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Pharmacology, Biochemistry, and Behavior Aug 2011Whether drugs that enhance cognition in healthy individuals will appear in the near future has become a topic of considerable interest. We address this possibility using... (Review)
Review
Whether drugs that enhance cognition in healthy individuals will appear in the near future has become a topic of considerable interest. We address this possibility using a three variable system (psychological effect, neurobiological mechanism, and efficiency vs. capabilities) for classifying candidates. Ritalin and modafinil, two currently available compounds, operate on primary psychological states that in turn affect cognitive operations (attention and memory), but there is little evidence that these effects translate into improvements in complex cognitive processing. A second category of potential enhancers includes agents that improve memory encoding, generally without large changes in primary psychological states. Unfortunately, there is little information on how these compounds affect cognitive performance in standard psychological tests. Recent experiments have identified a number of sites at which memory drugs could, in principle, manipulate the cell biological systems underlying the learning-related long-term potentiation (LTP) effect; this may explain the remarkable diversity of memory promoting compounds. Indeed, many of these agents are known to have positive effects on LTP. A possible third category of enhancement drugs directed specifically at integrated cognitive operations is nearly empty. From a neurobiological perspective, two plausible candidate classes have emerged that both target the fast excitatory transmission responsible for communication within cortical networks. One acts on nicotinic receptors (alpha7 and alpha4) that regulate release of the neurotransmitter glutamate while the other ('ampakines') allosterically modulates the glutamate receptors mediating the post-synaptic response (EPSCs). Brain imaging in primates has shown that ampakines expand cortical networks engaged by a complex task; coupled with behavioral data, these findings provide evidence for the possibility of generating new cognitive capabilities. Finally, we suggest that continuing advances in behavioral sciences provide new opportunities for translational work, and that discussions of the social impact of cognitive enhancers have failed to consider the distinction between effects on efficiency vs. new capabilities.
Topics: Animals; Benzhydryl Compounds; Cognition; Humans; Long-Term Potentiation; Memory; Methylphenidate; Modafinil; Models, Neurological; Models, Psychological; Nootropic Agents; Translational Research, Biomedical
PubMed: 21215768
DOI: 10.1016/j.pbb.2010.12.024 -
Neurotherapeutics : the Journal of the... Jan 2021Narcolepsy is a rare, chronic, and disabling central nervous system hypersomnia; two forms can be recognized: narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Its... (Review)
Review
Narcolepsy is a rare, chronic, and disabling central nervous system hypersomnia; two forms can be recognized: narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Its etiology is still largely unknown, but studies have reported a strong association between NT1 and HLA, as well as a pathogenic association with the deficiency of cerebrospinal hypocretin-1. Thus, the most reliable pathogenic hypothesis is an autoimmune process destroying hypothalamic hypocretin-producing cells. A definitive cure for narcolepsy is not available to date, and although the research in the field is highly promising, up to now, current treatments have aimed to reduce the symptoms by means of different pharmacological approaches. Moreover, overall narcolepsy symptoms management can also benefit from non-pharmacological approaches such as cognitive behavioral therapies (CBTs) and psychosocial interventions to improve the patients' quality of life in both adult and pediatric-affected individuals as well as the well-being of their families. In this review, we summarize the available therapeutic options for narcolepsy, including the pharmacological, behavioral, and psychosocial interventions.
Topics: Behavior Therapy; Carbamates; Counseling; Humans; Modafinil; Narcolepsy; Phenylalanine; Piperidines; Wakefulness-Promoting Agents
PubMed: 33886090
DOI: 10.1007/s13311-021-01051-4 -
Turk Kardiyoloji Dernegi Arsivi : Turk... Jan 2022Modafinil is a central nervous system stimulant that promotes wakefulness and is approved for the treatment of narcolepsy and several other conditions. However, there is...
Modafinil is a central nervous system stimulant that promotes wakefulness and is approved for the treatment of narcolepsy and several other conditions. However, there is a big concern about drug abuse, especially among students to enhance cognitive performance and to reduce the need for sleep. In this case report, we present a 23-year-old female admitted to the cardiology outpatient clinic owing to recurrent palpitations. She stated that she started modafinil 100 mg twice a day one month earlier to increase performance while studying for her exams. Her electrocardiogram (ECG) demonstrated sinus rhythm and a right bundle branch block (RBBB). No structural heart disease or metabolic pathology was detected. A 24-hour ambulatory ECG record showed 11 attacks of non-sustained ventricular tachycardia (NSVT), the longest of which was eight beats. The drug was discontinued and two weeks later, the patient was symptom-free, and her control ECG showed normal sinus rhythm with no RBBB. A control ambulatory ECG was performed, and no ventricular tachycardia was observed. Modafinil, which is considered safer than amphetamine derivatives in terms of cardiovascular side effects, rarely causes serious arrhythmic events, even in healthy subjects. Thus, we suggest evaluating patients for cardiac symptoms after starting on modafinil, and they should be also interrogated regarding the abuse of this drug.
