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Duric NS, Assmus J, Børresen H, Golos AD, Socanski D, Duric A, Surmeli T. Quantitative electroencephalography in children with attention deficit hyperactivity disorder and healthy children: Behavioral and age correlates. APPLIED NEUROPSYCHOLOGY. CHILD 2025; 14:194-202. [PMID: 38086349 DOI: 10.1080/21622965.2023.2288865] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/21/2025]
Abstract
This pilot study aimed to identify quantitative electroencephalographic (qEEG) biomarkers for children and adolescents with attention deficit hyperactivity disorder (ADHD). We examined whether qEEG power correlates with the behavioral symptoms. We included 89 children with ADHD and 77 healthy children as a control group. We conducted EEG spectral analysis in the eyes-closed and eyes-opened conditions and compared the findings with a normative database (Human Brain Index). We measured behavioral parameters by using scales proposed by Barkley. The findings revealed an age-dependent decrease in qEEG power in children with ADHD. We found significant discrimination between children with ADHD and healthy children in the theta/beta ratio and theta activity in the frontal area. We found a notable increasing trend in beta activity across two age groups (6-10 years and > 10 years). Correlation analysis showed an association between qEEG power and hyperactivity in younger children with ADHD, while theta activity in the frontal region correlated positively with hyperactivity. The qEEG power of children with ADHD decreased gradually as age increased, and these changes were related to their symptoms. This pilot study suggests that qEEG differences between children with ADHD and healthy children may serve as a sensitive diagnostic tool, depending on the child's age. Further research building upon these findings could deepen our understanding of ADHD and its neural correlates.
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Affiliation(s)
- Nezla S Duric
- Department of Child and Adolescent Psychiatry, Fonna Health Trust, Haugesund, Norway
- Department of Research and Innovation, Fonna Health Trust, Haugesund, Norway
| | - Jørg Assmus
- Centre for Clinical Research, Helse Bergen, Bergen, Norway
| | - Helge Børresen
- Department of Research and Innovation, Fonna Health Trust, Haugesund, Norway
| | | | - Dobrinko Socanski
- Department of Child and Adolescent Psychiatry, Østfold Trust, Fredrikstad, Norway
| | - Armand Duric
- University Hospital Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Tanju Surmeli
- Living Health Center for Research and Education, Istanbul, Turkey
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Zhang R, Li H. Effect of vigorous-intensity exercise on the working memory and inhibitory control among children with attention deficit hyperactivity disorder: a systematic review and meta-analysis. Ital J Pediatr 2025; 51:104. [PMID: 40156018 PMCID: PMC11951569 DOI: 10.1186/s13052-025-01924-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 03/09/2025] [Indexed: 04/01/2025] Open
Abstract
This study primarily evaluated the effects of vigorous-intensity exercises on working memory and inhibitory control in children with attention deficit hyperactivity disorder (ADHD). Search for eligible studies through four databases, and then proceed with screening. The inclusion criteria are as follows: (1) Children with ADHD; (2) Randomised controlled trial; (3) The intervention group received exercise, while the control group did not perform any exercises as the treatment; (4) Conducted pre- and post-exercise assessments, which include working memory and inhibitory control parameters. Use the Cochrane bias risk assessment tool to evaluate the quality of the selected study. Select standardized mean difference as the appropriate effect scale index, and use Revman 5.4 software to analyze the mean difference. This study was registered in the PROSPERO (CRD42024597510). A total of ten studies fulfilled the inclusion criteria and were selected for the meta-analysis. The included studies involved 367 males and 159 females, where 273 belonged to the exercise group and 253 from the control group. Participants in the exercise group enhanced working memory [0.37 (0.12, 0.63) p < 0.05, I2 = 0%] than the control group. In addition, the results indicated that submaximal intensity exercise improved inhibition regulation levels significantly [- 0.34 (- 0.65, - 0.03), p < 0.05, I2 = 0%]. Based on the systematic meta-analysis results, vigorous-intensity exercises have effective working memory, cognitive function, and motor ability-increasing effects on children with ADHD. Furthermore, Submaximal intensity exercise can effectively improve control inhibition in children with ADHD.
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Affiliation(s)
- Ruiyun Zhang
- School of Sport Art, Shandong Sport University, Lichen District, Jinan, 250102, Shandong, China
| | - Haixia Li
- School of Sport Management, Shandong Sport University, Lichen District, Jinan, 250102, Shandong, China.
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Sun XL, Cui J, Bai H, Zhang W, Bai WJ. Aniracetam Ameliorates Attention Deficit Hyperactivity Disorder Behavior in Adolescent Mice. eNeuro 2025; 12:ENEURO.0578-24.2025. [PMID: 40118526 PMCID: PMC11927935 DOI: 10.1523/eneuro.0578-24.2025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 02/09/2025] [Accepted: 02/25/2025] [Indexed: 03/23/2025] Open
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 8-12% of children globally. Hyperactivity-related behaviors, as well as inattention and impulsivity, are regarded as the nuclear symptoms of ADHD. At present, its etiologies and risk factors are unknown. Previous research linked TARP γ-8 deficiency to ADHD-like behaviors in mice, including hyperactivity, impulsivity, and memory deficits. Aniracetam, a nootropic drug, enhances cognition by modulating cholinergic activity and glutamate receptors, offering neuroprotective effects. This study examined TARP γ-8 knockout (KO) mice at 4 and 8 weeks, assessing behaviors through locomotor activity, cliff avoidance, novel object recognition, and contextual fear conditioning tests. TARP γ-8 KO mice exhibited hyperactivity, reduced recognition memory, and impaired short-term memory and long-term memory. Aniracetam administration improved these behavioral deficits, suggesting its potential as a therapeutic agent for ADHD. The findings align with ADHD's pathophysiology, resembling the neurological impairments in TARP γ-8 KO mice. Aniracetam shows promise as a novel treatment for ADHD symptoms, highlighting its therapeutic value.
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Affiliation(s)
- Xiao-Li Sun
- Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei 050017, China
| | - Jie Cui
- College of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei 050017, China
- Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei 050051, China
| | - Hui Bai
- The second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China
| | - Wei Zhang
- Department of Pharmacology, Institution of Chinese Integrative Medicine, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei 050017, China
| | - Wan-Jun Bai
- Department of Pharmacy, Hebei General Hospital, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei 050051, China
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Shafiullah S, Dhaneshwar S. Current Perspectives on Attention-deficit Hyperactivity Disorder. Curr Mol Med 2025; 25:289-304. [PMID: 37221690 DOI: 10.2174/1566524023666230522145950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 02/19/2023] [Accepted: 02/28/2023] [Indexed: 05/25/2023]
Abstract
Attention-deficit hyperactivity disorder (ADHD) is a neurobiological and neurodevelopmental disorder with an idiosyncratic genetic base. ADHD presents various characteristics, such as inattention, hyperactivity, and impulsivity. Over the period, ADHD leads to noticeable functional disability. A five- to ten-fold progressed risk of disorder development is observed in the populations with familial history of ADHD. The abnormal structure of the brain in ADHD results in altered neural mechanisms, such as cognition, attention, and memorial function. The mesolimbic, nigrostriatal, and mesocortical pathways in the brain get affected by the deterioration of the levels of dopamine. The hypothesis of dopamine in ADHD and its etiopathology suggests that detained attention and impaired arousal functions are due to reduced levels of dopamine. The quickest way to improve strategical treatment is by clarifying the etiological aspects of ADHD and identifying the underlying mechanisms of pathophysiology, which will assist in exploring the biomarkers for better diagnosis. The implementation of life course theory is a very important research principle announced by Grand Challenges in Global Health Initiative (GCMHI). Long-term research is needed to define the progression of ADHD. Interdisciplinary collaborations promise a great future for research innovations in ADHD.
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Affiliation(s)
- Shaik Shafiullah
- Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh, Sector 125, Noida, U.P., India
| | - Suneela Dhaneshwar
- Department of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Amity University Maharashtra, Mumbai, Maharashtra, India
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Rosenau PT, Dietrich A, van den Hoofdakker BJ, Hoekstra PJ. ADHD medication adherence reduces risk of committing minor offenses in adolescents. J Child Psychol Psychiatry 2024; 65:1478-1485. [PMID: 38700112 DOI: 10.1111/jcpp.13997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/06/2024] [Indexed: 05/05/2024]
Abstract
BACKGROUND This study aimed to investigate the association between adolescents' adherence to attention-deficit/hyperactivity disorder (ADHD) medication and their risk of committing minor offenses. METHODS Using two Dutch databases, Statistics Netherlands (CBS) and the Foundation for Pharmaceutical Statistics (SFK), we aimed to investigate the association between adherence to ADHD medication and registered minor offenses between 2005 and 2019 of 18,234 adolescents (12-18 years). We used Cox regression analyses to compare the rate of committing minor offenses of adolescents during periods of high ADHD medication adherence compared to periods of low adherence (i.e., periods with or without sufficient amounts of dispensed medication). We additionally tested associations with adherence to selective serotonin reuptake inhibitors (SSRIs) as control medication and analyzed potential reverse causation. RESULTS High ADHD medication adherence was associated with a reduced risk of committing a minor offense of between 33% and 38% compared to low adherence periods of ≥3 months (hazard ratio [HR] 0.67, confidence interval [CI] 0.64-0.71) or ≥6 months (HR 0.62, CI 0.59-0.65). The reduction in risk can likely be attributed to ADHD medication, given the absence of effects of SSRIs and no reverse causation. The reduction rate remained between 16% and 55% per sex, stimulant versus non-stimulant medication, different offense categories and further sensitivity analyses. CONCLUSIONS Among adolescents using ADHD medication, rates of criminality were lower during periods of high medication adherence, suggesting that adherence to ADHD medication may contribute to prevention of minor offenses in adolescents.
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Affiliation(s)
- Paul T Rosenau
- Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Accare Child Study Center, Groningen, The Netherlands
| | - Andrea Dietrich
- Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Accare Child Study Center, Groningen, The Netherlands
| | - Barbara J van den Hoofdakker
- Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Accare Child Study Center, Groningen, The Netherlands
| | - Pieter J Hoekstra
- Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Accare Child Study Center, Groningen, The Netherlands
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Lenartowicz A, DeSchepper B, Simpson GV. Training of Awareness in ADHD: Leveraging Metacognition. JOURNAL OF PSYCHIATRY AND BRAIN SCIENCE 2024; 9:e240006. [PMID: 39493272 PMCID: PMC11529823 DOI: 10.20900/jpbs.20240006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
Abstract
Attention deficit hyperactivity disorder (ADHD) is a disorder that is prevalent in children and adults, with significant impact on life outcomes. Common treatment strategies include a combination of pharmacological and psychosocial interventions which have recognized limits to their effectiveness. Consequently, there exists interest in additional non-pharmacological interventions. In the current minireview we aim to complement existing surveys by focusing on a complementary approach, namely rooted in metacognition or the training of awareness. We review programs that incorporate metacognitive training of awareness in skill-training, psychosocial interventions, and mindfulness, and discuss existing assessments of metacognitive ability in ADHD. Existing data suggest that metacognitive approaches have potential in supporting symptom management in ADHD, with gains in objective assessments in near and far transfer tasks in educational research and high satisfaction from parents. Further research is warranted in assessment of the relative contribution of metacognitive elements relative to other treatment components, objective assessments of outcomes in psychosocial interventions, and efficacy in adult interventions.
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Affiliation(s)
- Agatha Lenartowicz
- Department of Psychiatry & Biobehavioral Sciences, OneMind Staglin Center for Cognitive Neuroscience, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA
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D’Aiello B, Di Vara S, De Rossi P, Vicari S, Menghini D. The effect of a single dose of methylphenidate on attention in children and adolescents with ADHD and comorbid Oppositional Defiant Disorder. PLoS One 2024; 19:e0299449. [PMID: 39133690 PMCID: PMC11318934 DOI: 10.1371/journal.pone.0299449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 02/10/2024] [Indexed: 08/15/2024] Open
Abstract
The co-occurrence Oppositional Defiant Disorder (ODD) in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) has been associated to difficulties in regulating adverse states, elevated functional impairment, deficits in Executive Functions and high risk for psychopathology. Recent studies have shown that ODD is a negative predictor of a positive response to methylphenidate (MPH) treatment for ADHD symptoms in children and adolescents and that patients with a diagnosis of comorbid ADHD and ODD are less likely to respond favorably to pharmacological treatment with MPH. We conducted a naturalistic study to understand the clinical characteristics of drug-naïve children and adolescents with ADHD that influence the response to MPH by measuring the effect on attention. Specifically, we investigated whether a single dose of MPH differently affects the performance of 53 children and adolescents with ADHD with or without ODD comorbidity. In addition, participant characteristics such as symptom severity, functional impairment, and associated behavioral and emotional symptoms at baseline were examined to better understand what aspects affect the response to MPH. We found that a single dose of MPH improved the attention of children and adolescents with ADHD without ODD more than those with comorbid ADHD and ODD, resulting in reduced reaction times. Our findings indicated that children and adolescents with comorbid ADHD and ODD and those with ADHD alone did not exhibit differences in measures of attention prior to taking MPH, nor in demographic variables (age, intelligence quotient, gender), clinical characteristics related to symptom severity, and adaptive behaviors. However, we observed differences between the two groups in certain behavioral aspects, including the Dysregulation Profile and disruptive behaviors. Assessing symptoms in combination with the presence of ADHD can be beneficial in determining which individuals would derive the greatest benefits from treatment.
