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Substance Abuse 2020Modafinil is a nonamphetamine nootropic drug with an increasingly therapeutic interest due to its different sites of action and behavioral effects in comparison to... (Review)
Review
Modafinil is a nonamphetamine nootropic drug with an increasingly therapeutic interest due to its different sites of action and behavioral effects in comparison to cocaine or amphetamine. A review of modafinil (and of its prodrug adrafinil and its -enantiomer armodafinil) chemical, pharmacokinetic, pharmacodynamic, toxicological, clinical and forensic aspects was performed, aiming to better understand possible health problems associated to its unconscious and unruled use. Modafinil is a racemate metabolized mainly in the liver into its inactive acid and sulfone metabolites, which undergo primarily renal excretion. Although not fully clarified, major effects seem to be associated to inhibition of dopamine reuptake and modulation of several other neurochemical pathways, namely noradrenergic, serotoninergic, orexinergic, histaminergic, glutamatergic and GABAergic. Due its wake-promoting effects, modafinil is used for the treatment of daily sleepiness associated to narcolepsy, obstructive sleep apnea and shift work sleep disorder. Its psychotropic and cognitive effects are also attractive in several other pathologies and conditions that affect sleep structure, induce fatigue and lethargy, and impair cognitive abilities. Additionally, in health subjects, including students, modafinil is being used off-label to overcome sleepiness, increase concentration and improve cognitive potential. The most common adverse effects associated to modafinil intake are headache, insomnia, anxiety, diarrhea, dry mouth and raise in blood pressure and heart rate. Infrequently, severe dermatologic effects in children, including maculopapular and morbilliform rash, erythema multiforme and Stevens-Johnson Syndrome have been reported. Intoxication and dependence associated to modafinil are uncommon. Further research on effects and health implications of modafinil and its analogs is steel needed to create evidence-based policies.
Topics: Anxiety; Diarrhea; Drug Eruptions; Drug Interactions; Erythema Multiforme; Forensic Sciences; Headache; Humans; Modafinil; Narcolepsy; Nootropic Agents; Sleep Apnea, Obstructive; Sleep Disorders, Circadian Rhythm; Sleep Initiation and Maintenance Disorders; Stevens-Johnson Syndrome
PubMed: 31951804
DOI: 10.1080/08897077.2019.1700584 -
Journal of Neuroimmune Pharmacology :... Jun 2023To evaluate the ameliorating effect of Modafinil on neuroinflammation, behavioral, and histopathological alterations in rats induced by propionic acid (PPA). Thirty male...
To evaluate the ameliorating effect of Modafinil on neuroinflammation, behavioral, and histopathological alterations in rats induced by propionic acid (PPA). Thirty male Wistar rats were used in the study, divided into 3 groups of ten subjects. One group served as a control, the subjects in the other two were given 250 mg/kg/day of PPA by intraperitoneal injection over the course of 5 days to induce autism. The experimental design was as follows: Group 1: Normal control (orally-fed control, n = 10); Group 2 (PPA + saline, n = 10): PPA and 1 ml/kg/day % 0.9 NaCl saline via oral gavage; Group 3 (PPA + Modafinil, n = 10) PPA and 30 mg/kg/day Modafinil (Modiodal tablets 100 mg, Cephalon) via oral gavage. All of the groups were investigated for behavioral, biochemical, and histological abnormality. Autism-like behaviors were reduced significantly in the rats treated with PPA. TNF-α, Nerve Growth Factor (NGF), IL-17, IL-2, and NF-KB levels as well as MDA levels and lactate were significantly higher in those treated with PPA compared to the control group. Using immunohistochemical methods, the number of neurons and GFAP immunoreactivity was significantly altered in PPA-treated rats compared to the control. Using Magnetic Resonance Spectroscopy (MRS), we found that lactate levels were significantly higher in the PPA-treated rats, while creatinine levels were significantly decreased. In the rats administered with Modafinil, behavior, neuroinflammation, and histopathological changes brought about by PPA were significantly reversed. Our results demonstrate the potential role of Modafinil in ameliorating PPA-induced neuroinflammation in rats.
