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Schizophrenia Research Mar 2012A prior 4-week, proof-of-concept study suggested that adjunctive therapy with armodafinil 200mg/day decreases negative symptoms in patients with clinically stable... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
A prior 4-week, proof-of-concept study suggested that adjunctive therapy with armodafinil 200mg/day decreases negative symptoms in patients with clinically stable schizophrenia. This study investigated the efficacy and tolerability of adjunctive armodafinil for treatment of negative symptoms in adults with schizophrenia receiving antipsychotic medications.
METHODS
This parallel-group, 24-week study enrolled adults with schizophrenia who were receiving oral olanzapine, risperidone, or paliperidone for ≥ 6 weeks, and had a Positive and Negative Syndrome Scale (PANSS) negative symptom subscale score of ≥ 15. Patients received one of 3 doses of once-daily armodafinil (150 mg, 200mg, or 250 mg) or placebo. The primary efficacy measure was the change from baseline to final visit in the PANSS negative symptom subscale score. Secondary measures included the PANSS total score, Clinical Global Impression of Severity, Personal and Social Performance Scale, and CNSVitalSigns cognitive battery.
RESULTS
Of 285 randomized patients, 213 received armodafinil and 72 received placebo. The mean (SD) changes in PANSS negative symptom subscale score were -1.9 (3.8) for armodafinil 150 mg (n = 70), -2.3 (3.6) for armodafinil 200mg (n = 69), -2.0 (3.3) for armodafinil 250 mg (n = 71), and -2.2 (4.1) for placebo (n=70) (p ≥ 0.70 for each armodafinil group versus placebo). Secondary measures were generally not different between groups. Armodafinil was generally well tolerated, without worsening positive symptoms.
CONCLUSIONS
This study found no benefit of adjunctive armodafinil versus placebo for negative symptoms in patients with schizophrenia receiving treatment with olanzapine, risperidone, or paliperidone. Armodafinil was generally well tolerated in these patients.
Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzhydryl Compounds; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Modafinil; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Young Adult
PubMed: 22178084
DOI: 10.1016/j.schres.2011.11.006 -
Molecular Psychiatry Apr 2023Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has...
Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.
Topics: Adult; Child, Preschool; Female; Humans; Infant; Pregnancy; Amphetamines; Attention Deficit Disorder with Hyperactivity; Clonidine; Cohort Studies; Denmark; Gestational Age; Methylphenidate; Modafinil; Mothers; Neurodevelopmental Disorders; Prenatal Exposure Delayed Effects; Registries
PubMed: 36759544
DOI: 10.1038/s41380-023-01992-6 -
Science Advances Jun 2023The efficacy of pharmaceutical cognitive enhancers in everyday complex tasks remains to be established. Using the knapsack optimization problem as a stylized...
The efficacy of pharmaceutical cognitive enhancers in everyday complex tasks remains to be established. Using the knapsack optimization problem as a stylized representation of difficulty in tasks encountered in daily life, we discover that methylphenidate, dextroamphetamine, and modafinil cause knapsack value attained in the task to diminish significantly compared to placebo, even if the chance of finding the optimal solution (~50%) is not reduced significantly. Effort (decision time and number of steps taken to find a solution) increases significantly, but productivity (quality of effort) decreases significantly. At the same time, productivity differences across participants decrease, even reverse, to the extent that above-average performers end up below average and vice versa. The latter can be attributed to increased randomness of solution strategies. Our findings suggest that "smart drugs" increase motivation, but a reduction in quality of effort, crucial to solve complex problems, annuls this effect.
Topics: Humans; Cognition; Methylphenidate; Modafinil; Motivation; Central Nervous System Stimulants
PubMed: 37315143
DOI: 10.1126/sciadv.add4165 -
European Journal of Neurology Sep 2021Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based...
BACKGROUND AND AIM
Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children.
METHODS
The European Academy of Neurology (EAN), European Sleep Research Society (ESRS) and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach.
RESULTS
A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong), methylphenidate, amphetamine derivates (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) excessive daytime sleepiness in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivates (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions.
CONCLUSION
The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.
Topics: Adult; Cataplexy; Child; Humans; Modafinil; Narcolepsy; Sleep; Sodium Oxybate
PubMed: 34173695
DOI: 10.1111/ene.14888 -
Human Brain Mapping Oct 2022Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional... (Randomized Controlled Trial)
Randomized Controlled Trial
Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant-induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large-scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism.