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Affiliation(s)
- Barbara D’Aiello
- Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
- Department of Human Science, LUMSA University, Rome, Italy
| | - Silvia Di Vara
- Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Pietro De Rossi
- Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Stefano Vicari
- Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
- Department of Life Science and Public Health, Catholic University of the Sacred Heart, Rome, Italy
| | - Deny Menghini
- Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
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Wu F, Zhang W, Ji W, Zhang Y, Jiang F, Li G, Hu Y, Wei X, Wang H, Wang SYA, Manza P, Tomasi D, Volkow ND, Gao X, Wang GJ, Zhang Y. Stimulant medications in children with ADHD normalize the structure of brain regions associated with attention and reward. Neuropsychopharmacology 2024; 49:1330-1340. [PMID: 38409281 PMCID: PMC11224385 DOI: 10.1038/s41386-024-01831-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/30/2024] [Accepted: 02/09/2024] [Indexed: 02/28/2024]
Abstract
Children with ADHD show abnormal brain function and structure. Neuroimaging studies found that stimulant medications may improve brain structural abnormalities in children with ADHD. However, prior studies on this topic were conducted with relatively small sample sizes and wide age ranges and showed inconsistent results. In this cross-sectional study, we employed latent class analysis and linear mixed-effects models to estimate the impact of stimulant medications using demographic, clinical measures, and brain structure in a large and diverse sample of children aged 9-11 from the Adolescent Brain and Cognitive Development Study. We studied 273 children with low ADHD symptoms and received stimulant medication (Stim Low-ADHD), 1002 children with high ADHD symptoms and received no medications (No-Med ADHD), and 5378 typically developing controls (TDC). After controlling for the covariates, compared to Stim Low-ADHD and TDC, No-Med ADHD showed lower cortical thickness in the right insula (INS, d = 0.340, PFDR = 0.003) and subcortical volume in the left nucleus accumbens (NAc, d = 0.371, PFDR = 0.003), indicating that high ADHD symptoms were associated with structural abnormalities in these brain regions. In addition, there was no difference in brain structural measures between Stim Low-ADHD and TDC children, suggesting that the stimulant effects improved both ADHD symptoms and ADHD-associated brain structural abnormalities. These findings together suggested that children with ADHD appear to have structural abnormalities in brain regions associated with saliency and reward processing, and treatment with stimulant medications not only improve the ADHD symptoms but also normalized these brain structural abnormalities.
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Affiliation(s)
- Feifei Wu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Wenchao Zhang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Weibin Ji
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Yaqi Zhang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Fukun Jiang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Guanya Li
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Yang Hu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China
| | - Xiaorong Wei
- Kindergarten affiliated to Air Force Medical University, Xi'an, Shaanxi, 710032, China
| | - Haoyi Wang
- College of Westa, Southwest University, Chongqing, 400715, China
| | - Szu-Yung Ariel Wang
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA
| | - Peter Manza
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA
| | - Dardo Tomasi
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA
| | - Nora D Volkow
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA
| | - Xinbo Gao
- Chongqing Key Laboratory of Image Cognition, Chongqing University of Posts and Telecommunications, Chongqing, 400065, China
- Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, 400064, China
| | - Gene-Jack Wang
- Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
| | - Yi Zhang
- Center for Brain Imaging, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, 710126, China.
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
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Elmaghraby R, Pines A, Geske JR, Coombes BJ, Leung JG, Croarkin PE, Markota M, Bobo WV. Risk of Newly Diagnosed Psychotic Symptoms in Youth Receiving Medications for Attention-Deficit/Hyperactivity Disorder. JAACAP OPEN 2024; 2:135-144. [PMID: 39554204 PMCID: PMC11562438 DOI: 10.1016/j.jaacop.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/29/2024] [Indexed: 11/19/2024]
Abstract
Objective Epidemiological studies suggest that patients with attention-deficit/hyperactivity disorder (ADHD) treated with amphetamines have an increased risk of newly diagnosed psychosis. This risk in youth is poorly understood. This investigation studied the potential risk of newly diagnosed psychotic symptoms associated with exposure to 4 classes of ADHD medications. Method This retrospective study used a medical records-linkage system from a cohort of youth (age 6-18 years) with diagnosed ADHD who were prescribed amphetamines, methylphenidate, atomoxetine, or α-2 agonists. Cohort members with any diagnosis of psychosis before their first ADHD medication were excluded. The primary outcome was newly diagnosed psychotic symptoms. The risk for psychotic symptoms for each medication (vs the remaining medication classes combined) was estimated using a multivariable time-varying covariate Cox proportional hazard regression model that adjusted for sex and age at ADHD diagnosis. Results Of 5,171 youth (68.6% male), 134 (2.6 %) had newly diagnosed psychotic symptoms. Exposure to amphetamine (vs amphetamine nonexposure, hazard ratio 1.41, 95% CI 1.15-2.26) and atomoxetine (vs atomoxetine nonexposure, hazard ratio 2.01, 95% CI 1.38-2.92) was associated with increased risk of newly diagnosed psychotic symptoms. Secondary analysis showed that the frequency of newly diagnosed psychotic symptoms was higher with atomoxetine/stimulant lifetime combination therapy (12.5% with amphetamines, 7.7% with methylphenidate) than atomoxetine monotherapy (1.2%). Conclusion Risk of newly diagnosed psychotic symptoms was low. These results suggest that cumulative exposure to amphetamines or atomoxetine/stimulant lifetime combination therapy may be associated with an increased risk of newly diagnosed psychotic symptoms in youth with ADHD. Diversity & Inclusion Statement We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
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Affiliation(s)
- Rana Elmaghraby
- Cincinnati Children’s Hospital Medical Center. Cincinnati, Ohio
| | - Andrew Pines
- Bringham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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Hrabarchuk EI, Hannah T, Kalagara R, Li AY, Schupper AJ, McCarthy L, Ali M, Quinones A, Gometz A, Lovell M, Choudhri TF. Baseline ImPACT Composite Scores in Student-Athletes With Attention-Deficit/Hyperactivity Disorder. Arch Clin Neuropsychol 2024; 39:347-354. [PMID: 37824213 DOI: 10.1093/arclin/acad076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 10/14/2023] Open
Abstract
BACKGROUND Athletes who are diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of concussion compared to other athletes. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a widely used concussion tool, but it relies on pre-injury baseline testing that can be affected by psychiatric conditions. This research aims to determine if there are differences in pre-injury testing composite scores in student-athletes with ADHD compared to those without ADHD diagnosis. METHODS We obtained 11,563 pre-season ImPACT assessments of 7,454 student-athletes (ages: 12-22) from 2009 to 2019. After exclusions, there were 6,920 control and 276 ADHD subjects. Multivariable linear regression analyses compared the independent effect of ADHD on the six ImPACT composite score metrics with Bonferroni correction for multiple comparisons with a = 0.008. RESULTS Univariate analyses indicated ADHD is associated with more symptoms as measured by the Post-Concussion Symptom Scale (PCSS) (β = 2.67, 95% CI: 1.47-3.87, p < .0001) and worse Impulse Control scores (β = 0.93, 95% CI: 0.33-1.53, p = .002). In multivariate analysis, this association was the same for symptom score (β = 2.48, 95% CI: 1.22-3.74, p < .0001), but Impulse Control was not significantly different after multiple comparison adjustment (β = 0.87, 95% CI: 0.22-1.15, p = .009). CONCLUSIONS The ADHD subjects reported worse symptoms at baseline and had worse Impulse Control in univariate analysis, but not multivariate analysis. These results can further guide clinicians in concussion diagnosis and test interpretations for student-athletes with ADHD, considering the symptom burden at baseline.
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Affiliation(s)
- Eugene I Hrabarchuk
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Theodore Hannah
- Department of Neurosurgery, Lewis Katz School of Medicine Temple University, Philadelphia, PA, USA
| | - Roshini Kalagara
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Adam Y Li
- Department of Neurosurgery, University of Rochester School of Medicine, New York, NY, USA
| | - Alexander J Schupper
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Lily McCarthy
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Muhammad Ali
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Addison Quinones
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Alex Gometz
- Physical Medicine and Rehabilitation, Concussion Management of New York, NY, USA
| | - Mark Lovell
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Tanvir F Choudhri
- Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Zare Dehnavi A, Elmitwalli I, Alsharif HOH, Shervin Razavi A, Gumpel TA, Smith A, Weinstock RS, Faraone SV, Zhang-James Y. Effects of ADHD and ADHD treatment on glycemic management in type 1 diabetes: A systematic review and meta-analysis of observational studies. Diabetes Res Clin Pract 2024; 209:111566. [PMID: 38360095 DOI: 10.1016/j.diabres.2024.111566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/11/2023] [Accepted: 02/04/2024] [Indexed: 02/17/2024]
Abstract
AIMS Studies suggested a higher prevalence of Attention-deficit/hyperactivity disorder (ADHD) in individuals with Type 1 Diabetes Mellitus (T1D). However, it is unclear how ADHD impacts glycemia and diabetes-related complications. This systematic review and meta-analysis aimed to investigate the effect of ADHD and ADHD medications on HbA1c and acute complications in T1D. METHODS A literature search was conducted in PubMed, EMBASE, CINAHL, Scopus, PsycINFO, CENTRAL, and Web of Science collections up to November 22, 2023. Seventeen studies were selected for the systematic review by independent reviewers, with twelve included in the meta-analysis. RESULTS Mean HbA1c levels were significantly higher in T1D individuals with ADHD compared to those without ADHD (MD = 0.60; 95 % CI: 0.41, 0.79; I2 = 90.1 %; p-value < 0.001). The rates of suboptimal HbA1c levels, hospitalization, diabetic ketoacidosis, and hypoglycemia were all substantially higher in T1D individuals with ADHD than those without ADHD. No difference was found in mean HbA1c between those who received ADHD treatment and those who did not (mean difference = -0.52; 95 % confidence interval: -1.16, 0.13; I2 = 78.6 %; p-value = 0.12). CONCLUSIONS ADHD is associated with higher HbA1c and increased acute diabetes-related complications. More research is needed to assess the effects of ADHD treatments on T1D management.
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Affiliation(s)
- Ali Zare Dehnavi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine & Science, Rochester, MN 55905, USA; School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran
| | - Islam Elmitwalli
- Nationwide Children's Hospital, Department of Anesthesiology and Pain Medicine, 700 Children's Drive, Columbus, OH 43205, USA
| | - Hisham O H Alsharif
- Mansoura University Hospital, El Mansoura, Dakahlia Governorate 7650030, Egypt
| | - Ali Shervin Razavi
- Norton College of Medicine, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Tyler A Gumpel
- Norton College of Medicine, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Abigail Smith
- Health Sciences Library, Norton College of Medicine at SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Ruth S Weinstock
- Division of Endocrinology, Diabetes and Metabolism, Norton College of Medicine at SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA; Department of Medicine, Norton College of Medicine at SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Stephen V Faraone
- Department of Psychiatry & Behavioral Sciences, Norton College of Medicine at SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA; Department of Neuroscience and Physiology, Norton College of Medicine at SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
| | - Yanli Zhang-James
- Department of Psychiatry & Behavioral Sciences, Norton College of Medicine at SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
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12
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Adler LA, Anbarasan D, Sardoff T, Leon T, Gallagher R, Massimi CA, Faraone SV. A Single-Blind, Placebo Controlled Trial of Triple Beaded Mixed Amphetamine Salts in DSM-5 Adults With ADHD Assessing Effects Throughout the Day. J Atten Disord 2024; 28:810-819. [PMID: 38214178 DOI: 10.1177/10870547231222260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
OBJECTIVE To examine the effects of triple beaded mixed amphetamine salts (TB MAS) on ADHD and executive dysfunction symptoms throughout the day in adults with DSM-5 ADHD. METHOD This was a 6 week, single-blind, placebo-lead in trial of TB MAS (12.5-37.5 mg/day); all participants received 2 weeks of single-blind placebo); one individual was a placebo responder and was discontinued. One of these 18 dropped after 1 week on 12.5 mg/day, while all others completed the trial and received 37.5 mg/day TB MAS. RESULTS There were significant effects of TB MAS on all clinical measures, including investigator overall symptoms (AISRS); self-report overall (ASRS), time-sensitive ADHD (TASS) scores throughout the day, impairment (CGI) and executive function scores (BRIEF-A). TB MAS was generally well tolerated. CONCLUSIONS This study extends prior findings of TB MAS to adults with DSM-5 ADHD; it further re-validates findings of efficacy of TB MAS throughout the day.