Topics: Rats; Male; Animals; Autistic Disorder; Modafinil; Neuroinflammatory Diseases; Rats, Wistar; Lactates
PubMed: 37043086
DOI: 10.1007/s11481-023-10061-2 -
Experimental Neurology Jan 2022Multiple sclerosis (MS) is a complex disorder characterized by a broad spectrum of symptoms that evolve throughout the disease. Symptoms can be categorized as visible... (Review)
Review
Multiple sclerosis (MS) is a complex disorder characterized by a broad spectrum of symptoms that evolve throughout the disease. Symptoms can be categorized as visible and invisible based on external sight recognition. However, although others poorly recognize it, invisible symptoms such as mood dysfunction, neuropathic pain, or fatigue can significantly affect activities of daily living and the quality of life of people with MS (PwMS). PwMS frequently complain of fatigue, which has physical or cognitive manifestations. Fatigue in MS does not improve or resolve with rest, and it is disproportionate with respect to the exerted effort. Fatigue management in MS is challenging, and a few pharmacological approaches have been successfully proposed. Among them, the drug modafinil has attracted attention because of its properties as a synthetic psychoactive drug. In this review, we focus on the evidence available to date, supporting the use of modafinil in MS fatigue. However, despite the availability of some trials evaluating the effects of modafinil on fatigue, their contrasting results failed to support its usefulness in fatigue management in MS.
Topics: Activities of Daily Living; Central Nervous System Stimulants; Fatigue; Humans; Modafinil; Multiple Sclerosis; Psychotropic Drugs; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34710403
DOI: 10.1016/j.expneurol.2021.113906 -
The Journal of Clinical Psychiatry Jun 2007
Topics: Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Central Nervous System Stimulants; Drug Industry; Drug Labeling; Humans; Modafinil; Substance-Related Disorders; United States; United States Food and Drug Administration
PubMed: 17592927
DOI: 10.4088/jcp.v68n0624b -
Psychopharmacology Aug 2022Modafinil has been proposed as a potentially effective clinical treatment for neuropsychiatric disorders characterized by cognitive control deficits. However, the...
RATIONALE
Modafinil has been proposed as a potentially effective clinical treatment for neuropsychiatric disorders characterized by cognitive control deficits. However, the precise effects of modafinil, particularly on brain network functions, are not completely understood.
OBJECTIVES
To address this gap, we examined the effects of modafinil on resting-state brain activity in 30 healthy adults using microstate analysis. Electroencephalographic (EEG) microstates are discrete voltage topographies generated from resting-state network activity.
METHODS
Using a placebo-controlled, within-subjects design, we examined changes to microstate parameters following placebo (0 mg), low (100 mg), and high (200 mg) modafinil doses. We also examined the functional significance of these microstates via associations between microstate parameters and event-related potential indexes of conflict monitoring and automatic error processing (N2 and error-related negativity) and behavioral responses (accuracy and RT) from a subsequent flanker interference task.
RESULTS
Five microstates emerged following each treatment condition, including four canonical microstates (A-D). Modafinil increased microstate C proportion and occurrence regardless of dose, relative to placebo. Modafinil also decreased microstate A proportion and microstate B proportion and occurrence relative to placebo. These modafinil-related changes in microstate parameters were not associated with similar changes in flanker ERPs or behavior. Finally, modafinil made transitions between microstates A and B less likely and transitions from A and B to C more likely.
CONCLUSIONS
Previous fMRI work has correlated microstates A and B with auditory and visual networks and microstate C with a salience network. Thus, our results suggest modafinil may deactivate large-scale sensory networks in favor of a higher order functional network during resting-state in healthy adults.