Topics: Adult; Brain; Brain Mapping; Caffeine; Central Nervous System Stimulants; Cognition; Double-Blind Method; Humans; Magnetic Resonance Imaging; Male; Methylphenidate; Modafinil; Neural Pathways
PubMed: 35670369
DOI: 10.1002/hbm.25949 -
Armodafinil for sarcoidosis-associated fatigue: a double-blind, placebo-controlled, crossover trial.Journal of Pain and Symptom Management Feb 2013Fatigue has been identified in more than one-half of patients with sarcoidosis. Although fatigue is not synonymous with impaired quality of life, most studies of... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Fatigue has been identified in more than one-half of patients with sarcoidosis. Although fatigue is not synonymous with impaired quality of life, most studies of sarcoidosis identify fatigue as a major cause of impaired quality of life.
OBJECTIVES
To test the hypothesis that stimulants may have a role in the treatment of fatigued sarcoidosis patients, even without objective evidence of daytime sleepiness.
METHODS
This was a double-blind, placebo-controlled, crossover study of sarcoidosis patients followed up in one sarcoidosis clinic Sarcoidosis patients with fatigue received either armodafinil or placebo with eight weeks of therapy for each arm and a two week washout period before crossover to the other treatment. Initial armodafinil dose was 150mg and increased to 250mg after four weeks. Patients underwent polysomnography and multiple sleep latency testing (MSLT) the following day. Patients with an apnea/hypopnea index <6/hour received either armodafinil or placebo. Polysomnography with MSLT was repeated after each treatment arm.
RESULTS
Fifteen patients received the study drug. Fatigue was assessed using the Fatigue Assessment Scale (the lower the score, the less the fatigue) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) (the higher the score, the less the fatigue). After eight weeks of therapy, there was a significant improvement in the Fatigue Assessment Scale during armodafinil treatment (median -4.5, range -20, 5) compared with placebo treatment (median 3.5, range -9, 14, P<0.05) and for the FACIT-F (armodafinil: median 9, range -12, 26 vs. placebo: median -5, range -17, 11, P<0.005). This improvement in fatigue was seen for both those with and without shortened sleep onset latency time during the MSLT.
CONCLUSION
Armodafinil treatment led to a significant reduction in fatigue in sarcoidosis patients. This effect was seen even in patients who did not have excessive daytime somnolence.
Topics: Adult; Benzhydryl Compounds; Central Nervous System Stimulants; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Humans; Male; Middle Aged; Modafinil; Placebo Effect; Sarcoidosis; Sleep Apnea Syndromes; Treatment Outcome
PubMed: 22917711
DOI: 10.1016/j.jpainsymman.2012.02.016 -
Journal of Clinical Sleep Medicine :... May 2018We present the case of a 21-year-old woman in whom Stevens-Johnson syndrome (SJS) developed after initiation of armodafinil. Although this rare and life-threatening...
We present the case of a 21-year-old woman in whom Stevens-Johnson syndrome (SJS) developed after initiation of armodafinil. Although this rare and life-threatening reaction is listed on armodafinil's label, no cases have been reported in the literature. This case, in addition to an update of the drug's label after post-marketing research, both support the link between armodafinil and SJS. Providers should maintain a high clinical suspicion for SJS when starting therapy to minimize associated morbidity and mortality by discontinuing armodafinil at the onset of first symptoms.
Topics: Female; Humans; Idiopathic Hypersomnia; Modafinil; Skin; Stevens-Johnson Syndrome; Wakefulness-Promoting Agents; Young Adult
PubMed: 29734973
DOI: 10.5664/jcsm.7132 -
Clinical Drug Investigation 2009Armodafinil, a non-amphetamine, wakefulness-promoting medication, is the R- and longer-lasting isomer of racemic modafinil. Armodafinil has been shown to improve... (Comparative Study)
Comparative Study
Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies.
BACKGROUND AND OBJECTIVE
Armodafinil, a non-amphetamine, wakefulness-promoting medication, is the R- and longer-lasting isomer of racemic modafinil. Armodafinil has been shown to improve wakefulness in patients with excessive sleepiness (ES) associated with treated obstructive sleep apnoea, shift work disorder or narcolepsy. In comparison with modafinil, armodafinil maintains higher plasma concentrations later in the day in healthy subjects. The objective of this analysis was to characterize the pharmacokinetic parameters related to those higher concentrations.
METHODS
Data from three randomized studies in healthy adult subjects receiving single doses of either armodafinil (50, 100, 200, 250, 300 or 400 mg) or modafinil (400 mg) were pooled, and subsequently dose-normalized to a 200 mg dose for each drug. Non-compartmental pharmacokinetic parameters were assessed.