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13
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Wojciechowski T. Understanding the Impact of Deviant Peer Association on Dual Systems Model Development: Testing the Moderating Role of ADHD. J Nerv Ment Dis 2024; 212:96-103. [PMID: 37983371 DOI: 10.1097/nmd.0000000000001743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
ABSTRACT Recent research has indicated that deviant peers may play a role in cognitive development. This is particularly the case for the dual systems model, a key framework for understanding engagement in antisocial behavior during adolescence and emerging adulthood. However, limited research has examined how preexisting mental health concerns may moderate these relationships. This study used the Pathways to Desistance data to examine attention deficit hyperactivity disorder (ADHD) as a moderator of the relationships between deviant peer association and dual systems model constructs. Generalized estimating equations were used to test these relationships. Results indicated that deviant peer association and the presence of ADHD both predicted increased sensation-seeking and lower impulse control. ADHD significantly moderated the relationship between deviant peer association and impulse control, indicating a weaker impact of deviant peer association on impulse control among participants with ADHD. No significant interaction was observed for the relationship between deviant peer association and sensation-seeking.
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14
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Kaiser A, Aggensteiner PM, Blasco Fontecilla H, Ros T, Acquaviva E, Attal Y, Banaschewski T, Baumeister S, Bousquet E, Bussalb A, Delhaye M, Delorme R, Drechsler R, Goujon A, Häge A, Mayaud L, Mechler K, Menache C, Revol O, Tagwerker F, Walitza S, Werling AM, Bioulac S, Purper-Ouakil D, Brandeis D. Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD. Front Psychiatry 2024; 14:1331004. [PMID: 38312916 PMCID: PMC10836215 DOI: 10.3389/fpsyt.2023.1331004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/29/2023] [Indexed: 02/06/2024] Open
Abstract
Introduction Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers. Methods Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response. Results For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only. Discussion Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.
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Affiliation(s)
- Anna Kaiser
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Pascal M Aggensteiner
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | | | - Tomas Ros
- Department of Neuroscience, Campus Biotech CISA-Université de Genève, Genève, Switzerland
| | - Eric Acquaviva
- Child and Adolescent Psychiatry Department and Child Brain Institute, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris and Universite Paris Cite, Paris, France
| | | | - Tobias Banaschewski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Sarah Baumeister
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | - Elisa Bousquet
- Unit of Child and Adolescent Psychiatry (MPEA1), CHU Montpellier-Saint Eloi Hospital, University of Montpellier, Montpellier, France
| | | | - Marie Delhaye
- Child and Adolescent Psychiatry, Erasme Academic Hospital, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Richard Delorme
- Child and Adolescent Psychiatry Department and Child Brain Institute, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris and Universite Paris Cite, Paris, France
| | - Renate Drechsler
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
| | - Allison Goujon
- Unit of Child and Adolescent Psychiatry (MPEA1), CHU Montpellier-Saint Eloi Hospital, University of Montpellier, Montpellier, France
| | - Alexander Häge
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | | | - Konstantin Mechler
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
| | | | - Olivier Revol
- Unit of Child and Adolescent Psychiatry, Hospices civils de Lyon, Hôpital Femme Mère Enfant, Bron Cedex, France
| | - Friederike Tagwerker
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
| | - Susanne Walitza
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
| | - Anna Maria Werling
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
| | - Stéphanie Bioulac
- SANPSY, USR 3413, CNRS, Bordeaux, France
- Clinique du Sommeil, CHU Pellegrin, Bordeaux Cedex, France
| | - Diane Purper-Ouakil
- Unit of Child and Adolescent Psychiatry (MPEA1), CHU Montpellier-Saint Eloi Hospital, University of Montpellier, Montpellier, France
- Development and Trajectories, INSERM CESP U 1018 Psychiatry, Montpellier, France
- CESP, INSERM U 1018, Paul Brousse Hospital, Villejuif, France
| | - Daniel Brandeis
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
- Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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15
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Lee CSC, Chen TT, Gao Q, Hua C, Song R, Huang XP. The Effects of Theta/Beta-based Neurofeedback Training on Attention in Children with Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis. Child Psychiatry Hum Dev 2023; 54:1577-1606. [PMID: 35471754 DOI: 10.1007/s10578-022-01361-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/01/2022] [Indexed: 11/25/2022]
Abstract
Neurofeedback training is a common treatment option for attention deficit hyperactivity disorder (ADHD). Given theta/beta-based neurofeedback (T/B NF) training targets at the electrophysiological characteristics of children with ADHD, benefits for attention may be expected. PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science were searched through December 31, 2020. Studies were evaluated with Risk of Bias tools. Within-group effects based on Pre- and Post-treatment comparisons of the Intervention Group, and Between-group effects based on the between-group differences from Pre-treatment to Post-treatment were calculated. Nineteen studies met selection criteria for systematic review, 12 of them were included in meta-analysis. Within-group effects were medium at Post-treatment and large at Follow-up. Between-group analyses revealed that T/B NF was superior to waitlist control and physical activities, but not stimulant medication. Results showed that T/B NF has benefits for attention in children with ADHD, however, cautions should be taken when interpreting the findings.
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Affiliation(s)
- Clara S C Lee
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
| | - Ting-Ting Chen
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
| | - Qingwen Gao
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
| | - Chunzhuo Hua
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
| | - Rui Song
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
| | - Xiu-Ping Huang
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
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16
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Weerkamp PMM, Geuens S, Collin P, Goemans N, Vermeulen RJ, De Waele L, Hendriksen JGM, Klinkenberg S. Psychopharmaceutical treatment for neurobehavioral problems in Duchenne muscular dystrophy: a descriptive study using real-world data. Neuromuscul Disord 2023; 33:619-626. [PMID: 37453172 DOI: 10.1016/j.nmd.2023.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 05/08/2023] [Accepted: 05/31/2023] [Indexed: 07/18/2023]
Abstract
Patients with Duchenne muscular dystrophy (DMD) are at risk to develop neurobehavioral problems. Evidence on how to treat these difficulties is scarce. This descriptive study reports the clinical experience with psychopharmaceutical treatment in 52 patients with DMD. Electronic patient files were searched for patients with DMD that had been treated with psychopharmaceuticals between 2008 and 2022. Information about neurobehavioral symptoms, type of medication, side effects, and behavioral changes were collected. Two independent clinicians used the clinical global impression scale (CGI) to assess severity of the neurobehavioral problems before and the change in symptoms after treatment. Descriptive statistics were used. Our results include 52 males with DMD (mean age 11 years) treated with psychopharmaceuticals of which 55.8% had four or more comorbid neurobehavioral symptoms. The clinical condition was much improved on the GCI in 54.2% treated with methylphenidate, in 38.9% of the patients treated with fluoxetine, and in 22.2% treated with risperidone. Minimal effects and side effects were also reported. In conclusion, patients with DMD may experience severe neurobehavioral symptoms interfering with learning and/or development. Treatment with psychopharmaceuticals can improve these neurobehavioral symptoms, but further research is needed to gain better insights in psychopharmaceutical treatment in patients with DMD.
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Affiliation(s)
- Pien M M Weerkamp
- Kempenhaege, Centre for Neurological Learning Disabilities, Heeze, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
| | - Sam Geuens
- Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Philippe Collin
- Kempenhaege, Centre for Neurological Learning Disabilities, Heeze, the Netherlands; Department of Child and Adolescent Psychiatry, Koraal, Sittard, the Netherlands
| | - Nathalie Goemans
- Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium
| | - R Jeroen Vermeulen
- Department of Neurology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Liesbeth De Waele
- Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium
| | - Jos G M Hendriksen
- Kempenhaege, Centre for Neurological Learning Disabilities, Heeze, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Department of Neurology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Sylvia Klinkenberg
- Kempenhaege, Centre for Neurological Learning Disabilities, Heeze, the Netherlands; Department of Neurology, Maastricht University Medical Centre, Maastricht, the Netherlands
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17
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Hellings J. Pharmacotherapy in autism spectrum disorders, including promising older drugs warranting trials. World J Psychiatry 2023; 13:262-277. [PMID: 37383284 PMCID: PMC10294139 DOI: 10.5498/wjp.v13.i6.262] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/06/2023] [Accepted: 04/18/2023] [Indexed: 06/19/2023] Open
Abstract
Available pharmacotherapies for autism spectrum disorders (ASD) are reviewed based on clinical and research experience, highlighting some older drugs with emerging evidence. Several medications show efficacy in ASD, though controlled studies in ASD are largely lacking. Only risperidone and aripiprazole have Federal Drug Administration approval in the United States. Methylphenidate (MPH) studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder (ADHD) than in the typically developing (TD) population; atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes. Guanfacine improved hyperactivity in ASD comparably to TD. Dex-troamphetamine promises greater efficacy than MPH in ASD. ADHD medications reduce impulsive aggression in youth, and may also be key for this in adults. Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors. Trials of antiseizure medications in ASD remain inconclusive, however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors. No identified drugs treat ASD core symptoms; oxytocin lacked efficacy. Amitriptyline and loxapine however, show promise. Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies, but may be weight-sparing. Amitriptyline at approximately 1 mg/ kg/day used cautiously, shows efficacy for sleep, anxiety, impulsivity and ADHD, repetitive behaviors, and enuresis. Both drugs have promising neurotrophic properties.
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Affiliation(s)
- Jessica Hellings
- Department of Psychiatry, University of Missouri-Kansas City, Lee's Summit, MO 64063, United States
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18
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Seok JW, Soltis-Vaughan B, Lew BJ, Ahmad A, Blair RJR, Hwang S. Psychopharmacological treatment of disruptive behavior in youths: systematic review and network meta-analysis. Sci Rep 2023; 13:6921. [PMID: 37117632 PMCID: PMC10147946 DOI: 10.1038/s41598-023-33979-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 04/21/2023] [Indexed: 04/30/2023] Open
Abstract
To conduct a systematic review of the comparative efficacy of various psychotropic medications for the treatment of disruptive behavior (DBs) in youths. To this aim, we systematically reviewed randomized clinical trials (RCTs) of various psychotropic medications targeting symptoms of DBs and applied network meta-analysis to investigate their relative efficacy. Fifty-five RCTs meeting the inclusion criteria were selected. To predict and interpret relative treatment efficacy, we compared the efficacy of various psychotropic medications prescribed for DB symptoms based on their mechanism of action. Network meta-analysis revealed that for reducing DBs, second-generation antipsychotics, stimulants, and non-stimulant ADHD medications were more efficacious than placebo, and second-generation antipsychotics were the most efficacious. The dopaminergic modulation of top-down inhibitory process by these medications is discussed in this review. This study offers information on the relative efficacy of various psychotropic medications for the treatment of DB, and insight into a potential neurobiological underpinning for those symptoms. It also illustrates the potential utility of these neurobiological mechanisms as a target for future treatment studies.
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Affiliation(s)
- Ji-Woo Seok
- Department of Psychiatry, University of Nebraska Medical Center, 985578 Nebraska Medical Center, Omaha, NE, 68198-5578, USA
- Digital Health Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
| | - Brigette Soltis-Vaughan
- Department of Psychiatry, University of Nebraska Medical Center, 985578 Nebraska Medical Center, Omaha, NE, 68198-5578, USA
| | - Brandon J Lew
- Department of Psychiatry, University of Nebraska Medical Center, 985578 Nebraska Medical Center, Omaha, NE, 68198-5578, USA
| | - Aatiya Ahmad
- Department of Psychiatry, University of Nebraska Medical Center, 985578 Nebraska Medical Center, Omaha, NE, 68198-5578, USA
| | - R J R Blair
- Child and Adolescent Mental Health Centre, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark
| | - Soonjo Hwang
- Department of Psychiatry, University of Nebraska Medical Center, 985578 Nebraska Medical Center, Omaha, NE, 68198-5578, USA.