Topics: Adult; Arrhythmias, Cardiac; Bundle-Branch Block; Electrocardiography; Female; Humans; Modafinil; Tachycardia, Ventricular; Young Adult
PubMed: 35197237
DOI: 10.5543/tkda.2022.21084 -
The Cochrane Database of Systematic... Jan 2023Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality... (Review)
Review
BACKGROUND
Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review.
OBJECTIVES
To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index (ISI Web of Science), LILACS, and two clinical trial registries from inception to 18 July 2022. SELECTION CRITERIA: We included randomised controlled trials in adults aged ≥18 years. We included participants with advanced cancer who were suffering from CRF. We included trials that randomised participants to corticosteroids at any dose, by any route, administered for the relief of CRF; compared to placebo or an active comparator, including supportive care or non-pharmacological treatments.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed titles identified by the search strategy; two review authors assessed risk of bias; and two extracted data. We extracted the primary outcome of participant-reported fatigue relief using validated scales and secondary outcomes of adverse events, serious adverse events and QoL. We calculated the risk ratio with 95% confidence intervals (CIs) between groups for dichotomous outcomes. We measured arithmetic mean and standard deviation, and reported the mean difference (MD) with 95% CI between groups for continuous outcomes. We used standardised mean difference (SMD) with 95% CIs when an outcome was measured with different instruments measuring the same construct. We used a random-effects model to meta-analyse the outcome data. We rated the certainty of the evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies with 297 enroled participants; data were available for only 239 participants. Three studies compared corticosteroid (equivalent ≤ 8 mg dexamethasone) to placebo. One study compared corticosteroid (dexamethasone 4 mg) to an active comparator (modafinil 100 mg). There were insufficient data to evaluate subgroups, such as dose and duration of treatment. One study had a high risk of performance and detection bias due to lack of blinding, and one study had a high risk of attrition bias. Otherwise, we assessed risks of bias as low or unclear. Comparison 1: corticosteroids compared with placebo Participant-reported fatigue relief The was no clear difference between corticosteroids and placebo (SMD -0.46, 95% CI -1.07 to 0.14; 3 RCTs, 165 participants, very low-certainty evidence) for relief of fatigue at one week of the intervention. We downgraded the certainty of the evidence three times for study limitations due to unclear risk of bias, imprecision, and inconsistency. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (3 RCTs, 165 participants; very low-certainty evidence). Serious adverse events There was no clear difference in the occurrence of serious adverse events between groups, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Quality of lIfe One study reported QoL at one week using the Edmonton Symptom Assessment System (ESAS) well-being, and found no clear difference in QoL between groups (MD -0.58, 95% CI -1.93 to 0.77). Another study measured QoL using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QoL-ACD), and found no clear difference between groups. There was no clear difference between groups for either study, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Comparison 2: corticosteroids compared with active comparator (modafinil) Participant-reported fatigue relief There was improvement in fatigue from baseline to two weeks in both groups (modafinil MD 10.15, 95% CI 7.43 to 12.87; dexamethasone MD 9.21, 95% CI 6.73 to 11.69), however no clear difference between the two groups (MD -0.94, 95% CI -4.49 to 2.61; 1 RCT, 73 participants, very low-certainty evidence). We downgraded the certainty of the evidence three times for very serious study limitations and imprecision. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (1 RCT, 73 participants; very low-certainty evidence). Serious adverse events There were no serious adverse events reported in either group (1 RCT, 73 participants; very low-certainty evidence). Quality of lIfe One study measured QoL at two weeks, using the ESAS-well-being. There was marked improvement in QoL from baseline in both groups (modafinil MD -2.43, 95% CI -2.88 to -1.98; dexamethasone MD -2.16, 95% CI -2.68 to -1.64), however no clear difference between the two groups (MD 0.27, 95% CI -0.39 to 0.93; 1 RCT, 73 participants, very low-certainty evidence).
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF. We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF. Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.
