-
Cureus Aug 2022[This corrects the article DOI: 10.7759/cureus.27287.].
[This corrects the article DOI: 10.7759/cureus.27287.].
PubMed: 38348022
DOI: 10.7759/cureus.c69 -
Cureus Jun 2022Introductionː Postoperative cognitive dysfunction has long-term consequences of increased mortality, loss of autonomy, and prolonged hospitalization. We sought to...
Introductionː Postoperative cognitive dysfunction has long-term consequences of increased mortality, loss of autonomy, and prolonged hospitalization. We sought to determine whether exposing patients to modafinil may attenuate or prevent this devastating syndrome from affecting the elderly postoperatively. Methodsː Adults aged 65 and older and American Society of Anesthesiologists (ASA) I-III physical status scheduled for elective noncardiac/non-neurosurgical surgery were included. Subjects were tested with the Trail Making Test (TMT) and Rey Auditory Visual Learning Test (RAVLT) preoperatively as well as in the immediate postoperative period, at 1 week, and at 3 months. After baseline testing, patients were randomized into three groups: 0) placebo pre and post-procedure; 1) modafinil only pre-procedure and placebo post-procedure; and 2) modafinil pre and post-procedure. A nonsurgical control group was also utilized. Resultsː Seventy-six subjects completed the trial 3 months post-surgery. The baseline RAVLT obtained was analyzed with 2-way ANOVA with repeated measures and showed improvement in learning in all groups (p = 0.03). At 1-week post-surgery, Group 0 subjects demonstrated no learning improvement in the RAVLT. However, there was a significant improvement in learning in both groups that received modafinil (p<0.01), and in the nonsurgical controls (p<0.01). This learning benefit normalized at 3 months. Conclusionː In this prospective, double-blind, placebo-controlled trial, we found that patients who received modafinil showed improvement in the RAVLT at 1 week. However, this learning benefit normalized at 3 months. Further study should examine dose effect, timing, and route of administration to determine if the effect can be enhanced and if in fact, wakefulness is improved post-surgically.
PubMed: 35891830
DOI: 10.7759/cureus.26204 -
Metabolites Jun 2022Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due...
Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due to its abuse by students and athletes, there is a need of its quantification. Quantitative analysis by liquid chromatography-mass spectrometry, however, though very common and sensitive, frequently cannot be performed without isotopically labeled standards which usually have to be specially synthesized. Here we reported our investigation on the preparation of deuterated standard of armodafinil based on the simple and inexpensive hydrogen-deuterium exchange reaction at the carbon centers. The obtained results clearly indicate the possibility of introduction of three deuterons into the armodafinil molecule. The introduced deuterons do not undergo back exchange under neutral and acidic conditions. Moreover, the deuterated and non-deuterated armodafinil isotopologues revealed co-elution during the chromatographic analysis. The ability to control the degree of deuteration using different reaction conditions was determined. The proposed method of deuterated armodafinil standard preparation is rapid, cost-efficient and may be successfully used in its quantitative analysis by LC-MS.
PubMed: 35888702
DOI: 10.3390/metabo12070578 -
Biomolecules Jun 2022Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young and senescent brains,...
Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young and senescent brains, including motricity, sleep, attention, emotion, learning and memory, and social and reward-seeking behaviors. The DA transporter (DAT) regulates transsynaptic DA levels, influencing all these processes. Compounds targeting DAT (e.g., cocaine and amphetamines) were historically used to shape mood and cognition, but these substances typically lead to severe negative side effects (tolerance, abuse, addiction, and dependence). DA/DAT signaling dysfunctions are associated with neuropsychiatric and progressive brain disorders, including Parkinson's and Alzheimer diseases, drug addiction and dementia, resulting in devastating personal and familial concerns and high socioeconomic costs worldwide. The development of low-side-effect, new/selective medicaments with reduced abuse-liability and which ameliorate DA/DAT-related dysfunctions is therefore crucial in the fields of medicine and healthcare. Using the rat as experimental animal model, the present work describes the synthesis and pharmacological profile of ()-MK-26, a new modafinil analogue with markedly improved potency and selectivity for DAT over parent drug. Ex vivo electrophysiology revealed significantly augmented hippocampal long-term synaptic potentiation upon acute, intraperitoneally delivered ()-MK-26 treatment, whereas in vivo experiments in the hole-board test showed only lesser effects on reference memory performance in aged rats. However, in effort-related FR5/chow and PROG/chow feeding choice experiments, ()-MK-26 treatment reversed the depression-like behavior induced by the dopamine-depleting drug tetrabenazine (TBZ) and increased the selection of high-effort alternatives. Moreover, in in vivo microdialysis experiments, ()-MK-26 significantly increased extracellular DA levels in the prefrontal cortex and in nucleus accumbens core and shell. These studies highlight ()-MK-26 as a potent enhancer of transsynaptic DA and promoter of synaptic plasticity, with predominant beneficial effects on effort-related behaviors, thus proposing therapeutic potentials for ()-MK-26 in the treatment of low-effort exertion and motivational dysfunctions characteristic of depression and aging-related disorders.