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Ziv-Baran T, Zacay G, Modan-Moses D, Reingold SM, Mekori E, Levy-Shraga Y. Increased fracture risk among children diagnosed with attention- deficit/hyperactivity disorder: a large matched cohort study. Eur J Pediatr 2023:10.1007/s00431-023-04929-x. [PMID: 37004585 DOI: 10.1007/s00431-023-04929-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 03/03/2023] [Accepted: 03/06/2023] [Indexed: 04/04/2023]
Abstract
To analyse the risk of fractures among children with attention-deficit/hyperactivity disorder (ADHD) compared with matched children without ADHD; and to evaluate the impact of pharmacological treatment. This registry-based cohort study included 31,330 children diagnosed with ADHD and a comparison group of 62,660 children matched by age, sex, population sector and socioeconomic status. Demographic and clinical information was extracted from the electronic database of Meuhedet, a health maintenance organization. Fracture events between 2-18 years of age were identified by coded diagnoses. The overall fracture incidence rate was 334 per 10,000 patient-years (PY) in the ADHD group and 284 per 10,000 PY in the comparison group (p < 0.001). Among boys, the fracture incidence rates were 388 per 10,000 PY and 327 per 10,000 PY (p < 0.001), for the respective groups. Among girls, the rates were lower in both groups compared to boys, but higher in the ADHD compared to the matched group (246 vs 203 per 10,000 PY, p < 0.001). Among the children with ADHD, the hazard ratios (HR) to have a fracture were similar in boys (1.18, 95%CI 1.15-1.22, p < 0.001) and girls (1.22, 95%CI 1.16-1.28, p < 0.001). Children with ADHD were also at increased risk for two and three fractures; the hazard ratios (HRs) were 1.32 (95%CI 1.26-1.38, p < 0.001) and 1.35 (95%CI 1.24-1.46, p < 0.001), respectively. In a multivariable model of the children with ADHD, pharmacological treatment was associated with reduced fracture risk (HR 0.90, 95%CI 0.82-0.98, p < 0.001) after adjustment for sex, resident socioeconomic status and population sector. Conclusion: Children with ADHD had greater fracture risk than a matched group without ADHD. Pharmacological treatment for ADHD may decrease this risk. What is Known: • Children with attention-deficit/hyperactivity disorder (ADHD) may be more prone to injuries and fractures than children without ADHD. What is New: • Children with ADHD were 1.2 times more likely to have a fracture than children with similar characteristics, without ADHD. The increased risk for fractures was even greater for two and three fractures (hazard ratios 1.32 and 1.35, respectively). • Our study suggests a positive effect of pharmacological treatment for ADHD in reducing fracture risk.
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Affiliation(s)
- Tomer Ziv-Baran
- School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Galia Zacay
- Meuhedet Health Services, Tel Aviv, Israel
- Sackler School of Medicine, University of Tel Aviv, Tel Aviv, Israel
| | - Dalit Modan-Moses
- Meuhedet Health Services, Tel Aviv, Israel
- Sackler School of Medicine, University of Tel Aviv, Tel Aviv, Israel
- Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Childrens Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Stephen M Reingold
- Meuhedet Health Services, Tel Aviv, Israel
- Sackler School of Medicine, University of Tel Aviv, Tel Aviv, Israel
| | - Ehud Mekori
- Sackler School of Medicine, University of Tel Aviv, Tel Aviv, Israel
- Child and Adolescent Psychiatry Division, The Edmond and Lily Safra Childrens Hospital, Chaim Sheba Medical Center, 52621, Tel-Hashomer, Israel
| | - Yael Levy-Shraga
- Meuhedet Health Services, Tel Aviv, Israel.
- Sackler School of Medicine, University of Tel Aviv, Tel Aviv, Israel.
- Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Childrens Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
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20
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Soufsaf S, Robaey P, Nekka F. An exploratory analysis of the performance of methylphenidate regimens based on a PKPD model of dopamine and norepinephrine transporter occupancy. J Pharmacokinet Pharmacodyn 2023:10.1007/s10928-023-09854-y. [PMID: 36930337 DOI: 10.1007/s10928-023-09854-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 02/23/2023] [Indexed: 03/18/2023]
Abstract
Methylphenidate (MPH) is a psychostimulant which inhibits the uptake of dopamine and norepinephrine transporters, DAT and NET, and is mostly used to treat Attention Deficit/Hyperactivity Disorder. The current dose optimization is done through titration, a cumbersome approach for patients. To assess the therapeutic performance of MPH regimens, we introduce an in silico framework composed of (i) a population pharmacokinetic model of MPH, (ii) a pharmacodynamic (PD) model of DAT and NET occupancy, (iii) a therapeutic box delimited by time and DAT occupancy, and (iv) a performance score computation. DAT occupancy data was digitized (n = 152) and described with Emax models. NET occupancy was described with a KPD model. We used this integrative framework to simulate the performance of extended-release (18-99 mg) and tid MPH regimens (25-40 mg). Early blood samples of MPH seem to lead to higher DAT occupancy, consistent with an acute tolerance observed in clinical rating scales. An Emax model with a time-dependent tolerance was fitted to available data to assess the observed clockwise hysteresis. Peak performance is observed at 63 mg. While our analysis does not deny the existence of an acute tolerance, data precision in terms of formulation and sampling times does not allow a definite confirmation of this phenomenon. This work justifies the need for a more systematic collection of DAT and NET occupancy data to further investigate the presence of acute tolerance and assess the impact of low MPH doses on its efficacy.
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21
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Sifeddine W, Ba-M'hamed S, Landry M, Bennis M. Effect of atomoxetine on ADHD-pain hypersensitization comorbidity in 6-OHDA lesioned mice. Pharmacol Rep 2023; 75:342-357. [PMID: 36787018 DOI: 10.1007/s43440-023-00459-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/26/2023] [Accepted: 01/31/2023] [Indexed: 02/15/2023]
Abstract
BACKGROUND Methylphenidate and atomoxetine are used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Our previous studies established the validity of the 6-hydroxydopamine (6-OHDA) mouse model of ADHD and demonstrated hypersensitivity to pain, in line with clinical reports in ADHD patients. Acute methylphenidate treatment reduces hyperactivity and increases attention, but does not affect pain behaviors in this mouse model. Whereas atomoxetine has been shown to be effective against some symptoms of ADHD, nothing is known about its possible action on comorbid pain hypersensitivity. The objectives of the present research are (1) to investigate the effects of acute and chronic treatment with atomoxetine on ADHD-like symptoms and nociceptive thresholds, and (2) to explore the catecholaminergic systems underlying these effects. METHODS Sham and 6-OHDA cohorts of male mice were tested for hyperactivity (open field), attention and impulsivity (5-choice serial reaction time task test), and thermal (hot plate test) and mechanical (von Frey test) thresholds after acute or repeated treatment with vehicle or atomoxetine (1, 3 or 10 mg/kg). RESULTS Acute administration of atomoxetine (10 mg/kg) reduced the hyperactivity and impulsivity displayed by 6-OHDA mice, without affecting attention or nociception. However, atomoxetine administered at 3 mg/kg/day for 7 days alleviated the ADHD-like core symptoms and attenuated the hyperalgesic responses. Furthermore, hyperlocomotion and anti-hyperalgesic activity were antagonized with phentolamine, propranolol, and sulpiride pre-treatments. CONCLUSION These findings demonstrated that when administered chronically, atomoxetine has a significant effect on ADHD-associated pain hypersensitization, likely mediated by both α- and β-adrenergic and D2/D3 dopaminergic receptors, and suggest new indications for atomoxetine that will need to be confirmed by well-designed clinical trials.
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Affiliation(s)
- Wahiba Sifeddine
- Laboratory of Pharmacology, Neurobiology, Anthropobiology, and Environment, Faculty of Sciences, Cadi Ayyad University, Avenue Prince My Abdellah, B.P. 2390, 40000, Marrakesh, Morocco
| | - Saadia Ba-M'hamed
- Laboratory of Pharmacology, Neurobiology, Anthropobiology, and Environment, Faculty of Sciences, Cadi Ayyad University, Avenue Prince My Abdellah, B.P. 2390, 40000, Marrakesh, Morocco
| | - Marc Landry
- University of Bordeaux, CNRS, Institute of Neurodegenerative Diseases, UMR 5293, Bordeaux, France.,University of Bordeaux, CNRS, INSERM, Bordeaux Imaging Center, UMS 3420, US 4, Bordeaux, France
| | - Mohamed Bennis
- Laboratory of Pharmacology, Neurobiology, Anthropobiology, and Environment, Faculty of Sciences, Cadi Ayyad University, Avenue Prince My Abdellah, B.P. 2390, 40000, Marrakesh, Morocco.
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22
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Hervig MES, Toschi C, Petersen A, Vangkilde S, Gether U, Robbins TW. Theory of visual attention (TVA) applied to rats performing the 5-choice serial reaction time task: differential effects of dopaminergic and noradrenergic manipulations. Psychopharmacology (Berl) 2023; 240:41-58. [PMID: 36434307 PMCID: PMC9816296 DOI: 10.1007/s00213-022-06269-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 10/21/2022] [Indexed: 11/27/2022]
Abstract
RATIONALE Attention is compromised in many psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). While dopamine and noradrenaline systems have been implicated in ADHD, their exact role in attentional processing is yet unknown. OBJECTIVES We applied the theory of visual attention (TVA) model, adapted from human research, to the rat 5-choice serial reaction time task (5CSRTT) to investigate catecholaminergic modulation of visual attentional processing in healthy subjects of high- and low-attention phenotypes. METHODS Rats trained on the standard 5CSRTT and tested with variable stimulus durations were treated systemically with noradrenergic and/or dopaminergic agents (atomoxetine, methylphenidate, amphetamine, phenylephrine and atipamezole). TVA modelling was applied to estimate visual processing speed for correct and incorrect visual perceptual categorisations, independent of motor reaction times, as measures of attentional capacity. RESULTS Atomoxetine and phenylephrine decreased response frequencies, including premature responses, increased omissions and slowed responding. In contrast, methylphenidate, amphetamine and atipamezole sped up responding and increased premature responses. Visual processing speed was also affected differentially. Atomoxetine and phenylephrine slowed, whereas methylphenidate and atipamezole sped up, visual processing, both for correct and incorrect categorisations. Amphetamine selectively improved visual processing for correct, though not incorrect, responses in high-attention rats only, possibly reflecting improved attention. CONCLUSIONS These data indicate that the application of TVA to the 5CSRTT provides an enhanced sensitivity to capturing attentional effects. Unexpectedly, we found overall slowing effects, including impaired visual processing, following drugs either increasing extracellular noradrenaline (atomoxetine) or activating the α1-adrenoceptor (phenylephrine), while also ameliorating premature responses (impulsivity). In contrast, amphetamine had potential pro-attentional effects by enhancing visual processing, probably due to central dopamine upregulation.
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Affiliation(s)
- Mona El-Sayed Hervig
- Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. .,Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
| | - Chiara Toschi
- Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
| | - Anders Petersen
- Department of Psychology, University of Copenhagen, Copenhagen, Denmark
| | - Signe Vangkilde
- Department of Psychology, University of Copenhagen, Copenhagen, Denmark
| | - Ulrik Gether
- Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark
| | - Trevor W. Robbins
- Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
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23
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Idrees I, Bellato A, Cortese S, Groom MJ. The effects of stimulant and non-stimulant medications on the autonomic nervous system (ANS) functioning in people with ADHD: A systematic review and meta-analysis. Neurosci Biobehav Rev 2023; 144:104968. [PMID: 36427764 DOI: 10.1016/j.neubiorev.2022.104968] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 11/12/2022] [Accepted: 11/19/2022] [Indexed: 11/25/2022]
Abstract
We carried out a systematic review and meta-analysis to investigate the effects of stimulant and non-stimulant medications on autonomic functioning in people with ADHD (PROSPERO: CRD42020212439). We searched (9th August 2021) PsycInfo, MEDLINE, EMBASE, Web of Science and The Cochrane Library, for randomised and non-randomised studies reporting indices of autonomic activity, (electrodermal, pupillometry and cardiac), pre- and post-medication exposure in people meeting DSM/ICD criteria for ADHD. In the narrative syntheses, we included 5 electrodermal studies, 1 pupillometry study and 57 studies investigating heart rate and blood pressure. In the meta-analyses, 29 studies were included on blood pressure and 32 on heart rate. Administration of stimulants, and to a lesser degree, non-stimulants increased heart rate and blood pressure in people with ADHD. Similarly, an upregulation of arousal, reflected in increased electrodermal activity and pupil diameter was observed following stimulant use. Yet, the methodological diversity of studies presented in this review reinforces the need for more standardised and rigorous research to fully understand the relationship between arousal, medication, and behaviour in ADHD.
