-
CNS Drugs Feb 2020Pitolisant (Wakix), an orally available, first-in-class antagonist/inverse agonist of the histamine 3 receptor, is approved in the EU (as of March 2016) for the... (Review)
Review
Pitolisant (Wakix), an orally available, first-in-class antagonist/inverse agonist of the histamine 3 receptor, is approved in the EU (as of March 2016) for the treatment of narcolepsy with or without cataplexy in adults and in the USA (as of August 2019) for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy. Pitolisant was demonstrated to have minimal risk of abuse in preclinical and clinical studies, and is the only anti-narcoleptic drug not scheduled as a controlled substance in the USA. The totality of evidence from pivotal and supportive phase III trials suggests that pitolisant administered at up to the recommended maximum dose of 36 mg once daily reduces EDS and cataplexy in adults with narcolepsy relative to placebo. Noninferiority of pitolisant to modafinil in the management of EDS was not demonstrated. Pitolisant was generally well tolerated in clinical trials. Consistent with its mechanism of action, the most common treatment-emergent adverse events included headache, insomnia and anxiety. With minimal abuse potential and offering the convenience of oral, once-daily administration, pitolisant extends the range of approved treatment options available to adult patients with narcolepsy with or without cataplexy.
Topics: Animals; Cataplexy; Clinical Trials, Phase III as Topic; Humans; Narcolepsy; Piperidines
PubMed: 31997137
DOI: 10.1007/s40263-020-00703-x -
Journal of Sleep Research Oct 2023The orexin 2 receptor-selective agonist danavorexton (TAK-925) has been shown to produce wake-promoting effects in wild-type mice, narcolepsy-model mice, and individuals... (Randomized Controlled Trial)
Randomized Controlled Trial
The orexin 2 receptor-selective agonist danavorexton (TAK-925) has been shown to produce wake-promoting effects in wild-type mice, narcolepsy-model mice, and individuals with narcolepsy type 1 and type 2. Here, we report wake-promoting effects of danavorexton in non-human primates and healthy men during their sleep phase. Electroencephalogram analyses revealed that subcutaneous administration of danavorexton significantly increased wakefulness in common marmosets (p < 0.05 at 0.1 mg kg , and p < 0.001 at 1 mg kg and 10 mg kg ) and cynomolgus monkeys (p ≤ 0.05 at 1 mg kg and 3 mg kg ). In a phase 1b crossover, randomized, double-blind, placebo-controlled and active-controlled study in sleep-deprived healthy participants (ClinicalTrials.gov identifier: NCT03522506), modafinil 300 mg (used to demonstrate assay sensitivity) and continuous infusion of danavorexton 44 mg and danavorexton 112 mg showed statistically superior wake-promoting effects to placebo (n = 18). Measured using the Maintenance of Wakefulness Test, mean (standard deviation) sleep latencies during infusion of danavorexton 44 mg, danavorexton 112 mg and placebo were 21.4 (8.9), 31.8 (3.2) and 9.2 (6.4) min, respectively. Least-squares mean difference from placebo in average sleep latency was 16.8 min with danavorexton 44 mg and 30.2 min with danavorexton 112 mg (both p < 0.001). Karolinska Sleepiness Scale scores were statistically significantly lower (indicating decreased sleepiness) for participants receiving danavorexton than for those receiving placebo during infusion (danavorexton 44 mg, p = 0.010; danavorexton 112 mg, p < 0.001). Together, these results indicate that an orexin 2 receptor agonist increases wakefulness in non-human primates and healthy individuals during their sleep phase.
Topics: Animals; Double-Blind Method; Narcolepsy; Orexins; Primates; Sleepiness; Treatment Outcome; Wakefulness; Humans; Male
PubMed: 36934366
DOI: 10.1111/jsr.13878 -
The International Journal on Drug Policy Sep 2021Unregulated use of pharmaceuticals for cognitive enhancement has become a topic of growing concern, as recent studies indicate a growing prevalence in several countries....
BACKGROUND
Unregulated use of pharmaceuticals for cognitive enhancement has become a topic of growing concern, as recent studies indicate a growing prevalence in several countries. Prescription stimulants, also termed Study drugs (SDs) are typically accessed through peers but new studies show that social media platforms may play an important role in the diffusion of these pharmaceuticals. While there is scholarly focus on supply and purchasing practices, other aspects of drugs on social media have received less attention. The aim of this article is to show how SDs are portrayed on Instagram and to discuss some of the implications.
METHODS
To find and collect Instagram posts related to SDs we conducted hashtag searches with a number of relevant terms; #studydrugs, #nootropics, #cognitiveenhancers, #smartdrugs, and #modafinil. A total of 563 posts including a selection of post comments, were included in the study and analyzed using the Content Analysis method.
