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Frontiers in Pharmacology 2022Fibromyalgia is a chronic neurological condition characterized by widespread pain. The effectiveness of current pharmacological treatments is limited. However, several... (Review)
Review
Fibromyalgia is a chronic neurological condition characterized by widespread pain. The effectiveness of current pharmacological treatments is limited. However, several medications have been approved for phase IV trials in order to evaluate them. To identify and provide details of drugs that have been tested in completed phase IV clinical trials for fibromyalgia management in adults, including the primary endpoints and treatment outcomes. This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology. Publicly available and relevant phase IV trials registered at ClinicalTrials.gov were analyzed. The uses of the trialed drugs for fibromyalgia were reviewed. As of 8 August 2022, a total of 1,263 phase IV clinical trials were identified, of which 121 were related to fibromyalgia. From these, 10 clinical trials met the inclusion criteria for the current study. The drugs used in phase IV trials are milnacipran, duloxetine, pregabalin, a combination of tramadol and acetaminophen, and armodafinil. The effectiveness of the current pharmacological treatments is apparently limited. Due to its complexity and association with other functional pain syndromes, treatment options for fibromyalgia only are limited and they are designed to alleviate the symptoms rather than to alter the pathological pathway of the condition itself. Pain management specialists have numerous pharmacologic options available for the management of fibromyalgia.
PubMed: 36210856
DOI: 10.3389/fphar.2022.1017129 -
Iranian Journal of Child Neurology 2022Given the importance of having a continuous performance for the academic and social life of children with attention-deficit/hyperactivity disorder (ADHD), in this study,...
OBJECTIVES
Given the importance of having a continuous performance for the academic and social life of children with attention-deficit/hyperactivity disorder (ADHD), in this study, a Continuous Performance Test (CPT) was used to compare the effect of long-acting methylphenidate and modafinil on attention and impulsivity of these children.
MATERIALS & METHODS
A randomized clinical trial was conducted on 50 children with ADHD aged 6 to 12 years in the child and adolescent psychiatric departments of Imam Hossein and Mofid hospitals, Tehran, Iran. The children were selected by availability sampling and randomly assigned into two equal groups (n=25 in each). While the first group was treated with long-acting methylphenidate, the second was treated with modafinil for 14 days. The CPT was carried out before and after the treatment. The obtained data were analyzed by F and t tests.
RESULTS
Long-acting methylphenidate and modafinil were both effective in improving attention and impulsivity in children with ADHD. There was no significant difference between the two drugs in terms of effectiveness on attention and impulsivity.
CONCLUSION
The findings of this study showed that long-acting methylphenidate and modafinil are equally effective in improving attention and impulsivity in children with ADHD aged 6 to 12 years.
PubMed: 36204437
DOI: 10.22037/ijcn.v16i2.32541 -
Turk Psikiyatri Dergisi = Turkish... 2022Antidepressants are known to cause sexual dysfunctions. Sexual side effects due to antidepressants negatively affect compliance with treatment. Modafinil is a stimulant...
Antidepressants are known to cause sexual dysfunctions. Sexual side effects due to antidepressants negatively affect compliance with treatment. Modafinil is a stimulant drug used for narcolepsy and some other sleep disorders. It is also used in treatment of resistant depression, chronic fatigue syndrome, attention deficit hyperactivity disorder, and cocaine addiction syndrome. In this article, two female patients whose depressive complaints improved with antidepressant treatment, but who applied to the psychiatry outpatient clinic with complaints of sexual dysfunction and daytime sleepiness, will be presented. Both patients had loss of sexual desire, arousal and orgasm difficulties. The sexual histories obtained from the patients suggested that there was no sexual dysfunction in the period before they started using antidepressants. Both patients stated that they did not want to change the current antidepressant treatment. Modafinil 100 mg/day was prescribed to the patients for daytime sleepiness. One month after the initiation of modafinil 100 mg/day in the 39-yearold patient, there was a marked decrease in the complaints of loss of sexual desire, decreased sexual arousal and orgasm difficulties. In the other patient, 43 years old, a slight improvement in sexual functions was observed after the initiation of modafinil. In this case, after the modafinil dose was increased to 200 mg/day, there was a significant improvement in sexual dysfunctions. In both cases, the improvement in sexual dysfunctions and possible mechanisms as a result of the addition of modafinil to the treatment will be discussed. Keywords: Antidepressant, woman, sexual dysfunction, modafinil.
Topics: Adult; Antidepressive Agents; Benzhydryl Compounds; Central Nervous System Stimulants; Disorders of Excessive Somnolence; Female; Humans; Modafinil
PubMed: 36148571
DOI: 10.5080/u25974 -
Pharmaceuticals (Basel, Switzerland) Sep 2022Glutamate is an excitatory neurotransmitter in the nervous system. Excessive glutamate transmission can lead to increased calcium ion expression, related to increased...