Topics: Adult; Brain; Cognition Disorders; Cognitive Dysfunction; Electroencephalography; Humans; Modafinil
PubMed: 35471613
DOI: 10.1007/s00213-022-06149-x -
Journal of Neurosurgical Sciences Aug 2023Modafinil has been proven to exert anti-inflammatory, anti-oxidative and neuroprotective effects on numerous neurological disorders. However, its effects after traumatic...
BACKGROUND
Modafinil has been proven to exert anti-inflammatory, anti-oxidative and neuroprotective effects on numerous neurological disorders. However, its effects after traumatic brain injury (TBI) have not been yet explored. The aim of this study was to explore if Modafinil can attenuate the neuroinflammatory phase of TBI and clarify the possible underlying mechanisms.
METHODS
A weight drop model was used to induce experimental TBI on 30 Wistar albino rats. The treatment group received Modafinil on the day of the trauma and the following 5 days. Garcia Test was used to assess for neurological status and histopathological examination along with biochemical analysis of NSE, S-100B, CASP3, and TBARS levels were performed.
RESULTS
Rats treated with Modafinil after the trauma had a statistically significant higher Garcia Test Score (P<0.001) and presented with increased evidence of anti-inflammatory and neuroprotective effect (P<0.05, P=0.005). Decreased levels of all biochemical parameters with NSE, CASP3, and TBARS having statistical significance was observed (P<0.05).
CONCLUSIONS
The findings of this paper support the notion that a psychoactive drug Modafinil, traditionally used for sleep disorders and also known as a cognitive enhancer may prove beneficial in decreasing mortality and morbidity after TBI through anti-inflammatory, anti-oxidative and neuroprotective effects.
Topics: Rats; Animals; Modafinil; Caspase 3; Neuroprotective Agents; Thiobarbituric Acid Reactive Substances; Rats, Wistar; Brain Injuries, Traumatic; Inflammation; Anti-Inflammatory Agents; Disease Models, Animal
PubMed: 34545730
DOI: 10.23736/S0390-5616.21.05382-0 -
Expert Review of Clinical Pharmacology Sep 2019: The current emphasis on combatting the opioid epidemic in the United States and across the globe is well warranted, but rates and variations of other drugs and... (Review)
Review
: The current emphasis on combatting the opioid epidemic in the United States and across the globe is well warranted, but rates and variations of other drugs and substances of abuse may be inadvertently increasing as well. These drugs and substances deserve equal attention in the literature to equip healthcare practitioners with the knowledge to provide optimal care in overdose patients. : This evaluation includes loperamide, gabapentin, and modafinil and was accomplished through a comprehensive literature review of PubMed, MEDLINE, SCOPUS, ProQuest Central, ProQuest Dissertations, and CINAHL. The results of forty-four pieces of literature are included in this evaluation. The objective of this review is to provide a repository of standard and emerging treatment modalities for loperamide, gabapentin and modafinil for the emergency medicine team. : Loperamide, gabapentin, and modafinil are becoming drugs of abuse, and as such, should be on the radar of healthcare providers. Recognizing their unique toxicity profiles is imperative in providing optimal resuscitative care.
Topics: Drug Overdose; Emergency Treatment; Gabapentin; Humans; Loperamide; Modafinil; Substance-Related Disorders
PubMed: 31422705
DOI: 10.1080/17512433.2019.1657830 -
Journal of Psychopharmacology (Oxford,... Sep 2023
Topics: Modafinil; Central Nervous System Stimulants; Benzhydryl Compounds
PubMed: 37435726
DOI: 10.1177/02698811231187127 -
Journal of Stroke and Cerebrovascular... Apr 2020Acute rehabilitation is known to enhance stroke recovery. However, poststroke lethargy and fatigue can hinder participation in rehabilitation therapies. We hypothesized...
BACKGROUND AND PURPOSE
Acute rehabilitation is known to enhance stroke recovery. However, poststroke lethargy and fatigue can hinder participation in rehabilitation therapies. We hypothesized that in patients with moderate to severe stroke complicated by poststroke fatigue and lethargy early stimulant therapy with modafinil increases favorable discharge disposition defined as transfer to acute inpatient rehabilitation or home.