Topics: Animals; Dopamine; Dopamine Plasma Membrane Transport Proteins; Hippocampus; Humans; Motivation; Neuronal Plasticity; Rats
PubMed: 35883437
DOI: 10.3390/biom12070881 -
SAGE Open Medical Case Reports 2022Kleine-Levin syndrome (KLS) is an extremely rare relapsing-remitting neuropsychiatric condition characterized by recurrent incidents of major hypersomnolence along with...
Kleine-Levin syndrome (KLS) is an extremely rare relapsing-remitting neuropsychiatric condition characterized by recurrent incidents of major hypersomnolence along with hyperphagia, hypersexual behavior, and mood or cognitive disturbances alternating with asymptomatic periods. Here, we present a case of a young male chiefly presenting with recurring episodes of acute onset behavioral changes. The patient's episodes were characterized by repetitive incidents of prolonged sleep for more than 20 h, followed by social withdrawal and apathy. He was diagnosed with KLS because of the periodic patterns of hypersomnolence accompanied by other cognitive and mood disturbances and lacked characteristics of central hypersomnolence disorders or atypical depression. There are varying success rates among medications such as lithium, stimulants such as modafinil, antiepileptics such as carbamazepine and valproate. Similarly, the use of antidepressants such as tricyclic agents and selective serotonin reuptake inhibitors has largely been negative. Our case report addresses a patient with KLS who was successfully treated with 20 mg of Escitalopram.
PubMed: 35847426
DOI: 10.1177/2050313X221110985 -
Health Psychology Research 2022Narcolepsy is a debilitating sleep disorder that presents with excessive daytime sleepiness (EDS) and cataplexy, which is a sudden paralysis of muscle tone triggered by... (Review)
Review
Narcolepsy is a debilitating sleep disorder that presents with excessive daytime sleepiness (EDS) and cataplexy, which is a sudden paralysis of muscle tone triggered by strong emotions such as laughing. It is also associated with many other disorders, including psychiatric disorders, neurologic illnesses, and medication side effects. Common causes of delayed and incorrect diagnoses of these conditions include lack of physician familiarity with narcolepsy symptoms and comorbidities which mask narcolepsy signs and symptoms. Current pharmacologic therapies include Modafinil and Armodafinil for EDS and sodium oxybate for cataplexy. This review discusses the epidemiology, pathophysiology, risk factors, presentation, treatment of narcolepsy, and the role of a novel drug, Pitolisant, in the treatment of EDS in adults with narcolepsy. Pitolisant is a histamine-3 receptor (H3R), competitive antagonist, and inverse agonist, acting through the histamine system to regulate wakefulness. It is a novel drug approved in August 2019 by the FDA, is not classified as a controlled substance, and is approved for use in Europe and the United States to treat EDS and cataplexy in narcolepsy. Recent phase II and III trials have shown that Pitolisant helps reduce the ESS score and cataplexy. In summary, based on comparative studies, recent evidence has shown that Pitolisant is non-inferior to Modafinil in the treatment of EDS but superior to Modafinil in reducing cataplexy.
PubMed: 35774905
DOI: 10.52965/001c.34222 -
Neuropsychiatric Disease and Treatment 2022The acute phase of Coronavirus disease-19 (COVID-19) is well known. However, there is now an increasing number of patients suffering from the post-acute sequelae of...
BACKGROUND
The acute phase of Coronavirus disease-19 (COVID-19) is well known. However, there is now an increasing number of patients suffering from the post-acute sequelae of COVID-19 (PASC Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis), including neuropsychiatric symptoms. The purpose of this report is to describe the sociodemographic, diagnostic and treatment characteristics of patients evaluated in an outpatient psychiatric setting for PASC.
METHODS
A retrospective review of 30 individuals with documented COVID-19 illness treated at a university hospital-based Post-COVID-19 Recovery Program were referred to an outpatient psychiatric department for consultation and treatment from December 2020 to July 2021. All individuals complained of neuropsychiatric symptoms including anxiety, depression, fatigue and cognitive problems. Data on sociodemographic characteristics, psychiatric diagnosis, prominent psychological themes and treatment prescribed were described and, where applicable, analyzed with SPSS software.
RESULTS
The study population consisted of patients between 25 and 82 years old, with a predominance of women between 46 and 60 years. Approximately half of the patient population had a primary diagnosis of major depressive disorder, often combined with prominent anxiety. Over two-thirds of the patient population reported a combination of depression, fatigue and cognitive complaints, predominantly memory and slowed processing speed. Prominent stressors and psychological themes included social and occupational decline, isolation, lack of empathy and understanding from family, friends and employers, and apprehension about future ability to return to their baseline level of function. Treatments recommended included individual and group psychotherapy, medication and cognitive rehabilitation. Modafinil and antidepressants, often in combination, were the most commonly used medications, intended to target the pervasive fatigue, depressive, and anxiety these individuals were facing.