Topics: Humans; Adult; Adolescent; Quality of Life; Modafinil; Adrenal Cortex Hormones; Neoplasms; Dexamethasone; Fatigue
PubMed: 36688471
DOI: 10.1002/14651858.CD013782.pub2 -
Arhiv Za Higijenu Rada I Toksikologiju Sep 2019An increasing number of people, students in particular, seek substances that improve their cognitive functioning. The most popular group of pharmacological cognitive... (Review)
Review
An increasing number of people, students in particular, seek substances that improve their cognitive functioning. The most popular group of pharmacological cognitive enhancers (PCEs) are stimulants. Available studies suggest a small beneficial effect of methylphenidate and amphetamine on memory, executive functions, and processing speed. However small, this effect can make the difference between success and failure. In recent years, research has focused on the additional beneficial effect on the emotional state, increased motivation, and placebo-induced cognitive enhancement. This paper briefly reviews the latest and most important research on the relationship between popular stimulants and cognitive enhancement. One cannot understand this relationship without understanding the Yerkes-Dodson law, which explains the relationship between the degree of arousal and performance. It suggests that the effect of stimulants is a dose-dependent continuum. This law has repeatedly been confirmed by studies in which an optimal level of psychoactivation for cognitive enhancement was obtained with low stimulant doses, whereas exceeding the effective dose resulted in cognitive deficits, psychomotor agitation, and addiction. A separate section has been devoted to modafinil, an increasingly popular stimulant that differs from the rest in neurochemical profile and behavioural effects.
Topics: Adult; Aged; Aged, 80 and over; Central Nervous System Stimulants; Cognition; Cognition Disorders; Female; Humans; Male; Methylphenidate; Middle Aged; Modafinil; Nootropic Agents; Psychotropic Drugs; Young Adult
PubMed: 32597132
DOI: 10.2478/aiht-2019-70-3298 -
Acta Neurologica Scandinavica Feb 2022To describe the pharmacological treatments (2005-2017) and the healthcare utilization (1997-2016) for patients with narcolepsy in Sweden in order to create a framework... (Observational Study)
Observational Study
OBJECTIVES
To describe the pharmacological treatments (2005-2017) and the healthcare utilization (1997-2016) for patients with narcolepsy in Sweden in order to create a framework for future organizational and economic analyses.
MATERIAL & METHODS
Patients of all ages with a diagnosis of narcolepsy registered in the National Patient Registry in specialist care in Sweden were included and information on treatments for narcolepsy was retrieved from The Swedish Prescribed Drug Register.
RESULTS
We collected 2508 patients with narcolepsy, 43,3% men and 56,7% women and 47,9% were prescribed modafenil, 33,8% metylphenidate and 26,2% amphetamine. In total, 3817 treatments were initiated. Patients treated with amphetamine had a higher mean age. More women than men used modafinil, methylphenidate, amphetamine and antidepressants. The narcolepsy population had more outpatient than inpatient healthcare. Patients treated with sodium oxybate had more outpatient visits than other narcolepsy patients, before and during treatment (p = .00).
CONCLUSIONS
This study gives valuable information on pharmaceutical treatments and healthcare utilization for patients with narcolepsy and can be used to estimate the healthcare cost in the future. Patients with sodium oxybate treatment had more outpatient visits than other patients before and during treatment which may be due to the need to monitor potentially severe side-effects or may indicate that patients with sodium oxybate treatment have a severe disease. The number of included patients was less than expected; however, this may depend on patients escaping our collection of data, which does not contain information from primary care.
Topics: Antidepressive Agents; Female; Humans; Male; Modafinil; Narcolepsy; Sodium Oxybate; Sweden
PubMed: 34611886
DOI: 10.1111/ane.13532 -
Diabetes Aug 2023
Topics: Mice; Male; Animals; Modafinil; Orexins; Hypoglycemia; Glucose; Neurons
PubMed: 37471600
DOI: 10.2337/dbi22-0038 -
Journal of the National Cancer Institute Aug 2014Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute... (Review)
Review
Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes.
Topics: Adolescent; Adult; Age Factors; Antimetabolites, Antineoplastic; Attention; Benzhydryl Compounds; Brain Neoplasms; Central Nervous System Stimulants; Child; Child, Preschool; Cognitive Dysfunction; Comorbidity; Cranial Irradiation; Donepezil; Early Intervention, Educational; Education, Special; Head and Neck Neoplasms; Human Growth Hormone; Humans; Indans; Infant; Injections, Spinal; Memory, Short-Term; Methotrexate; Methylphenidate; Modafinil; Neoplasms; Neurosurgical Procedures; Nootropic Agents; Patient Education as Topic; Piperidines; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Psychomotor Performance; Quality of Life; Radiotherapy Dosage; Risk Factors; Severity of Illness Index; Sex Factors; Survivors; Thinking; Wakefulness-Promoting Agents; Young Adult
PubMed: 25080574
DOI: 10.1093/jnci/dju186 -
The Cochrane Database of Systematic... Apr 2016Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of... (Review)
Review
BACKGROUND
Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and high levels of fatigue.