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Affiliation(s)
- Iman Idrees
- Academic Unit of Mental Health & Clinical Neurosciences, School of Medicine, Institute of Mental Health, University of Nottingham, Nottingham, UK.
| | - Alessio Bellato
- School of Psychology, University of Nottingham Malaysia, Malaysia
| | - Samuele Cortese
- Academic Unit of Mental Health & Clinical Neurosciences, School of Medicine, Institute of Mental Health, University of Nottingham, Nottingham, UK; Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA
| | - Madeleine J Groom
- Academic Unit of Mental Health & Clinical Neurosciences, School of Medicine, Institute of Mental Health, University of Nottingham, Nottingham, UK
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24
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Grünblatt E, Homolak J, Babic Perhoc A, Davor V, Knezovic A, Osmanovic Barilar J, Riederer P, Walitza S, Tackenberg C, Salkovic-Petrisic M. From attention-deficit hyperactivity disorder to sporadic Alzheimer's disease-Wnt/mTOR pathways hypothesis. Front Neurosci 2023; 17:1104985. [PMID: 36875654 PMCID: PMC9978448 DOI: 10.3389/fnins.2023.1104985] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/31/2023] [Indexed: 02/18/2023] Open
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disorder with the majority of patients classified as sporadic AD (sAD), in which etiopathogenesis remains unresolved. Though sAD is argued to be a polygenic disorder, apolipoprotein E (APOE) ε4, was found three decades ago to pose the strongest genetic risk for sAD. Currently, the only clinically approved disease-modifying drugs for AD are aducanumab (Aduhelm) and lecanemab (Leqembi). All other AD treatment options are purely symptomatic with modest benefits. Similarly, attention-deficit hyperactivity disorder (ADHD), is one of the most common neurodevelopmental mental disorders in children and adolescents, acknowledged to persist in adulthood in over 60% of the patients. Moreover, for ADHD whose etiopathogenesis is not completely understood, a large proportion of patients respond well to treatment (first-line psychostimulants, e.g., methylphenidate/MPH), however, no disease-modifying therapy exists. Interestingly, cognitive impairments, executive, and memory deficits seem to be common in ADHD, but also in early stages of mild cognitive impairment (MCI), and dementia, including sAD. Therefore, one of many hypotheses is that ADHD and sAD might have similar origins or that they intercalate with one another, as shown recently that ADHD may be considered a risk factor for sAD. Intriguingly, several overlaps have been shown between the two disorders, e.g., inflammatory activation, oxidative stress, glucose and insulin pathways, wingless-INT/mammalian target of rapamycin (Wnt/mTOR) signaling, and altered lipid metabolism. Indeed, Wnt/mTOR activities were found to be modified by MPH in several ADHD studies. Wnt/mTOR was also found to play a role in sAD and in animal models of the disorder. Moreover, MPH treatment in the MCI phase was shown to be successful for apathy including some improvement in cognition, according to a recent meta-analysis. In several AD animal models, ADHD-like behavioral phenotypes have been observed indicating a possible interconnection between ADHD and AD. In this concept paper, we will discuss the various evidence in human and animal models supporting the hypothesis in which ADHD might increase the risk for sAD, with common involvement of the Wnt/mTOR-pathway leading to lifespan alteration at the neuronal levels.
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Affiliation(s)
- Edna Grünblatt
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich (PUK), University of Zurich, Zurich, Switzerland.,Neuroscience Center Zurich, University of Zurich and the Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.,Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
| | - Jan Homolak
- Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Ana Babic Perhoc
- Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Virag Davor
- Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Ana Knezovic
- Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Jelena Osmanovic Barilar
- Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Peter Riederer
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany.,Department and Research Unit of Psychiatry, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Susanne Walitza
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich (PUK), University of Zurich, Zurich, Switzerland.,Neuroscience Center Zurich, University of Zurich and the Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.,Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
| | - Christian Tackenberg
- Neuroscience Center Zurich, University of Zurich and the Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.,Institute for Regenerative Medicine (IREM), University of Zurich, Schlieren, Switzerland
| | - Melita Salkovic-Petrisic
- Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
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25
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Reciprocal effects of single or repeated exposure to methylphenidate or sex in adult male rats. Psychopharmacology (Berl) 2023; 240:227-237. [PMID: 36544054 DOI: 10.1007/s00213-022-06300-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022]
Abstract
RATIONALE Exposure to rewards can alter behavioral reactivity to them. For example, stimulants sensitize locomotor activation, whereas sexual experience sensitizes copulatory behaviors. Moreover, rewards can cross-sensitize one another. Although stimulants are known to cross-sensitize locomotor effects, the evidence for cross-sensitization between stimulants and sex is less clear. OBJECTIVES This study determined the effects of single and repeated pre-exposure to methylphenidate (MPH) or sex on one another in adult male rats. METHODS Cross-sensitization between MPH (5 mg/kg) and sex (30 min with sexually experienced female) was examined. Adult male rats were pre-exposed to 0, 1, or 10 trials of either sex or MPH before being exposed to the other reward. Locomotor chambers were used in MPH trials. Bilevel chambers were used in sexual trials, and sexual behaviors were video scored. RESULTS The amount of prior sexual experience differentially influenced the ceiling of MPH-dependent sensitization; in the last drug trial, locomotion was highest in males given 1 previous sexual trial compared with 0 or 10. Compared with MPH-naive males, pre-exposure to MPH (1 and 10 trials) reduced the number of ejaculations without impacting sexual performance (intromission/mount latency and frequency). CONCLUSIONS These findings indicate that the degree of pre-exposure to a reward can differentially affect reactivity to novel rewards. The results showed that previous findings of cross-sensitization between amphetamine and sex do not extend to MPH. However, exposure to MPH prior to sexual experience can increase the amount of sexual stimulation needed to achieve ejaculation.
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Breda V, Cerqueira RO, Ceolin G, Koning E, Fabe J, McDonald A, Gomes FA, Brietzke E. Is there a place for dietetic interventions in adult ADHD? Prog Neuropsychopharmacol Biol Psychiatry 2022; 119:110613. [PMID: 35964708 DOI: 10.1016/j.pnpbp.2022.110613] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 07/20/2022] [Accepted: 08/08/2022] [Indexed: 10/15/2022]
Abstract
Current treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in adults are limited by lack of response and side effects in about one third of the individuals. Changes towards a healthier lifestyle could have a positive impact beyond the relief of specific symptoms. However, it is not clear if nutritional interventions influence mental health and cognition. The objective of this study was to summarize the available literature addressing the impact of different diets in ADHD. The most promising dietetic approaches in ADHD are diets considered to be healthy (Mediterranean-type; DASH) and the Few-Foods Diet for children. Studies should take into account the presence of multiple confounders, biases associated with difficulties in blinding participants and researchers, and search for possible mechanisms of action, so we can have better evidence to guide clinical mental care of adults with ADHD.
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Affiliation(s)
- Vitor Breda
- Department of Psychiatry, Queen's University School of Medicine, 752 King Street West, Kingston, ON K7L 7X3, Canada; Centre for Neuroscience Studies (CNS), Queen's University, 18 Stuart Street, Kingston, ON K7L 3N6, Canada.
| | - Raphael O Cerqueira
- Department of Psychiatry, Federal University of São Paulo, Rua Major Maragliano 241, São Paulo, SP 04017-030, Brazil
| | - Gilciane Ceolin
- Postgraduate Program in Nutrition, Federal University of Santa Catarina, Rua Delfino Conti, Campus Trindade, Florianópolis, SC 88040-970, Brazil
| | - Elena Koning
- Department of Psychiatry, Queen's University School of Medicine, 752 King Street West, Kingston, ON K7L 7X3, Canada; Centre for Neuroscience Studies (CNS), Queen's University, 18 Stuart Street, Kingston, ON K7L 3N6, Canada.
| | - Jennifer Fabe
- McMasters Children's Hospital, Hamilton Health Sciences, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada.
| | | | - Fabiano A Gomes
- Department of Psychiatry, Queen's University School of Medicine, 752 King Street West, Kingston, ON K7L 7X3, Canada; Centre for Neuroscience Studies (CNS), Queen's University, 18 Stuart Street, Kingston, ON K7L 3N6, Canada.
| | - Elisa Brietzke
- Department of Psychiatry, Queen's University School of Medicine, 752 King Street West, Kingston, ON K7L 7X3, Canada; Centre for Neuroscience Studies (CNS), Queen's University, 18 Stuart Street, Kingston, ON K7L 3N6, Canada.
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27
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Gilmore D, Longo A, Krantz M, Radford D, Hand BN. Five Ways Providers Can Improve Mental Healthcare for Autistic Adults: A Review of Mental Healthcare Use, Barriers to Care, and Evidence-Based Recommendations. Curr Psychiatry Rep 2022; 24:565-571. [PMID: 35969335 PMCID: PMC9376572 DOI: 10.1007/s11920-022-01362-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/21/2022] [Indexed: 01/29/2023]
Abstract
PURPOSE OF REVIEW We reviewed the literature from 2017 to 2022 on autistic adults' use of mental healthcare and barriers to care. To encourage immediate improvement in mental healthcare, we provide five strategies mental health providers can use to better care for autistic adults. RECENT FINDINGS Most autistic adults use mental healthcare and use it more often than non-autistic adults. Autistic adults' experiences with mental healthcare are characterized by (1) lack of providers knowledgeable about autism, (2) use of treatments that may not be accommodating to individual needs, and (3) difficulty navigating the complex healthcare system. These barriers contribute to prevalent unmet needs for mental healthcare. Autistic adults use mental healthcare frequently but have unmet mental health needs. As necessary systemic changes develop, providers can begin immediately to better care for autistic adults by learning about their needs and taking personalized care approaches to meet those needs.
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Affiliation(s)
- Daniel Gilmore
- The Ohio State University, 228E Atwell Hall, 453 W 10th Ave., Columbus, OH 43210 USA
| | - Anne Longo
- The Ohio State University, 228E Atwell Hall, 453 W 10th Ave., Columbus, OH 43210 USA
| | - Morgan Krantz
- The Ohio State University, 228E Atwell Hall, 453 W 10th Ave., Columbus, OH 43210 USA
| | - Deondray Radford
- The Ohio State University, 228E Atwell Hall, 453 W 10th Ave., Columbus, OH 43210 USA
| | - Brittany N. Hand
- The Ohio State University, 228E Atwell Hall, 453 W 10th Ave., Columbus, OH 43210 USA
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Dutta CN, Christov-Moore L, Ombao H, Douglas PK. Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan. Front Hum Neurosci 2022; 16:938501. [PMID: 36226261 PMCID: PMC9548548 DOI: 10.3389/fnhum.2022.938501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/16/2022] [Indexed: 11/13/2022] Open
Abstract
For decades, psychostimulants have been the gold standard pharmaceutical treatment for attention-deficit/hyperactivity disorder (ADHD). In the United States, an astounding 9% of all boys and 4% of girls will be prescribed stimulant drugs at some point during their childhood. Recent meta-analyses have revealed that individuals with ADHD have reduced brain volume loss later in life (>60 y.o.) compared to the normal aging brain, which suggests that either ADHD or its treatment may be neuroprotective. Crucially, these neuroprotective effects were significant in brain regions (e.g., hippocampus, amygdala) where severe volume loss is linked to cognitive impairment and Alzheimer's disease. Historically, the ADHD diagnosis and its pharmacotherapy came about nearly simultaneously, making it difficult to evaluate their effects in isolation. Certain evidence suggests that psychostimulants may normalize structural brain changes typically observed in the ADHD brain. If ADHD itself is neuroprotective, perhaps exercising the brain, then psychostimulants may not be recommended across the lifespan. Alternatively, if stimulant drugs are neuroprotective, then this class of medications may warrant further investigation for their therapeutic effects. Here, we take a bottom-up holistic approach to review the psychopharmacology of ADHD in the context of recent models of attention. We suggest that future studies are greatly needed to better appreciate the interactions amongst an ADHD diagnosis, stimulant treatment across the lifespan, and structure-function alterations in the aging brain.
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Affiliation(s)
- Cintya Nirvana Dutta
- Biostatistics Group, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
- School of Modeling, Simulation, and Training, and Computer Science, University of Central Florida, Orlando, FL, United States
| | - Leonardo Christov-Moore
- Brain and Creativity Institute, University of Southern California, Los Angeles, CA, United States
| | - Hernando Ombao
- Biostatistics Group, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
| | - Pamela K. Douglas
- School of Modeling, Simulation, and Training, and Computer Science, University of Central Florida, Orlando, FL, United States
- Department of Psychiatry and Biobehavioral Medicine, University of California, Los Angeles, Los Angeles, CA, United States
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Childress A, Burton S. Evaluating the pharmacokinetics of extended release viloxazine in the treatment of children with attention-deficit/hyperactivity disorder. Expert Opin Drug Metab Toxicol 2022; 18:357-366. [PMID: 35848085 DOI: 10.1080/17425255.2022.2103406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood and impacts function negatively in multiple settings. Current treatments include stimulants, which inhibit the reuptake of dopamine and norepinephrine, a nonstimulant norepinephrine reuptake inhibitor (NRI) atomoxetine, and alpha-2 agonists clonidine extended release (ER) and guanfacine ER. Despite the effectiveness of these medications some patients do not respond to available drugs or may experience tolerability issues that hinder their use. AREAS COVERED Viloxazine, a serotonin norepinephrine modulating agent, was used outside of the United States (U.S.) as an effective antidepressant for several decades, but its use fell out of favor due to the need for multiple daily dosing. An ER viloxazine formulation was recently approved by the U. S. Food and Drug Administration (FDA) for the treatment of ADHD. The efficacy, pharmacokinetics and metabolism of viloxazine and viloxazine ER are reviewed. EXPERT OPINION Viloxazine ER is the first nonstimulant approved to treat ADHD in more than a decade. Although they have not been directly compared, the effect size of viloxazine ER is less than has been observed for stimulants. However, its pharmacokinetic properties and tolerability make viloxazine ER a useful addition to the collection of FDA approved ADHD treatments.
