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Neuroscience and Biobehavioral Reviews Jul 2024Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant... (Meta-Analysis)
Meta-Analysis Review
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34-0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36-0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Executive Function; Central Nervous System Stimulants; Methylphenidate; Atomoxetine Hydrochloride; Memory, Short-Term
PubMed: 38718988
DOI: 10.1016/j.neubiorev.2024.105703 -
Case Reports in Neurological Medicine 2024Infantile dystonia-parkinsonism type 2 (PKDYS2) is a rare inherited autosomal recessive movement disorder with onset in infancy. The disease is associated with a...
Infantile dystonia-parkinsonism type 2 (PKDYS2) is a rare inherited autosomal recessive movement disorder with onset in infancy. The disease is associated with a mutation in the solute carrier family 18 member A2 gene (). There are reports of trials with dopaminergic drugs and the condition of patients given levodopa almost always worsens and dopamine agonists give varying degrees of benefit to some. Here, we report a PKDYS2 patient with a new variant in the gene who underwent multiple trials of pharmacotherapy. The abnormalities in development and neurological examination of the case were first noted at the age of 2 months, and after a series of treatment attempts (e.g., with antiepileptics) and diagnostic procedures, the diagnosis of PKDYS2 was determined when whole exome sequencing (WES) at age 6, revealed a homozygous pathologic variant NM_003054.4:c.1107dup, p.(Val370Serfs91) in the gene. The patient then received treatment with multiple dopaminergic drugs (e.g., levodopa, pramipexole, and methylphenidate). The patient with PKDYS2 harbored a new variant in The phenotype of the patient resembles that of some previously reported patients with PKDYS2. The patient received minor benefits from certain dopaminergic drugs, such as pramipexole, but side effects led to the discontinuation of tested medications.
PubMed: 38716424
DOI: 10.1155/2024/4767647 -
Eye (London, England) May 2024Attention deficit hyperactivity disorder (ADHD) therapies including atomoxetine, methylphenidate, and amphetamines are some of the most prescribed medications in North...
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) therapies including atomoxetine, methylphenidate, and amphetamines are some of the most prescribed medications in North America. Due to their sympathomimetic action, these drugs are contraindicated in patients with a history of angle closure glaucoma (ACG). This study aims to determine the risk of ACG and open angle glaucoma (OAG) among users of these treatments.
METHODS
This is a retrospective cohort study with a case control analysis using the PharMetrics Plus Database (IQVIA, USA). We created a cohort of new users of atomoxetine, methylphenidate, and amphetamines and they were followed to the first diagnosis of (1) ACG or OAG; or (2) end of follow up. For each case, four age-matched controls were selected. A conditional logistic regression model was used to adjust for confounders and to calculate adjusted incidence-rate-ratios (aIRRs).
RESULTS
A total of 240,257 new users of the ADHD medications were identified. The mean age was 45.0 ± 19.4 years and 55% of the cohort was female. Regular users of atomoxetine and amphetamines had a higher aIRR for developing ACG compared with non-users (aIRR = 2.55 95% CI [1.20-5.43] and 2.27 95% CI [1.42-3.63], respectively); while users of methylphenidate had a higher aIRR for developing OAG (aIRR = 1.23 95% CI [1.05-1.59]).
CONCLUSIONS
Use of amphetamines and atomoxetine had a higher risk for ACG, while use of methylphenidate was associated with a higher risk for OAG. Given the prevalence of ADHD medication use (medically and recreationally), our current data on their associated risk of glaucoma have profound public health implications.
PubMed: 38710937
DOI: 10.1038/s41433-024-03100-6 -
The Journal of Head Trauma...To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation.
OBJECTIVE
To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation.
SETTING
Inpatient pediatric rehabilitation.
PARTICIPANTS
In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission.
DESIGN
Multicenter, retrospective medical record review.
MAIN MEASURES
Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day).
RESULTS
Patients who received MPH were older (P = .011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P = .001) and at discharge (P = .030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported.
CONCLUSION
This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored.
