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Epilepsia Open Apr 2024Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD,... (Randomized Controlled Trial)
Randomized Controlled Trial
Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial.
BACKGROUND
Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD.
METHODS
A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment.
RESULTS
The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3.
CONCLUSION
Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy.
PLAIN LANGUAGE SUMMARY
Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Phosphatidylserines; Treatment Outcome; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Epilepsy; Dietary Supplements
PubMed: 38173190
DOI: 10.1002/epi4.12892 -
Physiological Research Dec 2023Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine...
Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine and together suppress acute and chronic pain. In clinical practice, methylphenidate has been used as a treatment for ADHD and changes of pain threshold have been noted in these patients. The aim of this study was to determine the effect of methylphenidate in an animal model of peripheral neuropathic pain. Neuropathic pain was modeled by the chronic constriction of the sciatic nerve (CCI) in Wistar rats. We evaluated the effect of methylphenidate (1 mg/kg, s.c.) on evoked pain (reflex tests - plantar test, vonFrey test and operant test - thermal place preference) and on spontaneous pain (conditioned place preference). CCI induced thermal, mechanical and cold hyperalgesia/allodynia. Methyphenidate suppressed mechanical and cold hyperalgesia/allodynia, while had no effect on thermal one. Therefore, methylphenidate seems to be a new potential pharmacotherapy for the treatment of neuropathic pain.
Topics: Humans; Rats; Animals; Hyperalgesia; Methylphenidate; Rats, Wistar; Disease Models, Animal; Neuralgia
PubMed: 38165759
DOI: 10.33549/physiolres.935215 -
The South African Journal of Psychiatry... 2023Attention-deficit/hyperactivity disorder (ADHD) is a neuro-developmental disorder prevalent among children and adults. Adults living with ADHD can experience significant... (Review)
Review
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a neuro-developmental disorder prevalent among children and adults. Adults living with ADHD can experience significant distress affecting their daily functioning on emotional, physical, interpersonal, familial and financial levels. Intervention programmes may be a way to mitigate these challenges.
AIM
This review identified good evidence-based intervention studies for adults with ADHD and described the usefulness of these interventions.
METHOD
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles were searched from 2009 to 2019 across four medical- and psychological-focused electronic databases using EBSCOhost. All articles selected for the review's thematic meta-synthesis were appraised by attaining a threshold score of at least 61%, using the Smith-Franciscus-Swartbooi appraisal tool. Two autonomous reviewers engaged in the review process. The study adhered to all ethical principles pertaining to systematic review practice.
RESULTS
Forty studies were identified for summation, including pharmacological, non-pharmacological and neuro-stimulation approaches. Most interventions used a multimodal approach. Results indicated the most effective stimulant and non-stimulant as methylphenidate and atomoxetine, respectively. Effective non-pharmacological approaches to treatment were identified as cognitive-behavioural treatment, mindfulness-based approaches, psycho-education and dialectical-focused therapies. Bright light treatment and neurofeedback were reported as the most efficacious neuro-stimulatory methods.
CONCLUSION
Pharmacological and non-pharmacological approaches, as well as neuro-stimulation or a blend of these approaches were acknowledged as the most effective recent modalities in the treatment of adult ADHD.
CONTRIBUTION
This review reported on the most current approaches to treat adult ADHD. This will facilitate a better understanding and informed decisions with regard to dealing with adult ADHD.
PubMed: 38126038
DOI: 10.4102/sajpsychiatry.v29i0.2152 -
Proceedings of the National Academy of... Dec 2023The amplitude of low-frequency fluctuations (ALFF) and global functional connectivity density (gFCD) are fMRI (Functional MRI) metrics widely used to assess resting...