METHODS
We retrospectively reviewed a cohort of patients with acute stroke admitted to the stroke service over a 3-year period. All patients 18 years or older with confirmed ischemic or hemorrhagic stroke, an NIHSS greater than or equal to 5 and documentation of fatigue/lethargy in clinical documentation were included. We compared patients that were treated with modafinil 50-200 mg to those managed with standard care. The primary outcome measure was discharge disposition. Secondary outcome was 90 day modified Rankin score (mRS). Statistical significance was determined using chi-square test for association and logistic regression models. Logistic regression models were derived in 2 ways with both raw data and an adjusted model that accounted for age, sex, and NIHSS score to account for the lack of randomization.
RESULTS
This study included 199 stroke patients (145 ischemic, 54 hemorrhagic). Seventy-two (36.2%) were treated with modafinil and 129 (64.8%) were discharged to acute inpatient rehabilitation, while none were recommended for discharge home. Median NIHSS for modafinil patients was 13.5 versus 11 for standard care patients (P = .059). In adjusted models, modafinil was associated with higher odds of favorable discharge disposition (OR 2.00, 95% CI 1.01-3.95). Favorable outcome at 90 days defined as mRS less than or equal to 2 occurred more frequently with modafinil (5.6% versus 3.3%) but this did not achieve statistical significance (P > .1). These results occurred despite the modafinil group requiring longer ICU stays and having more in-hospital complications such as infections and need for percutaneous gastrostomy tubes. The benefit of modafinil was seen across all subgroups except those with severe stroke (NIHSS ≥ 15). There were no significant adverse events associated with modafinil administration.
CONCLUSIONS
Modafinil use in acute in-hospital stroke patients with moderate stroke complicated by lethargy and fatigue was associated with improved discharge disposition. Randomized controlled trials are needed to further study the safety, efficacy, and long-term effects of modafinil in this patient population.
Topics: Aged; Aged, 80 and over; Central Nervous System Stimulants; Disability Evaluation; Fatigue; Female; Health Status; Humans; Lethargy; Male; Middle Aged; Modafinil; Recovery of Function; Retrospective Studies; Stroke; Stroke Rehabilitation; Time Factors; Treatment Outcome
PubMed: 32147025
DOI: 10.1016/j.jstrokecerebrovasdis.2020.104645 -
The Annals of Pharmacotherapy Oct 2006To review the evidence for the use of modafinil in the treatment of attention deficit/hyperactivity disorder (ADHD). (Review)
Review
OBJECTIVE
To review the evidence for the use of modafinil in the treatment of attention deficit/hyperactivity disorder (ADHD).
DATA SOURCES
A MEDLINE search (January 1990-May 2006) was conducted using MeSH terms ADHD and modafinil. The search was limited to English-language articles on clinical trials in humans. The Cochrane Database was also searched.
STUDY SELECTION AND DATA EXTRACTION
The literature search yielded 4 randomized clinical trials.
DATA SYNTHESIS
The use of modafinil in the treatment of ADHD is associated with significant improvements in primary outcome measures used to assess the status of patients diagnosed with ADHD. Several aspects of cognitive function in ADHD patients also appear to improve following modafinil treatment. Modafinil shows a favorable adverse effect profile. Insomnia and headache were the most common adverse effects, seen in approximately 20% of treated individuals. However, it has not been demonstrated that the beneficial effects of modafinil are maintained with chronic administration.
CONCLUSIONS
Modafinil may be a viable option for some patients in the treatment of ADHD, perhaps those for whom standard ADHD therapies have not been successful or tolerated. There remains a need for additional large, long-term studies using flexible titration methods to optimize the dose of modafinil to establish safety and efficacy, as well as head-to-head comparisons between modafinil and both long- and short-acting stimulants to determine the role of modafinil in the treatment of ADHD.
Topics: Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Humans; Modafinil
PubMed: 16954326
DOI: 10.1345/aph.1H024