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JAMA Jul 2024
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Child; Adolescent
PubMed: 38842814
DOI: 10.1001/jama.2024.8925 -
JAMA Jul 2024
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Child; Adolescent
PubMed: 38842802
DOI: 10.1001/jama.2024.8922 -
Pharmacoepidemiology and Drug Safety Jun 2024Methylphenidate (MPH) is a common treatment of attention-deficit/hyperactivity disorder (ADHD). Concern has been raised regarding its cardiovascular safety, partly in...
INTRODUCTION
Methylphenidate (MPH) is a common treatment of attention-deficit/hyperactivity disorder (ADHD). Concern has been raised regarding its cardiovascular safety, partly in relation with its micromolar affinity for the 5-HT receptor, whose activation may result in valvular heart disease (VHD).
METHODS
To explore the association between the use of MPH and VHD reporting, we performed a disproportionality analysis within the WHO global safety database (VigiBase) using data, since inception until March 6th 2024, from: (i) the full database and (ii) different age groups (children/adolescents 6-17 years; adults 18-64 years). To avoid competition bias, safety reports with amphetamine-like appetite suppressants were excluded. Disproportionality was expressed using reporting odds-ratio (ROR) and its 95% confidence interval (CI).
RESULTS
Of 29 129 spontaneous reports with MPH, 23 VHD cases (7.9 per 10 000 reports) were identified, including 13 adults and 10 children. Most cases concerned injury on the mitral valve. A disproportionate reporting was observed overall (ROR 1.6, 95% CI 1.1-2.4). Analysis according to age group found that disproportionality in VHD reporting was found in adults only (ROR 2.7, 95% CI 1.6-4.7) but not in children/adolescents (ROR 1.7, 95% CI 0.9-3.2). Furthermore, amongst MPH users only, VHD reporting was higher in adults compared to children (ROR 2.7, 95% CI 1.2-6.3).
CONCLUSION
VHD reporting appears rare with MPH compared to other adverse events and is increased in adults only. Our findings support a potential safety signal of VHD in adults exposed to MPH. A risk in that population cannot be excluded and requires further assessment.
Topics: Humans; Adolescent; Child; Pharmacovigilance; Heart Valve Diseases; Adult; Young Adult; Methylphenidate; Male; Central Nervous System Stimulants; Middle Aged; Female; Attention Deficit Disorder with Hyperactivity; Adverse Drug Reaction Reporting Systems; Databases, Factual; Age Factors
PubMed: 38837561
DOI: 10.1002/pds.5814 -
Frontiers in Behavioral Neuroscience 2024[This corrects the article DOI: 10.3389/fnbeh.2023.1251144.].
[This corrects the article DOI: 10.3389/fnbeh.2023.1251144.].
PubMed: 38835839
DOI: 10.3389/fnbeh.2024.1431914 -
Journal of the American Academy of... May 2024We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to...
OBJECTIVE
We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to understand whether this effect differs between stimulants and non-stimulants.
METHOD
From the dataset of a published network meta-analysis (Cortese et al., 2018), updated on 27 February 2023 (https://med-adhd.org/), we identified randomized controlled trials (RCTs) of ADHD medications for individuals aged 6 years or more with a diagnosis of ADHD based on the DSM (from third to fifth editions) or the International Classification of Diseases (ICD; ninth or tenth revision), reporting data on QoL (measured with a validated scale). The risk of bias for each RCTs was assessed using the Cochrane Risk of Bias tool 2. Multi-level meta-analytic models were conducted with R 4.3.1.
RESULTS
We included 17 RCTs (5,388 participants in total; 56% randomized to active medication) in the meta-analyses. We found that amphetamines (Hedges g = 0.51, 95% CI = 0.08, 0.94), methylphenidate (0.38; 0.23, 0.54), and atomoxetine (0.30; 0.19, 0.40) were significantly more efficacious than placebo in improving QoL in people with ADHD, with moderate effect size. For atomoxetine, these effects were not moderated by the length of intervention, and did not differ between children/adolescents and adults.