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Affiliation(s)
- Ann Childress
- Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, Nevada, USA
| | - Shelby Burton
- Touro University, Nevada College of Osteopathic Medicine, Nevada, USA
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Pharmacotherapy of Attention-Deficit/Hyperactivity Disorder in Individuals with Autism Spectrum Disorder. Child Adolesc Psychiatr Clin N Am 2022; 31:449-468. [PMID: 35697395 DOI: 10.1016/j.chc.2022.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is the most frequent comorbid disorder that is observed at a higher rate and with greater morbidity in higher intellectually functioning populations with autism. Up to 85% of the populations with autism and 15% of individuals with ADHD suffer from a reciprocal comorbidity that is highly under-recognized in intellectually capable populations. Limited empirical evidence is available on the response of anti-ADHD agents in autism populations with ADHD. In autism spectrum disorder (ASD) populations, response to methylphenidate for the treatment of hyperactivity is worse than typically expected in the presence of the intellectual disability. The anti-ADHD response to atomoxetine in autism populations is worse than typically expected although tolerability is similar to that observed in the typicals. The hyperactivity response to guanfacine treatment in predominantly intellectually impaired populations with ASD is as robust as observed in the typicals although tolerability was worse than typically expected. Further trials are warranted to document the extent of atypical anti-ADHD response in intellectually capable populations with autism.
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Abstract
Stimulants have been available for the treatment of attention-deficit/hyperactivity disorder (ADHD) for more than 70 years and are the most effective medications available. During the past 2 decades, several new immediate-release (IR) and extended-release methylphenidate (MPH) and amphetamine (AMPH) formulations have become available. These products differ by dose form (capsules, tablets, oral suspensions, oral disintegrating tablets, and patch), by onset and duration of effect, and by bioavailability. The side effect profile is generally similar for all compounds. Although the products are similar, individual patients may have a better response or tolerability to a particular class (MPH or AMPH) or formulation.
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Affiliation(s)
- Ann C Childress
- Center for Psychiatry and Behavioral Medicine, Inc., 7351 Prairie Falcon Road, Suite 160, Las Vegas, NV 89128, USA.
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Nermend M, Flaga-Gieruszyńska K, Kroplewski Z, Nermend K. Neurological Mechanisms of Diagnosis and Therapy in School Children with ADHD in Poland. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19137615. [PMID: 35805275 PMCID: PMC9265331 DOI: 10.3390/ijerph19137615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/15/2022] [Accepted: 06/21/2022] [Indexed: 11/24/2022]
Abstract
The paper aims to present a holistic view of attention deficit hyperactivity disorder (ADHD) in pedagogical, psychological, legal, and social dimensions in Polish schools. The authors present the benefits of neurofeedback therapy for elementary school pupils. In order to verify the validity, the paper compares the concordance of a medical diagnosis confirming ADHD syndrome with the occurrence of abnormal electrical brain function recording and abnormalities therein as well as the effectiveness of the neurofeedback therapy. The study confirms that the reported problems faced by pupils and affecting their emotional functioning are reflected in their EEG records. Conclusions from the study lead to the proposal that the neurofeedback assessment should be performed at schools, which should result in the implementation of effective therapy. Moreover, the neurofeedback method should be promoted in Polish schools as an alternative to pharmacological therapy, which, as the research proves, is not always effective. Neurofeedback therapy, similarly to behavioral therapy, is very much needed and useful because it provides optimal conditions for the child’s development and shapes their relations with the environment effectively and harmlessly.
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Affiliation(s)
- Małgorzata Nermend
- Department of Early Education, University of Szczecin, 71-004 Szczecin, Poland;
| | - Kinga Flaga-Gieruszyńska
- Research Team on Civil Procedural Law and Informatization of the Justice, Faculty of Law and Administration, University of Szczecin, 71-101 Szczecin, Poland;
| | - Zdzisław Kroplewski
- Institute of Psychology, University of Szczecin, Krakowska 69, 71-017 Szczecin, Poland;
| | - Kesra Nermend
- Department of Decision Support Methods and Cognitive Neuroscience, Institute of Management, University of Szczecin, 71-004 Szczecin, Poland
- Correspondence:
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Vertessen K, Luman M, Staff A, Bet P, de Vries R, Twisk J, Oosterlaan J. Meta-analysis: Dose-Dependent Effects of Methylphenidate on Neurocognitive Functioning in Children With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry 2022; 61:626-646. [PMID: 34534624 DOI: 10.1016/j.jaac.2021.08.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 08/09/2021] [Accepted: 09/07/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Neurocognitive deficits are at the heart of explanatory models of attention-deficit/hyperactivity disorder (ADHD), and lead to significant impairments in daily life. Determining the dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigating possible impairing effects of high doses is therefore important. METHOD Placebo-controlled trials were included that investigated MPH dosing effects on neurocognitive functions in children and adolescents (aged 5-18 years) diagnosed with ADHD. Effect sizes (standardized mean differences [SMDs]) were calculated for different neurocognitive functions (baseline speed, variability in responding, nonexecutive memory and executive memory, inhibitory control, and cognitive flexibility) and, if available, for ADHD symptoms. Meta-regression analysis were used to investigate linear effects of dose (mg/kg/dose), and separate meta-analyses compared SMDs for 3 MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose), and high (0.61-1.00 mg/kg/dose). RESULTS A total of 31 studies fulfilled inclusion criteria, comprising 804 children with ADHD. Methylphenidate had beneficial effects on all neurocognitive functions (d = 0.20-0.73). Significant linear dosing effects were found for ADHD symptoms and lower-order neurocognitive functions (baseline speed, variability in responding, nonexecutive memory), with greater enhancement of functioning with increasing dose. No dosing effects were found for higher-order neurocognitive functions (executive memory, inhibitory control, and cognitive flexibility). No detrimental effects of MPH were found on any of the investigated functions. CONCLUSION Methylphenidate was superior to placebo in improving ADHD symptoms and a broad range of neurocognitive functions; however, effects sizes regarding the effects of dose vary substantially between functions. Our data highlight the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice.
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Affiliation(s)
- Karen Vertessen
- VU Amsterdam, the Netherlands; University Psychiatric Centre, Katholieke Universiteit Leuven, Belgium.
| | | | | | - Pierre Bet
- Amsterdam UMC, VU Medical Center, Amsterdam, the Netherlands
| | | | - Jos Twisk
- Amsterdam UMC, VU Medical Center, Amsterdam, the Netherlands
| | - Jaap Oosterlaan
- VU Amsterdam, the Netherlands; Amsterdam UMC, VU Medical Center, Amsterdam, the Netherlands
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Lilja MM, Sandblom E, Lichtenstein P, Serlachius E, Hellner C, Bhagia J, Halldner L. The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort. J Neurodev Disord 2022; 14:17. [PMID: 35249540 PMCID: PMC8903657 DOI: 10.1186/s11689-022-09424-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/14/2022] [Indexed: 12/27/2022] Open
Abstract
Background Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms. Methods In a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up. Results From baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group. Conclusions Our results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD. Trial registration NCT02136147, May 12, 2014.
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35
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Keng A, Stewart DE, Sheehan KA. Neuropsychiatric Symptoms After Brain Tumor Resection in Children and Adolescents: A Scoping Review. J Acad Consult Liaison Psychiatry 2022; 63:110-118. [PMID: 34229094 DOI: 10.1016/j.jaclp.2021.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 06/23/2021] [Accepted: 06/26/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND Brain tumors are one of the most common solid tumors in pediatric populations, with their treatments having significant neuropsychiatric impact. OBJECTIVE The objective of this study was to review the literature on neuropsychiatric sequelae after surgical resection of brain tumors in children and adolescents. METHODS Using a scoping method, we reviewed empirical articles describing pediatric patients with brain tumors who underwent partial or total resection and examined major neuropsychiatric domains postoperatively over time. RESULTS The initial search yielded 15,543 articles. After duplicate removal, abstract screening, and review, 44 articles were included. Cognitive deficits were the most widely studied outcomes and found to be associated with tumor location, operative variables, perioperative complications, treatment types, and psychosocial factors. Cerebellar mutism, or posterior fossa syndrome, commonly co-occurred with emotional and behavioral dysregulation after posterior fossa resections. Depression, anxiety, and somatization were frequently grouped together as "distress," with higher rates among pediatric patients with brain tumor than among healthy peers. Problematic school behaviors, antisocial, and attention-deficit traits were increased; however, several other behaviors (e.g., risky sexual behaviors, substance use) were equal or lower when compared to peers. Posttraumatic stress disorder was highly prevalent and often interfered with social functioning. Delirium, eating disorders, and longer-term outcomes received inadequate attention. CONCLUSION Identifying risk factors of neuropsychiatric sequelae and their impact after pediatric brain tumor resection is important for prognostication and the development of tailored management strategies for these children and adolescents.
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Affiliation(s)
- Alvin Keng
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
| | - Donna E Stewart
- Centre for Mental Health, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Kathleen Ann Sheehan
- Centre for Mental Health, University Health Network, University of Toronto, Toronto, ON, Canada
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Rahmani E, Mahvelati A, Alizadeh A, Mokhayeri Y, Rahmani M, Zarabi H, Hassanvandi S. Is neurofeedback effective in children with ADHD? A systematic review and meta-analysis. Neurocase 2022; 28:84-95. [PMID: 35068368 DOI: 10.1080/13554794.2022.2027456] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
To evaluate the evidences related to the effectiveness of neurofeedback treatment for children and adolescent with attention-deficit/hyperactivity disorder (ADHD) based on the most-proximal raters. A systematic review of randomized control trials (RCTs) was carried out across multiple databases. the primary outcome measure was the most proximal ratings of ADHD symptoms in subjects. Conner's Parent Rating Scale (CPRS), Conner's Teacher Rating Scale (CTRS), and ADHD Rating Scale (ADHD-RS- are considered as primary outcomes. Seventeen trials met inclusion criteria (including 1211 patients). Analysis showed that there was no significant benefit of neurofeedback treatment compared with other treatments or control conditions [weighted mean difference/CI = HI-P: -0.02 (-0.26, 0.21), HI-T: 0.01 (-0.46, 0.48), weighted mean difference/CI = I-P: 0.00 (-0.23, 0.23), I-P: 0.12 (-0.14, 0.38)]. The results provide preliminary evidence that neurofeedback treatment is no efficacious clinical method for ADHD and suggest that more RTCs are needed to compare common treatment .
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Affiliation(s)
- Ebrahim Rahmani
- Counseling Psychology, Razi University of Kermanshah, Kermanshah, Iran
| | - Azadeh Mahvelati
- Department of counseling, Imam Reza International University, Mashhad, Iran
| | - Aida Alizadeh
- Department of Clinical Psychology, Faculty of Education and Psychology, University of Science and Research Branch, Tehran, Iran
| | - Yaser Mokhayeri
- Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Masoud Rahmani
- Clinical Psychology, Department of Human and Social Sciences, University of Bergamo, Bergamo, Italy
| | - Hamid Zarabi
- Department of Clinical Psychology, School of Behavior Science and Mental Health (Tehran Institute of Psychiatry), Iran University of Medical Science, Tehran, Iran
| | - Saba Hassanvandi
- Department of Psychology, Faculty of Humanistic Sciences, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
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Moderators and Other Predictors of Methylphenidate Response in Children and Adolescents with ADHD. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19031640. [PMID: 35162663 PMCID: PMC8834961 DOI: 10.3390/ijerph19031640] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/25/2022] [Accepted: 01/28/2022] [Indexed: 11/23/2022]
Abstract
Methylphenidate (MPH) is the treatment of first choice for developmental ADHD. To date, no reliable method to predict how patients will respond to MPH exists and conflicting results are reported on clinical characteristics of responders. The present study aims to give a more precise characterization of the patients who will respond best to MPH to help clinicians in defining the treatment plan. Age, neuropsychological functioning (i.e., attention and working memory), and behavioral/emotional symptoms of 48 drug-naïve children and adolescents with ADHD (42 boys and 6 girls, age-range 6–16 years, mean age 10.5 ± 2.5 years, mean IQ 101.3 ± 11.2) were studied to assess how these different characteristics affected a single-dose MPH response. Four hierarchical linear regression models were used to explore whether age, neuropsychological measures at baseline, and behavioral/emotional symptoms could predict attention and working memory measures after a single-dose MPH administration. We found that improvement in attention and working memory was predicted by age, neuropsychological measures at baseline, and severity of ADHD symptoms. No behavioral and emotional symptoms predicted single-dose MPH response with the exception of conduct symptoms.
