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Diagnostics (Basel, Switzerland) Dec 2021Sleep disorders are among the main comorbidities in patients with a Disorder of Consciousness (DOC). Given the key role of sleep in neural and cognitive functioning,... (Review)
Review
Sleep disorders are among the main comorbidities in patients with a Disorder of Consciousness (DOC). Given the key role of sleep in neural and cognitive functioning, detecting and treating sleep disorders in DOCs might be an effective therapeutic strategy to boost consciousness recovery and levels of awareness. To date, no systematic reviews have been conducted that explore the effect of sleep treatments in DOCs; thus, we systematically reviewed the existing studies on both pharmacological and non-pharmacological treatments for sleep disorders in DOCs. Among 2267 assessed articles, only 7 were included in the systematic review. The studies focused on two sleep disorder categories (sleep-related breathing disorders and circadian rhythm dysregulation) treated with both pharmacological (Modafinil and Intrathecal Baclofen) and non-pharmacological (positive airway pressure, bright light stimulation, and central thalamic deep brain stimulation) interventions. Although the limited number of studies and their heterogeneity do not allow generalized conclusions, all the studies highlighted the effectiveness of treatments on both sleep disorders and levels of awareness. For this reason, clinical and diagnostic evaluations able to detect sleep disorders in DOC patients should be adopted in the clinical routine for the purpose of intervening promptly with the most appropriate treatment.
PubMed: 35054255
DOI: 10.3390/diagnostics12010088 -
ACS Pharmacology & Translational Science Oct 2023Chronic stressful situations result in altered monoaminergic activity of neurotransmitters, resulting in various conditions characterized by deficits in learning, memory...
PURPOSE
Chronic stressful situations result in altered monoaminergic activity of neurotransmitters, resulting in various conditions characterized by deficits in learning, memory and attention. Stimulant effects can be visualized in terms of increased cognitive abilities through enhancement of dopamine (DA) release.
METHOD
This study examined cognitive responses and brain DA and 5-hydroxytryptamine (5HT) levels after prolonged methylphenidate (MPH) and modafinil administration, to demonstrate their effect on stress-induced cognitive deficits in rats. Effects on cognition were evaluated by passive avoidance and water maze tests. Furthermore brain levels of DA, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 5HT and 5-hydroxyindoleacetic acid (5HIAA) were analyzed by high-performance liquid chromatography coupled with electrochemical detection.
RESULTS
We found that both MPH and modafinil improved cognition in both restrained and unrestrained rats, as examined through water maze and passive avoidance tests. Furthermore, these substance were associated with increased brain DA and 5-HT levels. Notabily, we observed decrease in DOPAC and HVA levels, while 5-HIAA levels exhibited a slight increase.
CONCLUSIONS
The prevention of stress-induced cognitive deficits by MPH and modafinil could be elucidated through the interaction between 5HT and DA in regulating cognitive function.
PubMed: 37854618
DOI: 10.1021/acsptsci.3c00077 -
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 -
Purinergic Signalling Nov 2023Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression...
Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression contributes to the development of fibrotic diseases and whether AAR and AAR upregulation inhibits fibrotic responses. Primary human lung fibroblasts (HLFs) from normal (NHLFs) or patients with idiopathic pulmonary fibrosis (DHLF) were used for in vitro testing. Murine models of fibrotic liver or pulmonary disease were developed by injecting thioacetamide intraperitoneally, by feeding a high-fat diet, or by intratracheal instillation of bleomycin. Modafinil, which activates cAMP signaling via AAR and AAR, was administered orally. The protein amounts of AAR, AAR, and exchange protein directly activated by cAMP (Epac) were reduced, while collagen and α-smooth muscle actin (α-SMA) were elevated in DHLFs compared to NHLFs. In liver or lung tissue from murine models of fibrotic diseases, AAR and AAR were downregulated, but AAR and AAR were not. Epac amounts decreased, and amounts of collagen, α-SMA, K2.3, and K3.1 increased compared to the control. Modafinil restored the amounts of AAR, AAR, and Epac, and reduced collagen, α-SMA, K2.3, and K3.1 in murine models of fibrotic diseases. Transforming growth factor-β reduced the amounts of AAR, AAR, and Epac, and elevated collagen, α-SMA, K2.3, and K3.1 in NHLFs; however, these alterations were inhibited by modafinil. Our investigation revealed that AAR and AAR downregulation induced liver and lung fibrotic diseases while upregulation attenuated fibrotic responses, suggesting that AAR and AAR-upregulating agents, such as modafinil, may serve as novel therapies for fibrotic diseases.
PubMed: 37938538
DOI: 10.1007/s11302-023-09973-8 -
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 -
PloS One 2023Methamphetamine use and related harms have risen at alarming rates. While several psychosocial and pharmacologic interventions have been described in the literature,... (Review)
Review
RATIONALE
Methamphetamine use and related harms have risen at alarming rates. While several psychosocial and pharmacologic interventions have been described in the literature, there is uncertainty regarding the best approach for the management of methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU). We conducted a scoping review of recent systematic reviews (SR), clinical practice guidelines (CPG), and primary controlled studies of psychosocial and pharmacologic treatments for MUD/PMU.
METHODS
Guided by an a priori protocol, electronic database search updates (e.g., MEDLINE, Embase) were performed in February 2022. Screening was performed following a two-stage process, leveraging artificial intelligence to increase efficiency of title and abstract screening. Studies involving individuals who use methamphetamine, including key subgroups (e.g. those with mental health comorbidities; adolescents/youths; gay, bisexual, and other men who have sex with men) were sought. We examined evidence related to methamphetamine use, relapse, use of other substances, risk behaviors, mental health, harms, and retention. Figures, tables and descriptive synthesis were used to present findings from the identified literature.
RESULTS
We identified 2 SRs, one CPG, and 54 primary studies reported in 69 publications that met our eligibility criteria. Amongst SRs, one concluded that psychostimulants had no effect on methamphetamine abstinence or treatment retention while the other reported no effect of topiramate on cravings. The CPG strongly recommended psychosocial interventions as well as self-help and family support groups for post-acute management of methamphetamine-related disorders. Amongst primary studies, many interventions were assessed by only single studies; contingency management was the therapy most commonly associated with evidence of potential effectiveness, while bupropion and modafinil were analogously the most common pharmacologic interventions. Nearly all interventions showed signs of potential benefit on at least one methamphetamine-related outcome measure.
DISCUSSION
This scoping review provides an overview of available interventions for the treatment of MUD/PMU. As most interventions were reported by a single study, the effectiveness of available interventions remains uncertain. Primary studies with longer durations of treatment and follow-up, larger sample sizes, and of special populations are required for conclusive recommendations of best approaches for the treatment of MUD/PMU.
Topics: Male; Adolescent; Humans; Methamphetamine; Homosexuality, Male; Sexual and Gender Minorities; Artificial Intelligence; Central Nervous System Stimulants
PubMed: 37819931
DOI: 10.1371/journal.pone.0292745 -
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 -
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 -
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