SEARCH METHODS
In March 2016, we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO and CINAHL and checked the reference lists of included studies. We also searched relevant conference proceedings, searched for ongoing trials via ClinicalTrials.gov and contacted major co-operative groups with trials in this area.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue.
DATA COLLECTION AND ANALYSIS
Three review authors (JD, SYK, DC) independently evaluated search results, extracted data from selected studies and carried out a bias risk assessment. We extracted data on fatigue, cognition, mood, quality of life and adverse events outcomes.
MAIN RESULTS
We identified nine studies. We excluded eight of these as they did not restrict participation to people with high fatigue. The single eligible trial investigated the use of modafinil compared to placebo. Although this study found a significant improvement over time in the primary outcome of fatigue, the improvement occurred after both modafinil and placebo with no significant difference in response between the two groups. The included trial did not reach its planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. The trial was at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation because the investigators did not analyse the impact of imputation on the results.
AUTHORS' CONCLUSIONS
There was insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
Topics: Adult; Benzhydryl Compounds; Brain Neoplasms; Fatigue; Humans; Modafinil; Randomized Controlled Trials as Topic; Wakefulness-Promoting Agents
PubMed: 27074263
DOI: 10.1002/14651858.CD011376.pub2 -
Sleep Dec 2014Forty-one percent of shift workers report dozing while driving. This study tested whether armodafinil improves driving simulator performance in subjects with shift work... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
Forty-one percent of shift workers report dozing while driving. This study tested whether armodafinil improves driving simulator performance in subjects with shift work disorder (SWD). A primary outcome was performance late in the shift when workers are typically driving home.
DESIGN
Randomized, double-blind, crossover. During each 12-h test session (21:30-09:30), subjects were kept awake except for multiple sleep latency testing (MSLT: 01:30, 03:30, 05:30, and 07:30). Subjective sleepiness (Karolinska Sleepiness Scale, KSS), driving performance, and cognitive performance (digit symbol substitution test and creativity on the Remote Associates Test, RAT) were evaluated during the night shift and commute home times.
SETTING
Hospital-based sleep research laboratory.
PARTICIPANTS
Twenty night workers (age: 42.7 ± 8.7 y, 17 F) with excessive sleepiness (≥ 10 on the Epworth Sleepiness Scale), meeting International Classification of Sleep Disorders, Second Edition (ICSD-2) criteria for SWD, and having no other medical conditions.
INTERVENTIONS
Armodafinil (150 mg) or placebo at (23:45 h) on counterbalanced nights separated by 7-14 days.
MEASUREMENT AND RESULTS
Primary endpoints were driving simulator performance (standard deviation of lateral position (SDLP) and off-road deviations) with four sessions starting 3.25 h after drug administration, objective sleepiness (MSLT; 1.75 to 7.75 h post-drug), and creativity (5 h post-drug). Significant effects of drug were observed for each driving measure (P < 0.05). Armodafinil significantly improved SDLP for simulator sessions at 05:30, 07:30, and 09:30, and off-road deviations at 7 h, 15 min and 9 h, 15 min post-drug (P < 0.05). Armodafinil also improved objective sleepiness from 3.7 ± 0.6 min to 9.7 ± 5.2 min (P < 0.001) and RAT score from 8.75 ± 4.9 to 11.25 ± 6.0 (P < 0.005).
CONCLUSIONS
Armodafinil 150 mg early in the night shift improves driving simulator performance in SWD. Effects on sleepiness, cognition, and driving were found up to 9.5 h post-ingestion, during the critical time when many night workers are driving home.
Topics: Adult; Attention; Automobile Driving; Benzhydryl Compounds; Cognition; Creativity; Cross-Over Studies; Disorders of Excessive Somnolence; Double-Blind Method; Female; Humans; Male; Middle Aged; Modafinil; Motor Skills; Sleep Disorders, Circadian Rhythm; Sleep Stages; Wakefulness; Wakefulness-Promoting Agents
PubMed: 25325498
DOI: 10.5665/sleep.4256