-
International Journal of Stroke :... Oct 2023
Topics: Humans; Stroke; Fatigue; Quality of Life
PubMed: 37898830
DOI: 10.1177/17474930231207695 -
Revue Neurologique Oct 2023Idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS) are rare disorders of central hypersomnolence of unknown cause, affecting young people. However, increased... (Review)
Review
Idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS) are rare disorders of central hypersomnolence of unknown cause, affecting young people. However, increased sleep time and excessive daytime sleepiness (EDS) occur daily for years in IH, whereas they occur as relapsing/remitting episodes associated with cognitive and behavioural disturbances in KLS. Idiopathic hypersomnia is characterized by EDS, prolonged, unrefreshing sleep at night and during naps, and frequent morning sleep inertia, but rare sleep attacks, no cataplexy and sleep onset in REM periods as in narcolepsy. The diagnosis requires: (i) ruling out common causes of hypersomnolence, including mostly sleep apnea, insufficient sleep syndrome, psychiatric hypersomnia and narcolepsy; and (ii) obtaining objective EDS measures (mean latency at the multiple sleep latency test≤8min) or increased sleep time (sleep time>11h during a 18-24h bed rest). Treatment is similar to narcolepsy (except for preventive naps), including adapted work schedules, and off label use (after agreement from reference/competence centres) of modafinil, sodium oxybate, pitolisant, methylphenidate and solriamfetol. The diagnosis of KLS requires: (i) a reliable history of distinct episodes of one to several weeks; (ii) episodes contain severe hypersomnia (sleep>15h/d) associated with cognitive impairment (mental confusion and slowness, amnesia), derealisation, major apathy or disinhibited behaviour (hypersexuality, megaphagia, rudeness); and (iii) return to baseline sleep, cognition, behaviour and mood after episodes. EEG may contain slow rhythms during episodes, and rules out epilepsy. Functional brain imaging indicates hypoactivity of posterior associative cortex and hippocampus during symptomatic and asymptomatic periods. KLS attenuates with time when starting during teenage, including less frequent and less severe episodes. Adequate sleep habits, avoidance of alcohol and infections, as well as lithium and sometimes valproate (off label, after agreement from reference centres) help reducing the frequency and severity of episodes, and IV methylprednisolone helps reducing long (>30d) episode duration.
Topics: Adolescent; Humans; Kleine-Levin Syndrome; Idiopathic Hypersomnia; Disorders of Excessive Somnolence; Sleep; Narcolepsy
PubMed: 37684104
DOI: 10.1016/j.neurol.2023.08.010 -
Current Opinion in Chemical Biology Oct 2023In the review, current status of sulfoxides on the pharmaceutical market is discussed. In the first part of the article, natural sulfoxides will be described with a... (Review)
Review
In the review, current status of sulfoxides on the pharmaceutical market is discussed. In the first part of the article, natural sulfoxides will be described with a special focus on sulforaphane and amanitin, a mushroom toxin which has been developed as payload in antibody drug conjugates in the possible cancer treatment. Controversies associated with the medical use of dimethylsulfoxide are briefly described in the next section. In the part devoted to PPIs, the benefits of using pure enantiomers (chiral switch) are discussed. An interesting approach, repositioning of drugs is exemplified by new possible applications of modafinil and sulindac. The review is concluded by presentation of cenicriviroc and adezmapimod, both with the status of promising drug candidates.
Topics: Sulfoxides; Dimethyl Sulfoxide; Stereoisomerism
PubMed: 37307682
DOI: 10.1016/j.cbpa.2023.102340 -
Annals of Clinical Psychiatry :... Aug 2023Bipolar depression is a serious neuropsychiatric disorder associated with a high risk of morbidity and suicidality. Standard antidepressants approved for treating major...
BACKGROUND
Bipolar depression is a serious neuropsychiatric disorder associated with a high risk of morbidity and suicidality. Standard antidepressants approved for treating major depressive disorder fail to exert efficacy in bipolar depression. Although 5 agents have been developed for the treatment of bipolar depression, treatment resistance is still observed in some patients, and requires off-label pharmacotherapy. Modafinil and armodafinil have been reported to improve treatment-resistant bipolar depression, but with inconsistent results.
METHODS
We present a case of a 65-year-old woman with severe bipolar depression who failed to respond to electroconvulsive therapy and IV ketamine but later responded to high-dose armodafanil.
RESULTS
The patient responded to high-dose armodafinil (gradually titrated to 1,000 mg/d) and achieved remission with good tolerability for 5 years. Recently, she contracted COVID-19 and developed muscular weakness. After a lengthy workup, we became concerned for myopathy as an adverse effect from armodafinil. The patient's dose of armodafinil was significantly reduced and she subsequently became very depressed and functionally disabled before improving again when armodafinil 1,000 mg/d was reinstated.
CONCLUSIONS
We propose that some of the negative results seen in research of armodafinil for bipolar depression may be due to the use of low doses (100 to 200 mg/d), and higher doses may be needed for adequate response in treatment-resistant bipolar depression.
Topics: Female; Humans; Aged; Modafinil; Bipolar Disorder; Depressive Disorder, Major; Benzhydryl Compounds; COVID-19
PubMed: 37459498
DOI: 10.12788/acp.0113 -
Frontiers in Pharmacology 2024Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that... (Review)
Review
Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that the neural circuits underlying the regulation and expression of social behaviors are highly overlapped with those targeted by psychostimulants, which in most cases have strong rewarding and, consequently, addictive properties. In the present work, we provide an overview regarding the effects of illicit and prescription psychostimulants, such as cocaine, amphetamine-type stimulants, methylphenidate or modafinil, upon social behaviors such as social play, maternal behavior, aggression, pair bonding and social cognition and how psychostimulants in both animals and humans alter them. Finally, we discuss why these effects can vary depending on numerous variables such as the type of drug considered, acute long-term use, clinical recreational consumption, or the presence or absence of concomitant risk factors.
PubMed: 38725665
DOI: 10.3389/fphar.2024.1364630 -
Journal of Clinical Sleep Medicine :... Mar 2024This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical...
UNLABELLED
This case report recounts the details of a patient diagnosed with narcolepsy and cataplexy whose headaches improved once treatment with armodafinil began. The clinical significance of this report lies in the fact that armodafinil is known to cause headaches, at least initially. But perhaps through a reduced need for caffeine and/or a regulation of sleep/wake, armodafinil may reduce headache frequency and severity.
CITATION
Barone DA. Headache improves with armodafinil. 2024;20(3):469-470.
Topics: Humans; Modafinil; Narcolepsy; Caffeine; Cataplexy; Headache
PubMed: 37921201
DOI: 10.5664/jcsm.10906 -
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 -
Advances in Pharmacology (San Diego,... 2024Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has...
Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an "atypical" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.
Topics: Humans; Modafinil; Central Nervous System Stimulants; Benzhydryl Compounds; Dopamine; Substance-Related Disorders
PubMed: 38467484
DOI: 10.1016/bs.apha.2023.10.006