Topics: Humans; Methylphenidate; Child; Female; Brain Injuries, Traumatic; Male; Adolescent; Child, Preschool; Retrospective Studies; Central Nervous System Stimulants; Infant; Practice Patterns, Physicians'; Young Adult; Inpatients; Length of Stay; Rehabilitation Centers
PubMed: 38709832
DOI: 10.1097/HTR.0000000000000889 -
Expert Opinion on Drug Metabolism &... May 2024Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are among the most abundant hydrolases in humans, catalyzing the metabolism of numerous clinically important... (Review)
Review
INTRODUCTION
Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are among the most abundant hydrolases in humans, catalyzing the metabolism of numerous clinically important medications, such as methylphenidate and clopidogrel. The large interindividual variability in the expression and activity of CES1 and CES2 affects the pharmacokinetics (PK) and pharmacodynamics (PD) of substrate drugs.
AREAS COVERED
This review provides an up-to-date overview of CES expression and activity regulations and examines their impact on the PK and PD of CES substrate drugs. The literature search was conducted on PubMed from inception to January 2024.
EXPERT OPINION
Current research revealed modest associations of CES genetic polymorphisms with drug exposure and response. Beyond genomic polymorphisms, transcriptional and posttranslational regulations can also significantly affect CES expression and activity and consequently alter PK and PD. Recent advances in plasma biomarkers of drug-metabolizing enzymes encourage the research of plasma protein and metabolite biomarkers for CES1 and CES2, which could lead to the establishment of precision pharmacotherapy regimens for drugs metabolized by CESs. Moreover, our understanding of tissue-specific expression and substrate selectivity of CES1 and CES2 has shed light on improving the design of CES1- and CES2-activated prodrugs.
Topics: Humans; Carboxylic Ester Hydrolases; Animals; Polymorphism, Genetic; Pharmaceutical Preparations; Prodrugs; Biomarkers; Carboxylesterase
PubMed: 38706437
DOI: 10.1080/17425255.2024.2348491 -
The New Zealand Medical Journal May 2024To report dispensing trends for attention-deficit hyperactivity disorder (ADHD) in Aotearoa New Zealand, focussing on adults in order to highlight increasing demand for...
AIM
To report dispensing trends for attention-deficit hyperactivity disorder (ADHD) in Aotearoa New Zealand, focussing on adults in order to highlight increasing demand for ADHD treatment by adults and to prompt discussion.
METHOD
Demographic and dispensing data for ADHD were obtained from the Pharmaceutical Collection between the years 2006 and 2022. This was stratified according to child (<18 years) and adult (≥18 years) populations. Population dispensing rates for methylphenidate and atomoxetine were calculated. Key findings are reported to reveal demographic and dispensing trends for medication treated ADHD in Aotearoa New Zealand.
RESULTS
More males are dispensed ADHD medication than females, although this is less evident for adults (54.8% male). Māori adults are dispensed ADHD medication at a lower rate (10.1%) than Māori children (22.9%). There was a 10-fold increase in dispensing of ADHD medication for adults compared to a three-fold increase for children over the study period. New dispensing for adults doubled between 2011 and 2022.
CONCLUSION
Medication treatment for adult ADHD is increasing in Aotearoa New Zealand and includes treatment for persisting childhood ADHD and new diagnoses made in adulthood. Despite increases, dispensing rates for ADHD remain lower than prevalence estimates, suggesting a significant treatment gap. Addressing the treatment gap for ADHD may reduce negative effects of ADHD, but wider social influences should also be considered.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Young Adult; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; New Zealand; Maori People
PubMed: 38696829
DOI: 10.26635/6965.6392 -
AJP Reports Apr 2024Type 1 narcolepsy (with cataplexy) is a rare disorder affecting the central nervous system and is characterized by the inability to control sleep-wake cycles. There...
Type 1 narcolepsy (with cataplexy) is a rare disorder affecting the central nervous system and is characterized by the inability to control sleep-wake cycles. There is a paucity of data regarding management during pregnancy. This is a 23-year-old primigravida with narcolepsy and cataplexy, treated with methylphenidate in the third trimester, resulting in an improvement of episodes of cataplexy. A review of the literature reveals information regarding options for medical management and the mode of delivery for these women. Type 1 narcolepsy can be treated with medications after consideration of risks and benefits. For patients who are symptomatic at the time of birth, cesarean section may be the preferred mode of delivery in women with type 1 narcolepsy.