The amplitude of low-frequency fluctuations (ALFF) and global functional connectivity density (gFCD) are fMRI (Functional MRI) metrics widely used to assess resting brain function. However, their differential sensitivity to stimulant-induced dopamine (DA) increases, including the rate of DA rise and the relationship between them, have not been investigated. Here we used, simultaneous PET-fMRI to examine the association between dynamic changes in striatal DA and brain activity as assessed by ALFF and gFCD, following placebo, intravenous (IV), or oral methylphenidate (MP) administration, using a within-subject double-blind placebo-controlled design. In putamen, MP significantly reduced D receptor availability and strongly reduced ALFF and increased gFCD in the brain for IV-MP (Cohen's d > 1.6) but less so for oral-MP (Cohen's d < 0.6). Enhanced gFCD was associated with both the level and the rate of striatal DA increases, whereas decreased ALFF was only associated with the level of DA increases. These findings suggest distinct representations of neurovascular activation with ALFF and gFCD by stimulant-induced DA increases with differential sensitivity to the rate and the level of DA increases. We also observed an inverse association between gFCD and ALFF that was markedly enhanced during IV-MP, which could reflect an increased contribution from MP's vasoactive properties.
Topics: Brain; Dopamine; Magnetic Resonance Imaging; Methylphenidate; Double-Blind Method
PubMed: 38109535
DOI: 10.1073/pnas.2314596120 -
Alpha Psychiatry Sep 2023Long-acting methylphenidate (MPH), a psychostimulant agent, is widely used in the treatment of attention-deficit hyperactivity disorder (ADHD). Methylphenidate might...
BACKGROUND
Long-acting methylphenidate (MPH), a psychostimulant agent, is widely used in the treatment of attention-deficit hyperactivity disorder (ADHD). Methylphenidate might cause an increment in the risk of lethal arrhythmias by deteriorating ventricular repolarization. QT intervals, the corrected QT (QTc), QT dispersion, T-peak to T-end (TpTe), and the TpTe/QTc ratio are the most utilized indicators of ventricular repolarization in electrocardiogram (ECG). The present study was conducted to examine the effects of long-term MPH use on the ECG in pediatric patients.
METHODS
A total of 52 children with ADHD and 51 age- and gender-matched controls were enrolled in the study. The children had been using MPH regularly for at least 6 months. Comparisons were made regarding ECG parameters, including the mean intervals of QT, QTc, QTc dispersion interval duration, TpTe intervals, TpTe/QT, and TpTe/QTc ratio.
RESULTS
The median duration of treatment with MPH was 30 months (minimum-maximum: 6-120), and the median MPH dose was 30 mg/day (minimum-maximum: 18-54). The main findings showed significantly prolonged P-wave dispersion, TpTe interval, TpTe dispersion, and TpTe/QT and TpTe/QTc ratios in the ADHD group compared to the healthy controls ( < .001). These parameters were not associated with MPH dose or treatment duration. Additionally, nearly half of the patients had QTc values of 460 ms or higher, but there were no significant differences in treatment duration and dose compared to the remaining group ( = .792 and = .126).
CONCLUSION
Methylphenidate may have proarrhythmogenic effects in children with ADHD, which may not be adversely affected by long-term use and treatment dose. Considering the extensive use of MPH, cardiac monitoring of these children is important.
PubMed: 38105780
DOI: 10.5152/alphapsychiatry.2023.231185 -
BMJ Open Dec 2023Attention deficit hyperactivity disorder (ADHD) affects 5%-10% of paediatric population and is reportedly more common in children with type 1 diabetes (T1D),...
Lisdexamphetamine versus methylphenidate for paediatric patients with attention-deficit hyperactivity disorder and type 1 diabetes (LAMAinDiab): protocol for a multicentre, randomised cross-over clinical trial in an outpatient telemedicine-supported setting.
INTRODUCTION
Attention deficit hyperactivity disorder (ADHD) affects 5%-10% of paediatric population and is reportedly more common in children with type 1 diabetes (T1D), exacerbating its clinical course. Proper treatment of ADHD in such patients may thus provide neurological and metabolic benefits. To test this, we designed a non-commercial second phase clinical trial comparing the impact of different pharmacological interventions for ADHD in children with T1D.