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Heal DJ, Gosden J, Smith SL. New Drugs to Treat ADHD: Opportunities and Challenges in Research and Development. Curr Top Behav Neurosci 2022; 57:79-126. [PMID: 35507283 DOI: 10.1007/7854_2022_332] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Since the landmark MTA (Multimodal Treatment of ADHD) trial unequivocally demonstrated the efficacy of methylphenidate, catecholaminergic drugs, especially stimulants, have been the therapeutic mainstay in treatment of Attention-Deficit Hyperactivity Disorder (ADHD). We review the new drugs which have entered the ADHD formulary. The lessons learned from drug-candidates that have succeeded in clinical trials together with those that have not have also been considered. What emerges confirms and consolidates the hypothesis that clinically effective ADHD drugs indirectly or directly increase catecholaminergic neurotransmission in the prefrontal cortex (PFC). Attempts to enhance catecholaminergic signalling through modulatory neurotransmitter systems or cognitive-enhancing drugs have all failed. New drugs approved for ADHD are catecholaminergic reuptake inhibitors and releasing agents, or selective noradrenaline reuptake inhibitors. Triple reuptake inhibitors with preferential effects on dopamine have not been successful. The substantial number of failures probably accounts for a continued focus on developing novel catecholaminergic and noradrenergic drugs, and a dearth of drug-candidates with novel mechanisms entering clinical development. However, substantial improvements in ADHD pharmacotherapy have been achieved by the almost exclusive use of once-daily medications and prodrugs, e.g. lisdexamfetamine and Azstarys®, which improve compliance, deliver greater efficacy and reduce risks for diversion and abuse.
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Affiliation(s)
- David J Heal
- DevelRx Ltd, Nottingham, UK.
- Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
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Abstract
Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition associated with impaired function and increased risk of poor outcomes in children, young people and adults with the condition. Currently approved pharmacological treatments for ADHD include a range of stimulant (methylphenidate, amphetamine) and nonstimulant (atomoxetine, guanfacine, clonidine) medications. All have been shown to be effective in treating the symptoms of ADHD and improving other functional outcomes including quality of life, academic performance, rates of accidents and injuries, and do not appear to be associated with significant adverse outcomes or side effects. In this chapter, we review medications for ADHD by summarising the mechanisms of action of each of the two main classes of compounds (stimulants and nonstimulants), the formulations of the most commonly prescribed medications within each class, their efficacy in treating ADHD symptoms and other outcomes, and other factors that influence treatment decisions including side effects and tolerability, comorbidities and medical history. We conclude with a summary of the treatment decisions made by clinicians and suggest some next steps for research. Further research is needed to understand the mechanisms of action of these medications and how exactly they improve symptoms, and to examine their effects on commonly occurring comorbidities.
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Affiliation(s)
- Madeleine J Groom
- Academic Unit of Mental Health and Clinical Neurosciences, School of Medicine, Institute of Mental Health, University of Nottingham, Nottingham, UK.
| | - Samuele Cortese
- Faculty of Environmental and Life Sciences, Center for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
- Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK
- Solent NHS Trust, Southampton, UK
- Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA
- Centre for ADHD and Neurodevelopmental Disorders Across the Lifespan, Institute of Mental Health, University of Nottingham, Nottingham, UK
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Biederman J, DiSalvo M, Green A, Woodworth KY, Gilfix T, Law C, Gabrieli J, Faraone SV. Rates of switching stimulants in consecutively referred medication naïve adults with ADHD. Acta Psychiatr Scand 2021; 144:626-634. [PMID: 34537970 DOI: 10.1111/acps.13370] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/25/2021] [Accepted: 08/28/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To evaluate the frequency and correlates of needing to switch the initial treatment with a stimulant medication to the alternative family in newly referred, untreated adults with ADHD initiating treatment. METHODS Subjects were consecutively referred unmedicated adults with DSM-5 ADHD who initiated stimulant treatment. Before assessment with an expert clinician, participants completed a battery of self-report measures to assess psychopathology, executive functioning, emotional dysregulation, and mind wandering. The rate of switching was examined using information from electronic medical records for up to three clinical follow-up visits. Those who did and did not need to switch were compared on baseline demographic and clinical characteristics. RESULTS Twenty-four percent (N = 21/86) of ADHD patients needed to switch from their initially prescribed stimulant family within 60 days of initiating treatment due to poor tolerability. While the rate of switching was significantly higher in those initially prescribed MPH, the rate of patients requiring changes in formulation or additional antianxiety or antidepressant treatment was higher in those taking AMPH. There were some hints about predictive risk factors for switching by the presence of emotional dysregulation and depressive symptoms, depending on age and sex. CONCLUSIONS These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying safe and effective treatments for these patients.
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Affiliation(s)
- Joseph Biederman
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.,Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
| | - Maura DiSalvo
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Allison Green
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - K Yvonne Woodworth
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Talia Gilfix
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Cecilia Law
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - John Gabrieli
- MIT Integrated Learning Initiative, Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Stephen V Faraone
- Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Boston, Massachusetts, USA.,Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, USA
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Brikell I, Burton C, Mota NR, Martin J. Insights into attention-deficit/hyperactivity disorder from recent genetic studies. Psychol Med 2021; 51:2274-2286. [PMID: 33814023 DOI: 10.1017/s0033291721000982] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder (NDD). In this narrative review, we summarize recent advances in quantitative and molecular genetic research from the past 5-10 years. Combined with large-scale international collaboration, these advances have resulted in fast-paced progress in understanding the etiology of ADHD and how genetic risk factors map on to clinical heterogeneity. Studies are converging on a number of key insights. First, ADHD is a highly polygenic NDD with a complex genetic architecture encompassing risk variants across the spectrum of allelic frequencies, which are implicated in neurobiological processes. Second, genetic studies strongly suggest that ADHD diagnosis shares a large proportion of genetic risks with continuously distributed traits of ADHD in the population, with shared genetic risks also seen across development and sex. Third, ADHD genetic risks are shared with those implicated in many other neurodevelopmental, psychiatric and somatic phenotypes. As sample sizes and the diversity of genetic studies continue to increase through international collaborative efforts, we anticipate further success with gene discovery, characterization of how the ADHD phenotype relates to other human traits and growing potential to use genomic risk factors for understanding clinical trajectories and for precision medicine approaches.
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Affiliation(s)
- Isabell Brikell
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- National Centre for Register-based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark
| | - Christie Burton
- Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Canada
| | - Nina Roth Mota
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
| | - Joanna Martin
- MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
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Maeder J, Mancini V, Sandini C, Journal F, Schneider M, Kliegel M, Eliez S. Selective Effects of Methylphenidate on Attention and Inhibition in 22q11.2 Deletion Syndrome: Results From a Clinical Trial. Int J Neuropsychopharmacol 2021; 25:215-225. [PMID: 34453525 PMCID: PMC8929751 DOI: 10.1093/ijnp/pyab057] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 08/13/2021] [Accepted: 08/20/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Attention deficit and/or hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children with 22q11.2 deletion syndrome (22q11DS) and frequently persists into adulthood. Although medication with stimulant has been demonstrated to be highly effective in idiopathic ADHD, evidence in 22q11DS is still scarce. Previous studies have shown safety and effectiveness of methylphenidate (MPH) on core symptoms of ADHD as well as improvement of associated cognitive deficits. However, only a limited number of cognitive domains have been explored. METHODS Twenty-three participants with 22q11DS and attention difficulties, aged 8-24 years, entered a clinical trial aiming to specify the effects of MPH on clinical symptoms, cognition, and daily-life behavior. The effects of treatment were compared with/without medication in a within-subject design. The trial included both participants naïve to the molecule and chronic users. RESULTS Benefit from the treatment was demonstrated through a decrease in core ADHD symptoms, specifically inattention symptoms, and improvement of cognitive measures of attention and inhibition. Conversely, no significant change was found for other executive functions (such as cognitive flexibility, working memory, initiation), learning, or memory. Moreover, no significant improvement on ecological measures of daily-life executive functioning was found, possibly because of the short treatment period. We replicated safety, and although very frequent, side effects were of mild intensity and comparable with previous findings. CONCLUSIONS This study extends the current knowledge on the effects of MPH in patients with 22q11DS. Treatment was found to be effective for core ADHD symptoms and cognitive measures of attention and inhibition.
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Affiliation(s)
- Johanna Maeder
- Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland,Correspondence: Johanna Maeder, PhD, Developmental Imaging and Psychopathology Laboratory, Campus Biotech, Chemin des Mines 9, 1202 Geneva, Switzerland ()
| | - Valentina Mancini
- Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland
| | - Corrado Sandini
- Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland
| | - Fiona Journal
- Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland
| | - Maude Schneider
- Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland,Clinical Psychology Unit for Intellectual and Developmental Disabilities, Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland,Center for Contextual Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium
| | - Matthias Kliegel
- Cognitive Aging Laboratory, Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland,Center for the Interdisciplinary Study of Gerontology and Vulnerability, and Swiss National Center of Competences in Research LIVES–Overcoming Vulnerability: Life Course Perspectives, Geneva, Switzerland
| | - Stephan Eliez
- Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland,Department of Genetic Medicine and Development, University of Geneva, Switzerland
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Nasser A, Kosheleff AR, Hull JT, Liranso T, Qin P, Busse GD, Fava M, Maletic V, Rubin J, Lopez F. Evaluating the likelihood to be helped or harmed after treatment with viloxazine extended-release in children and adolescents with attention-deficit/hyperactivity disorder. Int J Clin Pract 2021; 75:e14330. [PMID: 33971070 PMCID: PMC8365735 DOI: 10.1111/ijcp.14330] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 04/16/2021] [Accepted: 05/03/2021] [Indexed: 12/20/2022] Open
Abstract
AIMS When clinicians evaluate potential medications for their patients, they must weigh the probability of a treatment's benefits against the possible risks. To this end, the present analyses evaluate the novel nonstimulant viloxazine extended-release (viloxazine ER) using measures of effect size to describe the potential benefits of its treatment in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) as well as the risk of discontinuation because of intolerable adverse events. METHODS These post hoc analyses use pooled data from four pivotal Phase 3 trials in paediatric patients treated with viloxazine ER. The Likelihood to be Helped or Harmed (LHH) effect size measure was calculated to describe the probability of patients benefiting from treatment vs discontinuing. The Number Needed to Treat (NNT) was calculated from frequently used thresholds of response. The Number Needed to Harm (NNH) was calculated using discontinuations because of adverse events. RESULTS LHH values for viloxazine ER ranged from 5 to 13, suggesting that subjects were 5-13 times more likely to benefit from, rather than discontinue, viloxazine ER treatment. Specifically, NNT values for viloxazine ER treatment ranged from 6 to 7. NNH values for viloxazine ER treatment ranged from 31 to 74. By convention, single-digit NNTs (<10) suggest the intervention is potentially useful, while NNH values ≥10 for adverse events suggest it is potentially safe or tolerable. CONCLUSIONS These results indicate that patients with ADHD are likely to benefit from treatment with viloxazine ER, and are unlikely to discontinue, as viloxazine ER treatment was associated with favourable LHH, NNT, and NNH values. Clinicaltrials.gov: NCT03247530, NCT03247543, NCT03247517, NCT03247556.