PubMed: 38682093
DOI: 10.1055/a-2297-4583 -
Brain Research Bulletin Jun 2024
Retraction Notice to "Possible involvement of CREB/BDNF signaling pathway in neuroprotective effects of topiramate against methylphenidate induced apoptosis, oxidative stress and inflammation in hippocampus of rats: Molecular, biochemical and histological evidences" [Brain. Res. Bull. 132 (2017)...
PubMed: 38679545
DOI: 10.1016/j.brainresbull.2024.110956 -
NeuroImage Jun 2024Catecholamines and amino acid transmitter systems are known to interact, the exact links and their impact on cognitive control functions have however remained unclear....
Catecholamines and amino acid transmitter systems are known to interact, the exact links and their impact on cognitive control functions have however remained unclear. Using a multi-modal imaging approach combining EEG and proton-magnetic resonance spectroscopy (H-MRS), we investigated the effect of different degrees of pharmacological catecholaminergic enhancement onto theta band activity (TBA) as a measure of interference control during response inhibition and execution. It was central to our study to evaluate the predictive impact of in-vivo baseline GABA+ concentrations in the striatum, the anterior cingulate cortex (ACC) and the supplemental motor area (SMA) of healthy adults under varying degrees of methylphenidate (MPH) stimulation. We provide evidence for a predictive interrelation of baseline GABA+ concentrations in cognitive control relevant brain areas onto task-induced TBA during response control stimulated with MPH. Baseline GABA+ concentrations in the ACC, the striatum, and the SMA had a differential impact on predicting interference control-related TBA in response execution trials. GABA+ concentrations in the ACC appeared to be specifically important for TBA modulations when the cognitive effort needed for interference control was high - that is when no prior task experience exists, or in the absence of catecholaminergic enhancement with MPH. The study highlights the predictive role of baseline GABA+ concentrations in key brain areas influencing cognitive control and responsiveness to catecholaminergic enhancement, particularly in high-effort scenarios.
Topics: Humans; gamma-Aminobutyric Acid; Male; Adult; Female; Young Adult; Proton Magnetic Resonance Spectroscopy; Catecholamines; Methylphenidate; Electroencephalography; Cognition; Brain; Gyrus Cinguli; Theta Rhythm; Executive Function; Central Nervous System Stimulants
PubMed: 38679186
DOI: 10.1016/j.neuroimage.2024.120619 -
Brain Sciences Mar 2024Craving is one of the most important symptoms of cocaine use disorder (CUD) since it contributes to the relapse and persistence of such disorder. This systematic review... (Review)
Review
Craving is one of the most important symptoms of cocaine use disorder (CUD) since it contributes to the relapse and persistence of such disorder. This systematic review aimed to investigate which brain regions are modulated during cocaine craving. The articles were obtained through searches in the Google Scholar, Regional BVS Portal, PubMed, and Scielo databases. Overall, there was a selection of 36 studies with 1574 individuals, the majority being participants with CUD, whereby about 61.56% were individuals with CUD and 38.44% were controls (mean age = 40.4 years). Besides the methodological points, the neurobiological investigations comprised fMRI (58.34%) and PET (38.89%). The induction of cocaine craving was studied using different methods: exposure to cocaine cues (69.45%), stressful stimuli, food cues, and methylphenidate. Brain activations demonstrated widespread activity across the frontal, parietal, temporal, and occipital lobes, basal ganglia, diencephalon, brainstem, and the limbic system. In addition to abnormalities in prefrontal cortex activity, abnormalities in various other brain regions' activity contribute to the elucidation of the neurobiology of cocaine craving. Abnormalities in brain activity are justified not only by the dysfunction of dopaminergic pathways but also of the glutamatergic and noradrenergic pathways, and distinct ways of inducing craving demonstrated the involvement of distinct brain circuits and regions.
PubMed: 38671981
DOI: 10.3390/brainsci14040329