CONCLUSION
Clinical experience from this patient population underscored the significant medical, emotional, neurocognitive and functional sequelae of PASC. Management of these individuals requires a collaborative approach with the availability of psychotherapeutic interventions, pharmacologic treatment, neurocognitive assessment and remediation to address these symptoms.
PubMed: 35761861
DOI: 10.2147/NDT.S357262 -
International Journal of Molecular... Jun 2022The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However,...
The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D) expression and behavior (non-selective attention "NSA") in the mesocorticolimbic system of young healthy Sprague-Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.
Topics: Adolescent; Animals; Attention; Central Nervous System Stimulants; Glutamic Acid; Humans; Male; Modafinil; Nucleus Accumbens; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Ventral Tegmental Area; gamma-Aminobutyric Acid
PubMed: 35743046
DOI: 10.3390/ijms23126602 -
ARYA Atherosclerosis Nov 2021Pulmonary complications following cardiopulmonary bypass (CPB) pump during coronary artery bypass grafting (CABG) are relatively common and the incidence of cognitive...
BACKGROUND
Pulmonary complications following cardiopulmonary bypass (CPB) pump during coronary artery bypass grafting (CABG) are relatively common and the incidence of cognitive dysfunction is reported as ranging in rate from 30% to 80% in the early postoperative period. The purpose of this study was to assess the effect of modafinil administration on the prevention of pulmonary and cerebral complications and shortening the hospital stay after CABG surgery.
METHODS
This randomized double-blind intervention-controlled clinical trial was performed on 74 patients (37 in the intervention group and 37 in the control group) undertaking CABG surgery. The intervention group was orally treated with doses of 200 mg of modafinil on the day of surgery, and on the morning of the day after surgery, the second dose of modafinil 200 mg was given to patients. The control group underwent a placebo with the same intervals.
RESULTS
Administration of modafinil in intervention group significantly decreased the time to reach consciousness (P = 0.001), ventilator time in intensive care unit (ICU) (P < 0.001), length of stay in ICU (P = 0.009), duration of hospitalization (P = 0.008), and arterial blood carbon dioxide pressure (PaCO2) (P = 0.047). In the intervention group, no patients with delirium, agitation, respiratory depression, non-invasive respiratory ventilation, and endotracheal re-intubation were observed.
CONCLUSION
Modafinil tablet as a respiratory and brain stimulant through the central nervous system (CNS) can improve the quality of breathing and arterial blood gases (ABGs) and also can increase the level of consciousness and shorten the recovery time.
PubMed: 35685446
DOI: 10.22122/arya.v17i0.2371 -
Nicotine & Tobacco Research : Official... Jan 2023Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA...
Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA terminology), with the vast majority failing to show efficacy. Even small randomized clinical trials (RCTs), the most common early Phase 2 tests, are costly undertakings, made more unappealing by their high likelihood of failure. At the same time, another early Phase 2 approach, acute tests of drug effects on surrogate endpoints such as withdrawal or craving severity, are more practical but have little predictive clinical validity. Described here is an innovative procedure that optimally combines the validity of clinical trials with the practical advantages of surrogate endpoint studies to more efficiently determine whether or not a novel drug warrants continued clinical development. This CrEATE procedure, or Crossover Evaluation of Addiction Treatment Efficacy, does so by assessing short-term quit success in smokers highly motivated to quit when briefly treated with active drug versus placebo in a crossover design, so that quit efficacy from both conditions is compared within participants. The program to develop and evaluate CrEATE demonstrates its sensitivity to efficacy from all three FDA-approved first-line cessation medications (NRT, varenicline, bupropion), tested here as model drugs, as well as specificity in identifying lack of efficacy with a drug known to be ineffective for cessation (modafinil). CrEATE has subsequently been used to evaluate a few novel interventions, concluding they lack efficacy in increasing quit success. Future directions for the potential utility of CrEATE are provided. Implications: The ability of CrEATE to reach a Go/No Go decision more quickly and with far less cost lowers the risk of failure, meaning widespread use of the procedure should encourage the evaluation of more novel candidate drugs. With its greater efficiency, failed tests, unfortunately the most likely outcome in early Phase 2 studies, will cause less waste of resources. At the same time, CrEATE tests that indicate a novel treatment has efficacy will justify the substantial time and expense of moving forward to evaluate the drug in late Phase 2 RCTs.
Topics: Humans; Nicotinic Agonists; Cross-Over Studies; Benzazepines; Smoking; Varenicline; Bupropion; Treatment Outcome
PubMed: 35671343
DOI: 10.1093/ntr/ntac139