RESULTS
Armodafinil and modafinil both had a mean single-dose terminal elimination half-life of approximately 13 hours, with similar mean maximum plasma drug concentration (C(max)) and median time to C(max) values. After reaching C(max), plasma concentrations appeared to decline in a monophasic manner with armodafinil, but in a biphasic manner with modafinil due to the initial rapid elimination of its S-isomer. As a result, mean area under the plasma drug concentration versus time curve (AUC) from time zero to the time of the last measurable concentration (AUC(last)) and AUC from time zero to infinity (AUC(infinity)) values were 33% and 40% higher, respectively, with armodafinil compared with modafinil on a milligram-to-milligram basis.
CONCLUSIONS
Despite similar half-lives, plasma concentrations following armodafinil administration are higher late in the day than those following modafinil administration on a milligram-to-milligram basis. The different pharmacokinetic profile of armodafinil may result in improved wakefulness throughout the day in patients with ES compared with modafinil.
Topics: Adolescent; Adult; Benzhydryl Compounds; Central Nervous System Stimulants; Female; Half-Life; Humans; Male; Middle Aged; Modafinil; Randomized Controlled Trials as Topic; Stereoisomerism; Time Factors
PubMed: 19663523
DOI: 10.2165/11315280-000000000-00000 -
Journal of Clinical Sleep Medicine :... Sep 2021This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
INTRODUCTION
This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to each recommendation, based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations.
RECOMMENDATIONS
The following recommendations are intended to guide clinicians in choosing a specific treatment for central disorders of hypersomnolence in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the individual patient's values and preferences to determine the best course of action. Under each disorder, strong recommendations are listed in alphabetical order followed by the conditional recommendations in alphabetical order. The section on adult patients with hypersomnia because of medical conditions is categorized based on the clinical and pathological subtypes identified in ICSD-3. The interventions in all the recommendation statements were compared to no treatment.
1
We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG).
2
We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG).
3
We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG).
4
We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG).
5
We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL).
6
We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL).
7
We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL).
8
We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG).
9
We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
10
We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
11
We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
12
We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
13
We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL).
14
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL).
15
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
16
We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
17
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
18
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
19
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL).
20
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL).
21
We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
22
We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
CITATION
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. . 2021;17(9):1881-1893.
Topics: Adult; Child; Disorders of Excessive Somnolence; Humans; Idiopathic Hypersomnia; Modafinil; Narcolepsy; Sleep; United States
PubMed: 34743789
DOI: 10.5664/jcsm.9328 -
British Journal of Pharmacology May 2019Sleep deprivation compromises learning and memory in both humans and animals, and can be reversed by administration of modafinil, a drug promoting wakefulness....
BACKGROUND AND PURPOSE
Sleep deprivation compromises learning and memory in both humans and animals, and can be reversed by administration of modafinil, a drug promoting wakefulness. Dysfunctional autophagy increases activation of apoptotic cascades, ultimately leading to increased neuronal death, which can be alleviated by autophagy inhibitors. This study aimed to investigate the alleviative effect and mechanism of modafinil on the excessive autophagy occurring in the hippocampus of mice with deficiency of learning and memory induced by sleep deprivation.
EXPERIMENTAL APPROACH
The Morris water maze was used to assess the effects of modafinil on male C57BL/6Slac mice after 48-hr sleep deprivation. The HT-22 hippocampal neuronal cell line was also used. Nissl staining, transmission electron microscope, immunofluorescence, Western blot, transient transfection, and autophagy inducer were used to study the effect and mechanism of modafinil on hippocampal neurons with excessive autophagy and apoptosis.
KEY RESULTS
Modafinil improved learning and memory in sleep-deprived mice, associated with the inhibition of excessive autophage and apoptosis and an enhanced activation of the PI3K/Akt/mTOR/P70S6K signalling pathway in hippocampal neurons. These effects of modafinil were abolished by rapamycin. In addition, modafinil suppressed the aberrant autophagy and apoptosis induced by rapamycin and reactivated PI3K/Akt/mTOR/P70S6K signals in HT-22 cells.
CONCLUSIONS AND IMPLICATIONS
These results suggested that modafinil alleviated impaired learning and memory of sleep-deprived mice potentially by suppressing excessive autophagy and apoptosis of hippocampal neurons. This novel mechanism may add to our knowledge of modafinil in the clinical treatment of impaired memory caused by sleep loss.
Topics: Animals; Apoptosis; Autophagy; Central Nervous System Stimulants; Hippocampus; Male; Mice; Mice, Inbred C57BL; Modafinil; Neurons; Protective Agents; Sleep Deprivation
PubMed: 30767208
DOI: 10.1111/bph.14626