METHODS AND ANALYSIS
This is a multicentre, randomised, open-label, cross-over clinical trial in children and adolescents with ADHD and T1D. The trial will be conducted in four reference paediatric diabetes centres in Poland. Over 36 months, eligible patients with both T1D and ADHD (aged 8-16.5 years, T1D duration >1 year) will be offered participation. Patients' guardians will undergo online once-weekly training sessions behaviour management for 10 weeks. Afterward, children will be randomised to methylphenidate (long-release capsule, doses 18-36-54 mg) versus lisdexamphetamine (LDX, 30-50-70 mg). Pharmacotherapy will continue for 6 months before switching to alternative medication. Throughout the trial, the participants will be evaluated every 3 months by their diabetologist and online psychological assessments. The primary endpoint (ADHD symptom severity, Conners 3.0 questionnaire) will be assessed by a blinded investigator. Secondary endpoints will include HbA1c, continuous glucose monitoring indices and quality-of-life (PedsQL).
ETHICS AND DISSEMINATION
The trial is approved by Bioethical Committee at Medical University of Lodz and Polish regulatory agency (RNN/142/22/KE, UR/DBL/D/263/2022). The results will be communicated to the research and clinical community, and Polish agencies responsible for healthcare policy. Patient organisations focused on paediatric T1D will be notified by a consortium member. We hope to use the trial's results to promote collaboration between mental health professionals and diabetes teams, evaluate the economic feasibility of using LDX in patients with both diseases and the long run improve ADHD treatment in children with T1D.
TRIAL REGISTRATION NUMBERS
EU Clinical Trials Register (EU-CTR, 2022-001906-24) and NCT05957055.
Topics: Adolescent; Humans; Child; Attention Deficit Disorder with Hyperactivity; Methylphenidate; Lisdexamfetamine Dimesylate; Diabetes Mellitus, Type 1; Outpatients; Blood Glucose Self-Monitoring; Blood Glucose; Central Nervous System Stimulants; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38086595
DOI: 10.1136/bmjopen-2023-078112 -
Journal of Attention Disorders Mar 2024The aim of this study was to identify patterns of ADHD care, including factors that guide selection and sequencing of treatments in a large nationwide sample of...
OBJECTIVE
The aim of this study was to identify patterns of ADHD care, including factors that guide selection and sequencing of treatments in a large nationwide sample of preschool-aged youth over the past 6 years.
METHOD
A retrospective cohort study utilizing a large electronic health record (TriNetX) of nearly 24,000 children ages 3 to 6 diagnosed with ADHD.
RESULTS
One in three preschoolers with ADHD were prescribed psychotropic medication, most commonly methylphenidate and guanfacine. One in 10 had at least one psychotherapy billing code during the entire assessment with most youth starting medication before psychotherapy. Rates of most treatments, including polypharmacy, increased with comorbid psychiatric disorders or sleep problems and over the course of the coronavirus pandemic.
CONCLUSION
Rates of treatment have increased over time but are still largely inconsistent with published care guidelines that advise therapy before medication. Clinicians appear to prioritize psychiatric comorbidity and sleep problems when selecting treatments.
Topics: Adolescent; Humans; Child, Preschool; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Retrospective Studies; Methylphenidate; Sleep Wake Disorders
PubMed: 38084067
DOI: 10.1177/10870547231215287 -
International Journal of Molecular... Nov 2023Methylphenidate (MPD), known as Ritalin, is a psychostimulant used to treat children, adults, and the elderly. MPD exerts its effects through increasing concentrations...
Dopamine, Norepinephrine and Serotonin Participate Differently in Methylphenidate Action in Concomitant Behavioral and Ventral Tegmental Area, Locus Coeruleus and Dorsal Raphe Neuronal Study in Young Rats.
