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Trials Apr 2024Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the...
5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.
BACKGROUND
Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer.
METHODS
The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups.
DISCUSSION
The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines.
TRIAL REGISTRATION
IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.
Topics: Adult; Humans; Amantadine; Bupropion; Fatigue; Methylphenidate; Multicenter Studies as Topic; Neoplasms; Panax; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38570861
DOI: 10.1186/s13063-024-08078-w -
Psychiatria Polska Dec 2023In this article, we present the case of an adult patient, whose main problem is episodes of fantasizing and rocking lasting up to 12 hours a day and completely...
In this article, we present the case of an adult patient, whose main problem is episodes of fantasizing and rocking lasting up to 12 hours a day and completely preventing school development. The nature of the disorder in the patient is related to the sinking into fantasies, and not typical obsessions as in OCD. The patient was previously treated with drugs from the SSRI group, neuroleptics (without aripiprazole) and methylphenidate. Only methylphenidate showed some improvement; however, it made the patient feel ‟stiff in thinking". The patient was hospitalized because of a suicide attempt, which, as it later turned out, was self-harm with no intention of killing himself. During hospitalization, a differential diagnosis was performed and the diagnosis of Asperger's syndrome was made, which was accompanied by immersion in the world of one's fantasies and stereotypical behavior. The patient was administered aripiprazole at a dose of 15 mg/d and after three weeks, a significant improvement in health was achieved, including a reduction in the duration of episodes from several hours to several dozen seconds. The drug is well tolerated by the patient. The patient was discharged from the hospital and continues his school education. In the article, we present single case reports in which similar spectacular results were achieved in similar cases. We also describe a possible physiological explanation for this response to this drug.
Topics: Adult; Humans; Asperger Syndrome; Aripiprazole; Antipsychotic Agents; Suicide, Attempted; Methylphenidate
PubMed: 38564518
DOI: 10.12740/PP/152316 -
MedRxiv : the Preprint Server For... Jun 2024Widely prescribed for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (e.g., methylphenidate) have been studied for their chronic effects on the brain in...
Widely prescribed for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (e.g., methylphenidate) have been studied for their chronic effects on the brain in prospective designs controlling dosage and adherence. While controlled approaches are essential, they do not approximate real-world stimulant exposure contexts where medication interruptions, dosage non-compliance, and polypharmacy are common. Brain changes in real-world conditions are largely unexplored. To fill this gap, we capitalized on the observational design of the Adolescent Brain Cognitive Development (ABCD) study to examine effects of stimulants on large-scale bilateral cortical networks' resting-state functional connectivity (rs-FC) with 6 striatal regions (left and right caudate, putamen, and nucleus accumbens) across two years in children with ADHD. Bayesian hierarchical regressions revealed associations between stimulant exposure and change in rs-FC of multiple striatal-cortical networks, affiliated with executive and visuo-motor control, which were not driven by general psychotropic medication. Of these connections, three were selective to stimulants versus stimulant naive: reduced rs-FC between caudate and frontoparietal network, and between putamen and frontoparietal and visual networks. Comparison with typically developing children in the ABCD sample revealed stronger rs-FC reduction in stimulant-exposed children for putamen and frontoparietal and visual networks, suggesting a normalizing effect of stimulants. 14% of stimulant-exposed children demonstrated reliable reduction in ADHD symptoms, and were distinguished by stronger rs-FC reduction between right putamen and visual network. Thus, stimulant exposure for a two-year period under real-world conditions modulated striatal-cortical functional networks broadly, had a normalizing effect on a subset of networks, and was associated with potential therapeutic effects involving visual attentional control.
PubMed: 38562872
DOI: 10.1101/2024.03.18.24304470 -
Current Research in Toxicology 2024Full treatment of the second most common neurodegenerative disorder, Parkinson's disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine...