Glutamate is an excitatory neurotransmitter in the nervous system. Excessive glutamate transmission can lead to increased calcium ion expression, related to increased neurotoxicity. Memantine is used for treating patients with Alzheimer's disease (AD) due to its protective action on the neurons against toxicity caused by over activation of N-methyl-D-aspartate receptors. Nootropics, also called "smart drugs", are used for the treatment of cognitive deficits. In this work, we evaluate the neuroprotective action of four memantine analogues of glycine derivatives, including glycyl-glycine, glycyl-glycyl-glycine, sarcosine, dimethylglycine and three conjugates with nootropics, modafinil, piracetam and picamilon. The new structural memantine derivatives improved cell viability against copper-induced neurotoxicity in APPswe cells and glutamate-induced neurotoxicity in SH-SY5Y cells. Among these novel compounds, modafinil-memantine, piracetam-memantine, sarcosine-memantine, dimethylglycine-memantine, and glycyl-glycine-memantine were demonstrated with good EC values of the protective effects on APPswe cells, accompanied with moderate amelioration from glutamate-induced neurotoxicity. In conclusion, our study demonstrated that novel structural derivatives of memantine might have the potential to develop promising lead compounds for the treatment of AD. The solubility of memantine analogues with nootropics and memantine analogues with glycine derivatives in buffer solutions at pH 2.0 and pH 7.4 simulating the biological media at 298.15 K was determined and the mutual influence of the structural fragments in the molecules on the solubility behavior was analyzed. The significative correlation equations relating the solubility and biological properties with the structural HYBOT (Hydrogen Bond Thermodynamics) descriptors were derived. These equations would greatly simplify the task of the directed design of the memantine analogues with improved solubility and enhanced bioavailability.
PubMed: 36145329
DOI: 10.3390/ph15091108 -
International Journal of Molecular... Sep 2022Attention deficit hyperactivity disorder (ADHD) is one of the most common worldwide mental disorders in children, young and adults. If left untreated, the disorder can...
Attention deficit hyperactivity disorder (ADHD) is one of the most common worldwide mental disorders in children, young and adults. If left untreated, the disorder can continue into adulthood. The abuse of ADHD-related drugs to improve mental performance for studying, working and everyday life is also rising. The potentially high number of subjects with controlled or uncontrolled use of such substances increases the impact of possible side effects. It has been shown before that the early ADHD drug methylphenidate influences bone metabolism negatively. This study focused on the influence of three more recent cognitive enhancers, modafinil, atomoxetine and guanfacine, on the differentiation of mesenchymal stem cells to osteoblasts and on their cell functions, including migration. Human mesenchymal stem cells (hMSCs) were incubated with a therapeutic plasma dosage of modafinil, atomoxetine and guanfacine. Gene expression analyses revealed a high beta-2 adrenoreceptor expression in hMSC, suggesting it as a possible pathway to stimulate action. In bone formation assays, all three cognitive enhancers caused a significant decrease in the mineralized matrix and an early slight reduction of cell viability without triggering apoptosis or necrosis. While there was no effect of the three substances on early differentiation, they showed differing effects on the expression of (), () and () in the later stages of osteoblast development, suggesting alternative modes of action. All three substances significantly inhibited hMSC migration. This effect could be rescued by a selective beta-blocker (Imperial Chemical Industries ICI-118,551) in modafinil and atomoxetine, suggesting mediation via beta-2 receptor stimulation. In conclusion, modafinil, atomoxetine and guanfacine negatively influence hMSC differentiation to bone-forming osteoblasts and cell migration through different intracellular pathways.
Topics: Adult; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Cell Differentiation; Central Nervous System Stimulants; Child; Guanfacine; Humans; Ligands; Methylphenidate; Modafinil; Nootropic Agents; Osteoprotegerin; Receptor Activator of Nuclear Factor-kappa B
PubMed: 36142172
DOI: 10.3390/ijms231810257 -
Pharmacology, Biochemistry, and Behavior Oct 2022Narcolepsy type 1 (NT1), caused by loss of orexin neurons, is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, disrupted nighttime...