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Affiliation(s)
- Azmi Nasser
- Supernus Pharmaceuticals, Inc.RockvilleMDUSA
| | | | | | | | - Peibing Qin
- Supernus Pharmaceuticals, Inc.RockvilleMDUSA
| | | | - Maurizio Fava
- Department of PsychiatryMassachusetts General HospitalBostonMAUSA
| | - Vladimir Maletic
- Department of Psychiatry/Behavioral ScienceUniversity of South Carolina School of MedicineGreenvilleSCUSA
| | | | - Frank Lopez
- Children’s Developmental CenterWinter ParkFLUSA
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Fosco WD, Rosch KS, Waxmonsky JG, Pelham WE, Hawk LW. Baseline performance moderates stimulant effects on cognition in youth with ADHD. Exp Clin Psychopharmacol 2021; 29:302-307. [PMID: 32297786 PMCID: PMC8388131 DOI: 10.1037/pha0000374] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Attention-deficit/hyperactivity disorder is associated with impaired cognitive functioning and increased delay discounting (i.e., a stronger preference for immediate reward). At the group level, stimulant medication improves cognition and delay discounting, yet not all children exhibit problems in these domains, and previous work has not examined whether stimulant-induced improvements are moderated by baseline performance. To address this question in the current study, 82 children with attention-deficit/hyperactivity disorder (9-12 years old) attended a week-long research camp. On the baseline day (Monday), participants completed tasks of inhibitory control, visuospatial working memory, reaction time variability, and delay discounting. Children then completed a 3-day, randomized, double-blind, placebo-controlled trial of ∼1 mg/kg and 2 mg/kg long-acting methylphenidate (mean doses = 39.1 and 74.3 mg, respectively), during which they were readministered the battery of tasks. Cognitive composites (mean of inhibitory control, working memory, and reaction time variability performance) were created for the baseline and medication evaluation phases. As predicted, the extent to which cognition was improved with medication compared with placebo and with 2 mg/kg compared with 1 mg/kg was greatest among children with poorer baseline cognitive function. Children with stronger baseline cognition exhibited less improvement with methylphenidate compared with placebo and did not benefit from the 2 compared with the 1 mg/kg dose. In contrast, medication-related improvement in delay discounting was unrelated to baseline discounting. Given that improving cognitive function is one potential mechanisms by which stimulants exert their therapeutic effects, this study has significant implications for understanding how and for whom stimulant medication works. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Affiliation(s)
- Whitney D Fosco
- Center for Children and Families, Florida International University
| | - Keri S Rosch
- Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Johns Hopkins University School of Medicine
| | - James G Waxmonsky
- Department of Psychiatry, Pennsylvania State University College of Medicine
| | - William E Pelham
- Center for Children and Families and Department of Psychology, Florida International University
| | - Larry W Hawk
- Department of Psychology, University at Buffalo, State University of New York
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Mechler K, Banaschewski T, Hohmann S, Häge A. Evidence-based pharmacological treatment options for ADHD in children and adolescents. Pharmacol Ther 2021; 230:107940. [PMID: 34174276 DOI: 10.1016/j.pharmthera.2021.107940] [Citation(s) in RCA: 94] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 05/06/2021] [Indexed: 12/15/2022]
Abstract
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity, causing functional impairment. Its prevalence lies at approximately 5% in children and adolescents and at approximately 2.5% in adults. The disorder follows a multifactorial etiology and shows a high heritability. Patients show a high interindividual and intraindividual variability of symptoms, with executive deficits in several cognitive domains. Overall, ADHD is associated with high rates of psychiatric comorbidities, and insufficient treatment is linked to adverse long-term outcomes. Current clinical guidelines recommend an individualized multimodal treatment approach including psychoeducation, pharmacological interventions, and non-pharmacological interventions. Available medications include stimulants (methylphenidate, amphetamines) and non-stimulants (atomoxetine, guanfacine, clonidine). While available pharmacological treatment options for ADHD show relatively large effect sizes (in short-term trials) and overall good tolerability, there is still a need for improvement of current pharmacotherapeutic strategies and for the development of novel medications. This review summarizes available pharmacological treatment options for ADHD in children and adolescents, identifies current issues in research and evidence gaps, and provides an overview of ongoing efforts to develop new medications for the treatment of ADHD in children and adolescents by means of a systematic cross-sectional analysis of the clinical trials registry www.clinicaltrials.gov.
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Affiliation(s)
- Konstantin Mechler
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
| | - Tobias Banaschewski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Sarah Hohmann
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Alexander Häge
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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Neurofeedback and Attention-Deficit/Hyperactivity-Disorder (ADHD) in Children: Rating the Evidence and Proposed Guidelines. Appl Psychophysiol Biofeedback 2021; 45:39-48. [PMID: 32206963 PMCID: PMC7250955 DOI: 10.1007/s10484-020-09455-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Stimulant medication and behaviour therapy are the most often applied and accepted treatments for Attention-Deficit/Hyperactivity-Disorder (ADHD). Here we explore where the non-pharmacological clinical intervention known as neurofeedback (NFB), fits on the continuum of empirically supported treatments, using standard protocols. In this quantitative review we utilized an updated and stricter version of the APA guidelines for rating ‘well-established’ treatments and focused on efficacy and effectiveness using effect-sizes (ES) and remission, with a focus on long-term effects. Efficacy and effectiveness are compared to medication and behaviour therapy using benchmark studies. Only recent systematic reviews and meta-analyses as well as multi-centre randomized controlled trials (RCT’s) will be included. Two meta-analyses confirmed significant efficacy of standard neurofeedback protocols for parent and teacher rated symptoms with a medium effect size, and sustained effects after 6–12 months. Four multicenter RCT’s demonstrated significant superiority to semi-active control groups, with medium-large effect sizes end of treatment or follow-up and remission rates of 32–47%. Effectiveness in open-label studies was confirmed, no signs of publication bias were found and no significant neurofeedback-specific side effects have been reported. Standard neurofeedback protocols in the treatment of ADHD can be concluded to be a well-established treatment with medium to large effect sizes and 32–47% remission rates and sustained effects as assessed after 6–12 months.
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Yang KH, Lane HY, Chang YC, Tzang RF. Exploring the Effects of Pharmacological, Psychosocial, and Alternative/Complementary Interventions in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Meta-Regression Approach. Int J Neuropsychopharmacol 2021; 24:776-786. [PMID: 34086891 PMCID: PMC8538900 DOI: 10.1093/ijnp/pyab034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 05/23/2021] [Accepted: 06/03/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND There have been various therapies for attention-deficit/hyperactivity disorder (ADHD), but the previous meta-analysis of ADHD efficacy remains unclear. This study aims to systemically meta-regress the effect sizes (ES) of psychostimulant pharmacotherapy (methylphenidate and lisdexamfetamine), non-stimulant pharmacotherapy (atomoxetine and alpha-2 agonists), psychosocial therapy (parental behavioral therapy [PBT]), combination therapy (psychostimulant plus PBT), and alternative/complementary interventions to determine the right treatment for ADHD. METHODS We searched various ADHD interventions from the MEDLINE and PubMed databases (National Center for Biotechnology Information) between January 1, 1980, and July 30, 2018. Following the meta-analysis of random effects, the meta-regression analyses were used to explore factors potentially influencing treatment efficacy. The confounding variables included type of treatment, type of study, age, type of symptom scale used, and year of publication. RESULTS A total of 107 trials (n = 9883 participants) were included. After adjustment, compared with the psychostimulant therapy (28 trial, 2134 participants), non-stimulant pharmacotherapy (28 trials, 4991 participants) and alternative/complement intervention (25 trials, 1195 participants) were less effective by the ES of -0.384 (P = .004) and -0.419 (P = .028), respectively. However, compared with psychostimulant, PBT (19 trials, 1122 participants; ES = -0.308, P = .095) and the combination of psychostimulant and PBT (7 trials, 441participants; ES = -0.196, P = .209) did not differ significantly. CONCLUSIONS Psychostimulant therapy surpassed non-stimulant pharmacotherapy and alternative/complement intervention. Psychostimulant therapy, PBT, and the combination of psychostimulant therapy and PBT appear to be similar in efficacy according to this meta-regression.
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Affiliation(s)
- Kung-Han Yang
- Department of Applied Mathematics, Chinese Culture University, Taipei, Taiwan
| | - Hsien-Yuan Lane
- Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan,Graduate Institute of Biomedical Sciences, China Medical University Medical College, Taichung, Taiwan,Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan
| | - Yue-Cune Chang
- Department of Mathematics, Tamkang University, Taipei, Taiwan
| | - Ruu-Fen Tzang
- Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan,Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan,Correspondence: Ruu-Fen Tzang, MD, Department of Psychiatry, Mackay Memorial Hospital, Number 92, Sec. 2, Zhong Shan N Road, Taipei 104, Taiwan ()
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Krueger RF, Hobbs KA, Conway CC, Dick DM, Dretsch MN, Eaton NR, Forbes MK, Forbush KT, Keyes KM, Latzman RD, Michelini G, Patrick CJ, Sellbom M, Slade T, South S, Sunderland M, Tackett J, Waldman I, Waszczuk MA, Wright AG, Zald DH, Watson D, Kotov R. Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): II. Externalizing superspectrum. World Psychiatry 2021; 20:171-193. [PMID: 34002506 PMCID: PMC8129870 DOI: 10.1002/wps.20844] [Citation(s) in RCA: 122] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co-occurrence in the modal case, heterogeneity of presentation within dis-orders, and instability of diagnosis within patients. This paper reviews the evidence on the validity and utility of the disinhibited externalizing and antagonistic externalizing spectra of HiTOP, which together constitute a broad externalizing superspectrum. These spectra are composed of elements subsumed within a variety of mental disorders described in recent DSM nosologies, including most notably substance use disorders and "Cluster B" personality disorders. The externalizing superspectrum ranges from normative levels of impulse control and self-assertion, to maladaptive disinhibition and antagonism, to extensive polysubstance involvement and personality psychopathology. A rich literature supports the validity of the externalizing superspectrum, and the disinhibited and antagonistic spectra. This evidence encompasses common genetic influences, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, and treatment response. The structure of these validators mirrors the structure of the phenotypic externalizing superspectrum, with some correlates more specific to disinhibited or antagonistic spectra, and others relevant to the entire externalizing superspectrum, underlining the hierarchical structure of the domain. Compared with traditional diagnostic categories, the externalizing superspectrum conceptualization shows improved utility, reliability, explanatory capacity, and clinical applicability. The externalizing superspectrum is one aspect of the general approach to psychopathology offered by HiTOP and can make diagnostic classification more useful in both research and the clinic.
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Affiliation(s)
| | - Kelsey A. Hobbs
- Department of PsychologyUniversity of MinnesotaMinneapolisMNUSA
| | | | - Danielle M. Dick
- Department of PsychologyVirginia Commonwealth UniversityRichmondVAUSA
| | - Michael N. Dretsch
- US Army Medical Research Directorate ‐ WestWalter Reed Army Institute of Research, Joint Base Lewis‐McChordWAUSA
| | | | - Miriam K. Forbes
- Centre for Emotional Health, Department of PsychologyMacquarie UniversitySydneyNSWAustralia
| | | | | | | | - Giorgia Michelini
- Semel Institute for Neuroscience and Human BehaviorUniversity of California Los AngelesLos AngelesCAUSA
| | | | - Martin Sellbom
- Department of PsychologyUniversity of OtagoDunedinNew Zealand
| | - Tim Slade
- Matilda Centre for Research in Mental Health and Substance UseUniversity of SydneySydneyNSWAustralia
| | - Susan C. South
- Department of Psychological SciencesPurdue UniversityWest LafayetteINUSA
| | - Matthew Sunderland
- Matilda Centre for Research in Mental Health and Substance UseUniversity of SydneySydneyNSWAustralia
| | | | - Irwin Waldman
- Department of PsychologyEmory UniversityAtlantaGAUSA
| | | | | | - David H. Zald
- Department of PsychologyVanderbilt UniversityNashvilleTNUSA
| | - David Watson
- Department of PsychologyUniversity of Notre DameNotre DameINUSA
| | - Roman Kotov
- Department of PsychiatryStony Brook UniversityStony BrookNYUSA
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19th Latest Advances in Psychiatry International Symposium. PROGRESS IN NEUROLOGY AND PSYCHIATRY 2021. [DOI: 10.1002/pnp.710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Lantz S, Fornwall C, Lööf M, Isaksson J. SKILLS - A psychoeducational group programme for children with ADHD. Scand J Psychol 2021; 62:460-467. [PMID: 33982811 DOI: 10.1111/sjop.12727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/18/2021] [Accepted: 02/16/2021] [Indexed: 11/26/2022]
Abstract
Psychoeducation is regarded as a first line of intervention for attention-deficit/hyperactivity disorder (ADHD). Previous studies have been limited to psychoeducation for adult patients or parents of children with ADHD. Therefore, the aim of the present study was to investigate the acceptability and effectiveness of a psychoeducational group intervention for children with ADHD. The two-session psychoeducational intervention, SKILLS, was completed by 125 children (6-12 years) with ADHD and their parents. Self-ratings and parental ratings of ADHD symptoms, functional impairment and attitudes to diagnosis and treatment were collected before and after treatment. Post-treatment client satisfaction and parental responses to an open question about SKILLS were assessed. The data were analyzed using a combination of quantitative and qualitative (content analysis) methods. A majority of the participants expressed satisfaction with the group intervention. The intervention had no effect on symptoms and level of function, although the parents were more positive to their child's diagnosis after the intervention. The parents were positive to the group format and to the opportunity for their children to meet other children with similar symptoms. Parents wished for more interactive elements and more opportunities for children to share experiences. We concluded that the group intervention was accepted by most participants, although more activating exercises and opportunities for interaction between participants should be included. Since the intervention group was not compared with a control group, the results should be interpreted with caution. Future studies should use a randomized control treatment design and investigate the effect on adherence to later treatment.
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Affiliation(s)
- Sofia Lantz
- Department of Neuroscience, Child and Adolescent Psychiatry Unit, Uppsala University, Uppsala, Sweden
| | - Charlotta Fornwall
- Department of Neuroscience, Child and Adolescent Psychiatry Unit, Uppsala University, Uppsala, Sweden
| | - Måns Lööf
- Child & Adolescent Psychiatric Clinic, Gävle, Sweden
| | - Johan Isaksson
- Department of Neuroscience, Child and Adolescent Psychiatry Unit, Uppsala University, Uppsala, Sweden.,Department of Women's and Children's Health, Centre for Psychiatry Research, Karolinska Institute Centre of Neurodevelopmental Disorders (KIND), Karolinska Institute, Stockholm, Sweden
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