RESULTS
SD-related posts can be categorized into four main types; sales advertisement, personal experience, public information, and motivational quotes. Regardless of its kind, the majority of posts mainly express a positive sentiment towards SDs and SD use. Comments below posts show that people are influenced by SD-related posts and use Instagram for a variety of reasons in relation to their own SD praxis CONCLUSION: This study reveals that Instagram is used to facilitate not only access to SDs, but also a great deal of communication that generally seeks to motivate, promote or encourage the use of pharmaceuticals for enhancement. The positive sentiment towards SDs may play an important role as it provides a false sense of security to current and potential users by posting content that portrays this kind of drug use as the easy and safe solution to social and personal pressures of becoming a successful individual.
Topics: Communication; Humans; Motivation; Social Media
PubMed: 33451861
DOI: 10.1016/j.drugpo.2020.103100 -
Sleep Jun 2021Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have... (Review)
Review
Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have been on a rapid rise, with growing detrimental effects on mental and physical health, and devastating psychosocial impact pressing for intervention. Among the unwanted effects of methamphetamine, acute and long-term sleep impairments are of major concern, posing a significant therapeutic challenge, and a cause of addiction relapse. Unraveling mechanisms and functional correlates of methamphetamine-related sleep and circadian disruption are, therefore, of key relevance to translational and clinical psychiatry. In this article, we review the mounting evidence for the acute and long-term impairements of sleep-wake behavior and circadian activity caused by single or recurring methamphetamine usage and withdrawal. Factors contributing to the severity of sleep loss and related cognitive deficit, with risks of relapse are discussed. Key molecular players mediating methamphetamine-induced dopamine release and neuromodulation are considered, with wake-promoting effects in mesolimbic circuits. The effects on various sleep phases and related changes in dopamine levels in selected subcortical structures are reviewed and compared to other psychostimulants with similar action mechanisms. A critical appraisal is presented of the therapeutic use of modafinil, countering sleep, and circadian rhythm impairments. Finally, emerging knowledge gaps and methodical limitations are highlighted along with the areas for future research and therapeutic translation.
Topics: Central Nervous System Stimulants; Dopamine; Methamphetamine; Modafinil; Sleep
PubMed: 33406259
DOI: 10.1093/sleep/zsab001 -
Acta Neuropsychiatrica Aug 2023Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect... (Review)
Review
OBJECTIVES
Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect treatment outcomes adversely. We aimed to review all relevant previous reports.
METHODS
We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI).
RESULTS
According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants - usually SSRIs - can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate-modafinil-olanzapine combination.
CONCLUSION
Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition.
Topics: Selective Serotonin Reuptake Inhibitors; Apathy; Olanzapine; Antidepressive Agents; Bupropion
PubMed: 36644883
DOI: 10.1017/neu.2023.6 -
JAMA Oncology Feb 2022Nearly 96% of patients with high-grade glioma (HGG) report moderate-to-severe fatigue. Armodafinil is a psychostimulant that might help cancer-related fatigue in... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Nearly 96% of patients with high-grade glioma (HGG) report moderate-to-severe fatigue. Armodafinil is a psychostimulant that might help cancer-related fatigue in patients with HGG.
OBJECTIVE
To determine whether armodafinil reduces fatigue in patients with HGG and moderate-to-severe fatigue.
DESIGN, SETTING, AND PARTICIPANTS
In this randomized multicenter, phase 3, double-blinded, placebo-controlled clinical trial, adults with HGG and moderate-to-severe fatigue who were clinically stable at least 4 weeks after completing radiation therapy were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo over 8 weeks. A score of at least 6 out of 10 on severity scale for the brief fatigue inventory scale, with 10 being the worst, was required to suggest moderate-to-severe fatigue. Patients were allowed stable doses of corticosteroids but were excluded if they required increasing amounts of corticosteroids, were receiving some other treatment for fatigue, or had an uncontrolled seizure disorder. The study was conducted from June 2013 to December 15, 2019.
INTERVENTIONS
Patients were randomized to 150 mg of armodafinil, 250 mg of armodafinil, or placebo for a total of 8 weeks with assessments at weeks 4 and 8.
MAIN OUTCOMES AND MEASURES
The primary outcome was efficacy in treating cancer-related fatigue. Secondary outcomes included safety, neurocognitive function, and quality of life. Patients were evaluated at baseline and at weeks 4 and 8. Efficacy between the placebo and the 2 doses of study drug was determined by an improvement by 2 points on the 0 to 10 brief fatigue inventory scale. Kruskal-Wallis and χ2 tests were used and followed by confirmatory analyses.
RESULTS
A total of 328 patients were enrolled, of whom 297 had evaluable end point data. Of these, 103 received 150 mg of armodafinil (mean [SD] age, 58.5 [11.9] years; 42 women [40.8%]), 97 250 mg of armodafinil (mean [SD] age, 56.6 [12.5] years; 37 women [38.1%]), and 97 placebo (mean [SD] age, 57.1 [12.5] years; 39 women [40.2%]). There was no difference in the proportion of patients who achieved clinically meaningful fatigue reduction between arms (28% [95% CI 20%-30%] for 150 mg of armodafinil, 28% [95% CI 19%-38%] for 250 mg of armodafinil, and 30% [95% CI 21%-40%] for placebo). There was a statistically significant reduction in global fatigue for corticosteroid users compared with nonusers (-0.7 [95% CI, -1.5 to -0.3] vs -1.7 [95% CI, -2.1 to -1.3]; P < .001). More patients (2 vs 7) reported insomnia with treatment with 250 mg of armodafinil.