CONCLUSION
In addition to being efficacious in reducing ADHD core symptom severity, both stimulant and non-stimulant medications are efficacious in improving QoL in people with ADHD, albeit with lower effect sizes. Future research should explore whether, and to what degree, combining pharmacological and non-pharmacological interventions is likely to further improve QoL in people with ADHD.
STUDY PREREGISTRATION INFORMATION
Effects of pharmacological treatment for ADHD on quality of life: a systematic review and meta-analysis; https://osf.io/;qvgps.
PubMed: 38823477
DOI: 10.1016/j.jaac.2024.05.023 -
Expert Opinion on Emerging Drugs Jun 2024Agitation, psychosis, and apathy are prevalent and highly distressing neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD) that have been linked to numerous... (Review)
Review
INTRODUCTION
Agitation, psychosis, and apathy are prevalent and highly distressing neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD) that have been linked to numerous negative outcomes, including increased mortality, worsened cognitive decline, and caregiver burden. Current treatments for AD-associated agitation, namely atypical antipsychotics, provide some benefits but may increase the risk of serious adverse events and death. Meanwhile, no pharmacotherapies have been approved by regulatory agencies for the treatment of psychosis or apathy in AD. Over the past decade, many new and repurposed drugs have emerged as potential therapeutic options for managing these challenging NPS.
AREAS COVERED
This review aims to provide a comprehensive summary of pharmacotherapies that have recently been investigated in phase 2 and 3 clinical trials for the treatment of agitation, psychosis, or apathy in AD.
EXPERT OPINION
Novel atypical antipsychotics, serotonergic antidepressants, cannabinoids, and dextromethorphan combination drugs have shown promising results for alleviating agitation. Pimavanserin appears to be the most effective emerging therapy for psychosis, while methylphenidate has demonstrated good efficacy for apathy. Further research on biomarkers of NPS severity and treatment response, as well as continued improvements in methodological approaches are needed to advance the field.
PubMed: 38822731
DOI: 10.1080/14728214.2024.2363215 -
Growth Hormone & IGF Research :... Jun 2024To assess the growth hormone (GH) and Dopamine (DA) response to exercise in children with attention-deficit hyperactivity disorder (ADHD) with and without...
PURPOSE
To assess the growth hormone (GH) and Dopamine (DA) response to exercise in children with attention-deficit hyperactivity disorder (ADHD) with and without methylphenidate (MP). We hypothesized that the GH and DA response to the exercise with MP would be siginicantly lower.
METHODS
Twenty children participated in the study (12 males and 8 females, age range 9-13 years). Ten with ADHD and 10 controls. Participants with ADHD performed an exercise test twice, with and without MP while controls performed one exercise test. Blood samples for GH and DA were collected before, at peak, 30 and 60 min after the end of exercise.
RESULTS
Compared to controls, children with ADHD with and without MP, had a significantly lower GH (P < .002) and DA (P < .01) responses to exercise. In participants with ADHD, a significantly greater GH response (p < .04) to exercise was found when MP administered to the children before exercise, yet this response was still significantly lower than controls.
CONCLUSIONS
GH and DA excretion after an exercise challenge in children with ADHD is impaired. MP slightly attenuates the GH blunted response. This may link ADHD with growth impairment in some children and explain previous findings indicating that the final adult height is usually not compromised in children with ADHD treated with MP. The combined exercise and stimulant treatment therapeutic effects needs to be further explored.
TRIAL REGISTRATION NUMBER
NCT00945971.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Child; Methylphenidate; Female; Male; Adolescent; Exercise; Dopamine; Central Nervous System Stimulants; Human Growth Hormone; Case-Control Studies; Exercise Test
PubMed: 38820857
DOI: 10.1016/j.ghir.2024.101596 -
Brain Research Sep 2024Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus...