Narcolepsy type 1 (NT1), caused by loss of orexin neurons, is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, hypnagogic/hypnopompic hallucinations and sleep paralysis, as well as a high risk of obesity. Danavorexton (TAK-925) is a novel brain-penetrant orexin 2 receptor (OX2R)-selective agonist currently being evaluated in clinical trials for the treatment of hypersomnia disorders including NT1. Thus, detailed characterization of danavorexton is critical for validating therapeutic potential of OX2R-selective agonists. Here, we report preclinical characteristics of danavorexton as a therapeutic drug for NT1. Danavorexton showed rapid association/dissociation kinetics to OX2R. The activation mode of endogenous OX2R by danavorexton and orexin peptide was very similar in an electrophysiological analysis. In orexin/ataxin-3 mice, a mouse model of NT1, danavorexton promoted wakefulness, and ameliorated fragmentation of wakefulness during the active phase after both acute and repeated administration, suggesting a low risk of receptor desensitization. Electroencephalogram (EEG) power spectral analysis revealed that danavorexton, but not modafinil, normalized dysregulated EEG power spectrum in orexin/ataxin-3 mice during the active phase. Finally, repeated administration of danavorexton significantly suppressed the body weight gain in orexin/ataxin-3 mice. Danavorexton may have the potential to treat multiple symptoms of NT1. These preclinical findings, together with upcoming clinical observations of danavorexton, could improve our understanding of the pathophysiology of NT1 and therapeutic potential of OX2R agonists.
Topics: Animals; Ataxin-3; Disease Models, Animal; Mice; Narcolepsy; Orexin Receptors; Orexins; Wakefulness
PubMed: 36108771
DOI: 10.1016/j.pbb.2022.173464 -
The Cochrane Database of Systematic... Sep 2022Fatigue 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. This is an updated version of the original Cochrane Review published in Issue 4, 2016.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.
SEARCH METHODS
For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.
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 to improve the clinical utility of the findings.
DATA COLLECTION AND ANALYSIS
Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.
MAIN RESULTS
The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.
AUTHORS' CONCLUSIONS
There is currently 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; Brain Neoplasms; Dextroamphetamine; Fatigue; Glioma; Humans; Modafinil
PubMed: 36094728
DOI: 10.1002/14651858.CD011376.pub3 -
JAAD Case Reports Sep 2022
PubMed: 36046806
DOI: 10.1016/j.jdcr.2022.07.024 -
Cureus Jul 2022Narcolepsy is a clinical syndrome of hypothalamic disorder characterized by several sleep-wake disorders. The most common features include daytime sleepiness associated...
Narcolepsy is a clinical syndrome of hypothalamic disorder characterized by several sleep-wake disorders. The most common features include daytime sleepiness associated with hallucinations (hypnagogic and hypnopompic hallucinations) at the transition time of sleep-wake time, cataplexy or sudden loss of muscle tone, and sleep paralysis. We present a case of a patient affected with both narcolepsy and postural orthostatic tachycardia syndrome (POTS). POTS is a rare disorder characterized by orthostatic intolerance and abnormal autonomic response while sustaining an upright posture. In this case report, we highlight the impact of POTS on the choice of pharmacotherapy for narcolepsy.
PubMed: 36043022
DOI: 10.7759/cureus.27287 -
Sleep and Biological Rhythms Oct 2022The objectives of this study were to describe prevalence, incidence, and medications among patients who were diagnosed with narcolepsy in Japan using a claims database....
UNLABELLED
The objectives of this study were to describe prevalence, incidence, and medications among patients who were diagnosed with narcolepsy in Japan using a claims database. Patients diagnosed with narcolepsy were identified from January 2010 to December 2019 using an employment-based health insurance claims database compiled by JMDC Inc. The prevalence and incidence of narcolepsy were estimated annually in the overall population and by age and sex among employees and their dependents aged < 75 years. Medications, examined for each quarter in the overall population, were modafinil, methylphenidate, pemoline, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors. We identified 1539 patients with narcolepsy. The overall annual prevalence increased from 5.7 to 18.5/100,000 persons in 2010 and 2019, respectively. Large increases were found from 2010 to 2019 in patients aged 20-29 years and 10-19 years, with the highest prevalence in 2019 (9.7-37.5/100,000 persons and 5.0-27.1/100,000 persons). The overall incidence slightly increased from 3.6 to 4.3/100,000 person-year from 2010 to 2019, and the highest incidence was found in patients aged 20-29 years and 10-19 years (5.8-11.3/100,000 person-year, and 3.8-7.4/100,000 person-year from 2010 to 2019, respectively). Methylphenidate and modafinil were commonly prescribed in 2010 (27.3-38.9% and 17.5-45.5%, respectively). Methylphenidate prescriptions declined during the 10 years, whereas modafinil prescriptions increased (15.6-17.1% and 43.8-45.8% in 2019, respectively). The estimated prevalence and incidence of narcolepsy appeared to increase from 2010 to 2019, especially in teenagers and 20-year olds.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s41105-022-00406-4.
PubMed: 38468628
DOI: 10.1007/s41105-022-00406-4