modafinil to placebo, the mean average daytime sleep latency on the Maintenance of Wakefulness Test decreased from 9.74 minutes at baseline to 6.87 minutes after 8 weeks (p < .001). In the sodium-oxybate group, there was no decrease in sleep latency, suggesting that this drug was as efficacious in treating the excessive daytime sleepiness as the previously administered Modafinil. In contrast, the sodium-oxybate/Modafinil group demonstrated an increase in daytime sleep latency from 10.43 minutes to 13.15 minutes (p < .001), suggesting that this combination of drugs produced an additive effect. The sodium-oxybate group also demonstrated a decrease in median average Epworth Sleepiness Scale scores, from 15 to 12.0, whereas the sodium-oxybate/Modafinil group decreased from 15.0 to 11.0 (for both, p < .001). The Clinical Global Impression-Change scale demonstrated similar results. CONCLUSIONS: Sodium oxybate and Modafinil are both effective for treating excessive daytime sleepiness in narcolepsy, producing additive effects when used together. Sodium oxybate is beneficial as both monotherapy and as adjunctive therapy for the treatment of excessive daytime sleepiness in narcolepsy.
Monica L Andersen - One of the best experts on this subject based on the ideXlab platform.
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dopamine transporter related effects of Modafinil in rhesus monkeys
Psychopharmacology, 2010Co-Authors: Monica L Andersen, Eileen Kessler, Kevin S Murnane, Jessica Mcclung, Sergio Tufik, Leonard L HowellAbstract:Modafinil is currently used as a treatment for daytime sleepiness. The objectives of this study were to explore the dopamine transporter (DAT)-related effects of Modafinil on behavior and in vivo neurochemistry in rhesus monkeys (Macaca mulatta). The effects of Modafinil (3.0–10 mg/kg, i.v.) were evaluated on locomotor activity, reinstatement of cocaine-maintained behavior, extracellular dopamine levels in the caudate nucleus, and DAT occupancy in the dorsal striatum. Eight subjects were fitted with a collar-mounted activity monitor to evaluate sleep-activity cycles, with 4 days of baseline recording preceding an injection of saline or Modafinil (3.0–10 mg/kg). The effects of Modafinil (3.0–10 mg/kg) and cocaine (0.3 mg/kg) on reinstatement of behavior that was previously maintained under a second-order schedule of i.v. cocaine delivery were tested in a separate group of subjects (n = 6). Finally, the effects of Modafinil (3.0–10 mg/kg) on extracellular dopamine levels and DAT occupancy in vivo were characterized using microdialysis and positron emission tomography, respectively, in a within-subjects design (n = 4). Modafinil significantly increased nighttime locomotor activity and reinstated cocaine-maintained behavior but did not affect daytime locomotor activity. Modafinil significantly increased striatal extracellular dopamine levels at a dose that resulted in DAT occupancy of 64.4% (putamen) and 60.2% (caudate). The behavioral and in vivo dopaminergic effects of Modafinil are consistent with the profile of a low potency DAT inhibitor and may indicate potential for abuse at high doses.