Traumatic brain injury (TBI) is a complex pathophysiological process that results in a variety of neurotransmitter, behavioral, and cognitive deficits. The locus coeruleus-norepinephrine (LC-NE) system is a critical regulator of arousal levels and higher executive processes affected by TBI including attention, working memory, and decision making. LC-NE axon injury and impaired signaling within the prefrontal cortex (PFC) is a potential contributor to the neuropsychiatric symptoms after single, moderate to severe TBI. The majority of TBIs are mild, yet long-term cognitive deficits and increased susceptibility for further injury can accumulate after each repetitive mild TBI. As a potential treatment for restoring cognitive function and daytime sleepiness after injury psychostimulants, including methylphenidate (MPH) that increase levels of NE within the PFC, are being prescribed "off-label". The impact of mild and repetitive mild TBI on the LC-NE system remains limited. Therefore, we determined the extent of LC-NE and arousal dysfunction and response to therapeutic doses of MPH in rats following experimentally induced single and repetitive mild TBI. Microdialysis measures of basal NE efflux from the medial PFC and arousal measures were significantly lower after repetitive mild TBI. Females showed higher baseline PFC-NE efflux than males following single and repetitive mild TBI. In response to MPH challenge, males exhibited a blunted PFC-NE response and persistent arousal levels following repetitive mild TBI. These results provide critical insight into the role of catecholamine system dysfunction associated with cognitive deficits following repeated injury, outcome differences between sex/gender, and lack of success of MPH as an adjunctive therapy to improve cognitive function following injury.
Topics: Animals; Male; Norepinephrine; Female; Rats, Sprague-Dawley; Prefrontal Cortex; Central Nervous System Stimulants; Methylphenidate; Brain Concussion; Rats; Brain Injuries, Traumatic; Locus Coeruleus; Arousal; Microdialysis
PubMed: 38815643
DOI: 10.1016/j.brainres.2024.149040 -
Frontiers in Psychiatry 2024Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs...
INTRODUCTION
Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons.
METHODS
Here, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay.
RESULTS
Methylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity.
DISCUSSION
Our results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity.
PubMed: 38779546
DOI: 10.3389/fpsyt.2024.1385502 -
Acta Obstetricia Et Gynecologica... Jul 2024There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine...
INTRODUCTION
There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine among the general population of Danish pregnant women.
MATERIAL AND METHODS
In this anonymous, national, cross-sectional, descriptive study, pregnant women were invited when attending an ultrasound scan between November 2019 and December 2020 at nine Danish hospitals. Women submitted a urine sample and filled out a questionnaire. Urine samples were screened on-site with a qualitative urine dipstick for 15 substances including alcohol, nicotine, opioids, amphetamines, cannabis, and benzodiazepines. All screen-positive urine samples underwent secondary quantitative analyses with gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results were compared to questionnaire information to analyze the validity of self-reporting and to examine possible cross-reactions.
RESULTS
A total of 1903 of 2154 invited pregnant women participated (88.3%). The prevalence of dipstick-positive urine samples was 25.0%. 44.0% of these were confirmed positive, resulting in a total confirmed prevalence of 10.8%. The prevalence of nicotine use was 10.1%-and for all other substances, <0.5%. Nicotine use was more prevalent among younger pregnant women, while other substance use appeared evenly distributed over age groups. Self-reporting of use of nicotine products was high (71.1%), but low for cannabis and alcohol intake (0% and 33.3%, respectively). Prescription medication explained almost all cases of oxycodone, methylphenidate, and benzodiazepine use.
CONCLUSIONS
Substance use among pregnant women consisted mainly of nicotine. Dipstick screening involved risks of false negatives and false positives. Except for alcohol intake and cannabis use, dipstick analyses did not seem to provide further information than self-reporting. LC-MS/MS analyses remain gold standard, and future role of dipstick screenings should be discussed.
Topics: Humans; Female; Pregnancy; Cross-Sectional Studies; Denmark; Adult; Substance-Related Disorders; Substance Abuse Detection; Prevalence; Pregnancy Complications; Surveys and Questionnaires; Young Adult; Tandem Mass Spectrometry; Chromatography, Liquid
PubMed: 38778571
DOI: 10.1111/aogs.14862