Methylphenidate (MPD), known as Ritalin, is a psychostimulant used to treat children, adults, and the elderly. MPD exerts its effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the synaptic cleft. Concomitant behavioral and neuronal recording from the ventral tegmental area (VTA), locus coeruleus (LC), and from the dorsal raphe (DR) nucleus, which are the sources of DA, NE, and 5-HT to the mesocorticolimbic circuit, were investigated following acute and repetitive (chronic) saline, 0.6, 2.5, or 10.0 mg/kg MPD. Animals received daily saline or MPD administration on experimental days 1 to 6 (ED1-6), followed by a 3-day washout period and MPD rechallenge on ED10. Each chronic MPD dose elicits behavioral sensitization in some animals while inducing behavioral tolerance in others. The uniqueness of this study is in the evaluation of neuronal activity based on the behavioral response to chronic MPD. Neuronal excitation was observed mainly in brain areas of animals exhibiting behavioral sensitization, while neuronal attenuation following chronic MPD was observed in animals expressing behavioral tolerance. Different ratios of excitatory/inhibitory neuronal responses were obtained from the VTA, LC, or DR following chronic MPD. Thus, each brain area responds differently to each MPD dose used, suggesting that DA, NE, and 5-HT in the VTA, LC, and DR exert different effects.
Topics: Humans; Child; Rats; Animals; Aged; Methylphenidate; Serotonin; Ventral Tegmental Area; Dopamine; Dorsal Raphe Nucleus; Locus Coeruleus; Norepinephrine; Rats, Sprague-Dawley
PubMed: 38068951
DOI: 10.3390/ijms242316628 -
Nutrients Nov 2023Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with...
BACKGROUND
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with potential relevance to Attention Deficit/Hyperactivity Disorder (ADHD). This study investigated this association.
METHODS
The clinical characteristics of 7473 G6PD-deficient patients and 29,892 matched case-controls (selected at a 1:4 ratio) from a cohort of 1,031,354 within the Leumit Health Services database were analyzed using Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables.
RESULTS
In total, 68.7% were male. The mean duration of follow-up was 14.3 ± 6.2 years at a mean age of 29.2 ± 22.3 years. G6PD deficiency was associated with an increased risk of being diagnosed with ADHD (Odds Ratio (OR) = 1.16 [95% CI, 1.08-1.25], < 0.001), seeking care from adult neurologists (OR = 1.30 [95% CI, 1.22-1.38], < 0.001), and consulting adult psychiatrists (OR = 1.12 [95% CI, 1.01-1.24], = 0.048). The use of stimulant medications among G6PD-deficient individuals was 17% higher for the methylphenidate class of drugs (OR = 1.17 [95% CI, 1.08, 1.27], < 0.001), and there was a 16% elevated risk for amphetamine use (OR = 1.16 [95% CI, 1.03, 1.37], = 0.047).
CONCLUSIONS
G6PD deficiency signals an increased risk of ADHD diagnosis, more severe presentations of ADHD and a greater need for psychiatric medications to treat ADHD.
Topics: Adult; Humans; Male; Child; Adolescent; Young Adult; Middle Aged; Female; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Glucosephosphate Dehydrogenase Deficiency; Phosphates; Glucose
PubMed: 38068806
DOI: 10.3390/nu15234948 -
Neuropsychopharmacology Reports Mar 2024Attention-deficit hyperactivity disorder (ADHD) is characterized by persistent symptoms of inattention, hyperactivity, and impulsivity. Both, stimulant and nonstimulant... (Review)
Review
Attention-deficit hyperactivity disorder (ADHD) is characterized by persistent symptoms of inattention, hyperactivity, and impulsivity. Both, stimulant and nonstimulant medications have been approved for the treatment of this disorder. Several Western guidelines recommend the use of prescribed Food and Drug Administration (FDA)-approved medications for ADHD along with parental training in behavior management and behavioral classroom intervention. In 2022, new Japanese guidelines for ADHD were issued, which recommended school environment management and psychosocial treatment as the first-line treatment, with pharmacological treatment added as the second-line treatment. Although Japanese guidelines, including pharmacological treatments, have been established, the guidelines and utilization of ADHD medications across Asian regions are unclear. Therefore, to appropriately evaluate the strategy of pharmacological treatments for ADHD, we investigated Asian regional guidelines for ADHD medication in children. We also reviewed the guidelines in Malaysia, Singapore, India, and the Republic of Korea and found that these guidelines differ from Western guidelines.
Topics: United States; Child; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Asia
PubMed: 38059346
DOI: 10.1002/npr2.12381