Full treatment of the second most common neurodegenerative disorder, Parkinson's disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine (AMPH) and methylphenidate (MPH), were shown to be neuroprotective against stroke and other neuronal injury diseases, this study aimed to evaluate their neuroprotective potential against two dopaminergic neurotoxicants, 6-hydroxydopamine (6-OHDA) and paraquat (PQ), in differentiated human dopaminergic SH-SY5Y cells. Neither cytotoxicity nor mitochondrial membrane potential changes were seen following a 24-hour exposure to either therapeutic concentration of AMPH or MPH (0.001-10 μM). On the other hand, a 24-hour exposure to 6-OHDA (31.25-500 μM) or PQ (100-5000 μM) induced concentration-dependent mitochondrial dysfunction, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and lysosomal damage, evaluated by the neutral red uptake assay. The lethal concentrations 25 and 50 retrieved from the concentration-toxicity curves in the MTT assay were 99.9 µM and 133.6 µM for 6-OHDA, or 422 µM and 585.8 µM for PQ. Both toxicants caused mitochondrial membrane potential depolarization, but only 6-OHDA increased reactive oxygen species (ROS). Most importantly, PQ-induced toxicity was partially prevented by 1 μM of AMPH or MPH. Nonetheless, neither AMPH nor MPH could prevent 6-OHDA toxicity in this experimental model. According to these findings, AMPH and MPH may provide some neuroprotection against PQ-induced neurotoxicity, but further investigation is required to determine the exact mechanism underlying this protection.
PubMed: 38562456
DOI: 10.1016/j.crtox.2024.100165 -
Epilepsy & Behavior Reports 2024A case study of a child with childhood absence epilepsy and hyperactivity introduces the discussion around the psychiatric diagnosis, differential considerations, and...
A case study of a child with childhood absence epilepsy and hyperactivity introduces the discussion around the psychiatric diagnosis, differential considerations, and pharmacologic treatment options for ADHD/hyperactivity in children with epilepsy. Most of the time, ADHD in children with epilepsy is an inattentive form. The assessment emphasizes the need to differentiate ADHD symptoms from other psychiatric comorbidities. This is also crucial to evaluate when symptoms emerged, their impact on daily life, and if it could be a potential medication side effect. Speaking about hyperactivity signs, differential diagnoses include anxiety disorders, autism spectrum disorders, learning disabilities, and thyroid disorders. Valproate use is associated with an exacerbation of attentional issues in childhood absence epilepsy, but there are also studies suggesting its possible role in hyperactivity symptoms. Regarding pharmacologic treatment, limited studies exist on ADHD management in children with epilepsy. Methylphenidate shows effectiveness without significant risk of epilepsy worsening. Atomoxetine and clonidine, usually use in ADHD, lack sufficient data for efficacy and safety in children with epilepsy and ADHD. Pharmacologic treatment should be a part of a global management plan that involves psychoeducation, environmental adaptations, and collaborative efforts between healthcare providers, caregivers, and schools.
PubMed: 38532901
DOI: 10.1016/j.ebr.2024.100660 -
Physiology & Behavior May 2024The utilization of methylphenidate (MPH) is experiencing a notable surge within the adult population. This growth can be attributed to two key factors: its recreational...
BACKGROUND
The utilization of methylphenidate (MPH) is experiencing a notable surge within the adult population. This growth can be attributed to two key factors: its recreational and cognitive enhancement purposes, as well as the rising prevalence of ADHD diagnoses within this population. This study examined acute and chronic oral MPH effects on attention in male and female Wistar rats. To this end, we used a prepulse inhibition (PPI) task, which is widely used to assess psychoactive drug effects in both humans and rodents. This task allowed us to evaluate changes in attention by analyzing sensorimotor gating associated with stimulus selection process.
METHODS
Animals were administered a clinically relevant dose of MPH (5 mg/kg) daily for seven days. The estrous cycle phases of the female rats were measured during behavioral sessions. The PPI task was conducted 20 min after drug administration on day 1 (acute), day 7 (chronic), and 48 h post-treatment.
RESULTS
Results indicated that both acute and chronic MPH treatment impaired PPI expression in male rats, but not in female rats, regardless of their estrous cycle phase. Furthermore, a differential effect of chronic MPH treatment on the PPI task was found in male rats. Specifically, on the seventh treatment day, the PPI effect was observed when animals undertook the PPI task for the first time but was impaired in those animals in which the initial PPI session occurred under the acute influence of the drug (day 1).