CONCLUSIONS AND RELEVANCE
The results of this randomized clinical trial found no meaningful benefit of using treatment with armodafinil to reduce cancer-related fatigue in patients with HGG.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01781468.
Topics: Adult; Aged; Benzhydryl Compounds; Double-Blind Method; Fatigue; Female; Glioma; Humans; Male; Middle Aged; Modafinil; Quality of Life; Treatment Outcome
PubMed: 34882169
DOI: 10.1001/jamaoncol.2021.5948 -
JAMA Internal Medicine Feb 2021This cohort study uses data from the US Provigil/Nuvigil Pregnancy Registry to assess prevalence of fetal major congenital malformations after exposure to modafinil and...
This cohort study uses data from the US Provigil/Nuvigil Pregnancy Registry to assess prevalence of fetal major congenital malformations after exposure to modafinil and armodafinil during pregnancy.
Topics: Abnormalities, Drug-Induced; Female; Humans; Modafinil; Narcolepsy; Pregnancy; Registries; United States; Wakefulness-Promoting Agents
PubMed: 33074297
DOI: 10.1001/jamainternmed.2020.4009 -
Expert Review of Neurotherapeutics Apr 2024Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment... (Review)
Review
INTRODUCTION
Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment options include psychological and pharmacological interventions.
AREAS COVERED
This narrative review explores existing pharmacological treatments for GD. The following classes of medications were considered: opioid-receptor antagonists (e.g. naltrexone and nalmefene), serotonin reuptake inhibitors (e.g. fluvoxamine, paroxetine, sertraline, escitalopram, and citalopram), glutamatergic agents (e.g. N-acetylcysteine (NAC), acamprosate, and memantine), mood stabilizers (e.g. topiramate, carbamazepine, lithium), and other medications (e.g. modafinil, nefazodone, olanzapine, haloperidol, tolcapone, and bupropion).
EXPERT OPINION
Due to the limitations of the studies reviewed, solid conclusions regarding the optimal choice of pharmacotherapy for individuals with GD are challenging to draw at this time. Despite some medications, such as naltrexone and nalmefene, showing promising results, efficacy has varied across studies. The review highlights current gaps/limitations, including small sample sizes, limited diversity in participant demographics, the need for exploring different gambling subtypes and treatment responses, high placebo response rates, lack of longer-term longitudinal information, limited investigation of neurobiological correlates and co-occurring disorders, and the importance of implementation research. Further research is needed to address these gaps and explore additional medications, as well as interventions like neuromodulation.
Topics: Humans; Gambling; Naltrexone; Behavior, Addictive; Narcotic Antagonists; Selective Serotonin Reuptake Inhibitors
PubMed: 38357896
DOI: 10.1080/14737175.2024.2316833 -
Cancer Medicine May 2023Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including... (Review)
Review
BACKGROUND
Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours.
METHODS
We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021.
RESULTS
In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention.
CONCLUSION
The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.
Topics: Adult; Humans; Quality of Life; Cognitive Dysfunction; Cognition; Cognition Disorders; Brain Neoplasms
PubMed: 36880363
DOI: 10.1002/cam4.5760 -
Epilepsy & Behavior : E&B Sep 2021Excessive daytime sleepiness (EDS) and attentional deficits are often observed in people with epilepsy. They may be the consequence of seizures and subclinical... (Review)
Review
Excessive daytime sleepiness (EDS) and attentional deficits are often observed in people with epilepsy. They may be the consequence of seizures and subclinical discharges as well as of comorbid conditions as obstructive sleep apnea/hypopnea syndrome (OSAS), attention deficit hyperactivity disorder (ADHD), or other less frequent disorders. Excessive daytime sleepiness may also be caused or worsened by antiseizure medications (ASMs). Several meta-analyses suggested that lamotrigine, lacosamide, and perhaps eslicarbazepine are less sedative than other traditional and new ASMs and, in patients prone to somnolence, might be preferred over ASMs with more sedative properties. In patients with severe EDS and/or ADHD, advantages and risks of a treatment with a psychostimulant need to be considered. Methylphenidate, modafinil, armodafinil, pitolisant, and solriamfetol are authorized for use in ADHD and EDS in patients with narcolepsy and some of them also in OSAS. These agents are off-label for the treatment of EDS associated with epilepsy. They do not have proconvulsant effects, although there are several possible risks for patients with epilepsy. The risks of cardiovascular events and psychiatric symptoms should be carefully evaluated as such disorders can coexist with epilepsy and be triggered by these agents. Finally, combination of psychostimulants with ASMs may be associated with several pharmacokinetic drug-drug interactions.
PubMed: 34534876
DOI: 10.1016/j.yebeh.2021.108311