CONCLUSIONS
These findings suggest that the impact of MPH on sensorimotor gating responses may vary based on sex and task experience, possibly leading to state-dependent effects in healthy individuals.
Topics: Humans; Female; Male; Rats; Animals; Methylphenidate; Rats, Wistar; Central Nervous System Stimulants; Prepulse Inhibition; Sex Characteristics
PubMed: 38531426
DOI: 10.1016/j.physbeh.2024.114526 -
Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.JAMA Network Open Mar 2024Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD...
IMPORTANCE
Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients.
OBJECTIVE
To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023.
EXPOSURE
Use of specific ADHD medications.
MAIN OUTCOMES AND MEASURES
The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models.
RESULTS
A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92).
CONCLUSIONS AND RELEVANCE
In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.
Topics: Adolescent; Young Adult; Humans; Male; Adult; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Cohort Studies; Lisdexamfetamine Dimesylate; Methylphenidate; Amphetamine
PubMed: 38506810
DOI: 10.1001/jamanetworkopen.2024.2859 -
GMS Journal For Medical Education 2024Students face great challenges at the beginning of and during their studies. Competitive experience, exam anxiety, and especially the new performance requirements often...
BACKGROUND
Students face great challenges at the beginning of and during their studies. Competitive experience, exam anxiety, and especially the new performance requirements often cause test anxiety and stressful experiences. The extent of substance use in terms of neuroenhancement (NE) is unclear. Evidence shows associations between NE, increased stress levels, and mental health.
OBJECTIVES
We aim to determine the prevalence of NE and alcohol and tobacco use among college students. We also investigate the associations between NE and ADHD, anxiety, depression, and stress experience.
METHODS
In spring 2021, an anonymous online cross-sectional survey was conducted among students of medicine, dentistry, business economics, and business informatics in Würzburg. The survey included the instruments ASRS (ADHD), PSS-10 (stress), PHQ-4 (depression and anxiety), and AUDIT-C (alcohol comsumption), as well as questions about consumption patterns, prior knowledge, and reasons for NE.
RESULTS
Of the 5564 students who were invited to participate, 1010 completed the questionnaire (18.2%). Of these, 12.4% indicated NE for the studied period. NE was used in particular during preparations for exams, to enhance performance, and/or to regulate emotions, most commonly through caffeine tablets, cannabis, and methylphenidate. NE was associated with risky use of alcohol or tobacco, and to a lesser extent with ADHD symptoms and stress experience.Conclusions: Students are at risk of substance abuse and NE. Effective stress management and prevention approaches as well as low-threshold services are needed to identify and support students with risk profiles.
Topics: Humans; Cross-Sectional Studies; Mental Health; Students; Substance-Related Disorders; Surveys and Questionnaires
PubMed: 38504866
DOI: 10.3205/zma001664 -
Innovations in Clinical Neuroscience 2024In our case report, a 29-year-old male patient with a known history of schizophrenia presented with altered mental status and catatonia and was found to have an enlarged...
In our case report, a 29-year-old male patient with a known history of schizophrenia presented with altered mental status and catatonia and was found to have an enlarged (21mm) cavum septum pellucidum (CSP) on magnetic resonance imaging (MRI). He was subsequently treated with escitalopram, olanzapine, methylphenidate, lorazepam, and eight electroconvulsive therapy (ECT) treatments during his hospital course, after which his catatonia improved. We compared this to other cases in which a large CSP was identified and discussed the possibility of increased susceptibility to psychosis, specifically catatonia, which might be associated with this developmental anomaly.
PubMed: 38495604
DOI: No ID Found -
CNS Drugs Apr 2024An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use...
BACKGROUND
An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described.
OBJECTIVE
This study aimed to describe ADHD medication use patterns from 1 year before pregnancy to 1 year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories.
METHODS
The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups.
RESULTS
Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%).
CONCLUSION
We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.
Topics: Pregnancy; Humans; Female; Adult; Attention Deficit Disorder with Hyperactivity; Cohort Studies; Methylphenidate; Registries; Central Nervous System Stimulants
PubMed: 38489019
DOI: 10.1007/s40263-024-01076-1