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Chen L, Du W. Multidimensional Comparison of Methylphenidate and Atomoxetine in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children, a 12-Week, Open-Label, Head-to-Head Clinical Trial. Psychiatry Investig 2025; 22:140-147. [PMID: 40017277 DOI: 10.30773/pi.2024.0204] [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: 06/24/2024] [Accepted: 10/10/2024] [Indexed: 03/01/2025] Open
Abstract
OBJECTIVE To compare the treatment efficacy of methylphenidate and atomoxetine on core symptoms, behavioral and emotional problems, and executive function in children with attention-deficit/hyperactivity disorder (ADHD). METHODS Sixty children with ADHD diagnosed by the fifth edition Diagnostic and Statistical Manual of Mental Disorders in Tangshan Maternal and Child Health Hospital from 2023 to 2024 were randomly divided into methylphenidate and atomoxetine groups. Core symptoms were assessed using the Parent Swanson, Nolan, and Pelham, Version IV Scale (SNAP-IV) and Integrated Visual and Auditory Continuous Performance Test (IVA-CPT). Behavioral and emotional problems were administered via the Conners Parent Symptom Questionnaire (PSQ) and executive function was evaluated utilizing the Wisconsin Card Sorting Test (WCST) and Digit Span Test (DST). All data were analyzed using SPSS 26.00 to identify discrepancies. RESULTS When contrasted with the methylphenidate and atomoxetine groups at 12 weeks, their mean efficiency was no significant disparity (p>0.05). Notable statistical differences were evident in IVA-CPT, the inattention, hyperactivity-impulsivity of SNAP-IV, and the psychosomatic disorder, anxiety, and hyperactivity-impulsivity of PSQ (p<0.05), yet in hyperactivity index, conduct, and learning difficulties of PSQ (p>0.05). No statistical significance was attributed to DST and the number of completed categories in WCST (p>0.05) but to response errors and perseverative errors (p<0.05). CONCLUSION Although both methylphenidate and atomoxetine are capable of effectively ameliorating ADHD, methylphenidate demonstrates a superior ability to improve core symptoms of ADHD, as well as address conduct problems, cognitive transfer abilities, and frontal lobe function in pediatric patients. Conversely, atomoxetine is the best choice for cases comorbid with anxiety.
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Affiliation(s)
- Lin Chen
- Department of Child Health, Tangshan Maternal and Child Health Hospital, North China University of Science and Technology, Hebei Tangshan, China
| | - Wenran Du
- Department of Child Health, Tangshan Maternal and Child Health Hospital, North China University of Science and Technology, Hebei Tangshan, China
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Seo S, Parr-Brownlie LC, Wicky HE, Bilkey DK, Hughes SM, Oorschot DE. A Risk Factor for Attention Deficit Hyperactivity Disorder Induces Marked Long-Term Anatomical Changes at GABAergic-Dopaminergic Synapses in the Rat Ventral Tegmental Area. Int J Mol Sci 2024; 25:12970. [PMID: 39684680 DOI: 10.3390/ijms252312970] [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: 10/31/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. However, the core biology of the disorder that leads to the hypofunctioning of the cerebral dopaminergic network requires further elucidation. We investigated midbrain synaptic changes in male rats exposed to repeated hypoxia during the equivalent of extreme prematurity, which is a new animal model of the hyperactive/impulsive presentation of ADHD. We used a novel combination of a lentiviral vector, peroxidase-immunonanogold double-labelling, three-dimensional serial section transmission electron microscopy and stereological techniques to investigate the synapses formed between GABAergic axons of the rostromedial tegmental nucleus (RMTg) and dopaminergic neurons of the posterior ventral tegmental area (pVTA). This is a key site that sends extensive dopaminergic projections to the forebrain. We also compared the results to our previous study on a schizophrenia risk factor that produces cerebral hyperdopaminergia. In total, 117 reconstructed synapses were compared. Repeated hypoxic rats had a significantly thicker (22%) and longer (18%) postsynaptic density at RMTg GABAergic-pVTA dopaminergic synapses compared to their controls. These results were opposite to those previously observed in rats exposed to a schizophrenia risk factor. These findings for repeated hypoxic rats suggest that the enhanced inhibition of pVTA dopaminergic neurons may contribute to hypodopaminergia in ADHD motor hyperactivity. Synaptic triads, a key component of pVTA circuitry, were not detected in repeated hypoxic rats, indicating a marked deficit. The current knowledge may guide development in males of novel, site-specific ADHD drugs, which is necessary due to the rising prevalence of ADHD, the chronic nature of ADHD symptoms and the limitations of the currently available medications.
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Affiliation(s)
- Steve Seo
- Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand
- Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand
| | - Louise C Parr-Brownlie
- Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand
- Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand
- Brain Research, Dunedin 9054, New Zealand
| | - Hollie E Wicky
- Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand
- Brain Research, Dunedin 9054, New Zealand
- Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand
| | - David K Bilkey
- Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand
- Department of Psychology, University of Otago, Dunedin 9054, New Zealand
| | - Stephanie M Hughes
- Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand
- Brain Research, Dunedin 9054, New Zealand
- Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand
| | - Dorothy E Oorschot
- Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand
- Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand
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Shen F, Zhou H. Methylphenidate treatment of a Chinese boy with Becker muscular dystrophy combined with attention deficit hyperactivity disorder: a case report. Front Neurosci 2024; 18:1459582. [PMID: 39659883 PMCID: PMC11628498 DOI: 10.3389/fnins.2024.1459582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 11/13/2024] [Indexed: 12/12/2024] Open
Abstract
Background Becker muscular dystrophy (BMD) is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis, caused by mutations in the DMD gene, which encodes dystrophin protein. Different from Duchenne Muscular Dystrophy (DMD), in which dystrophin is completely absent in muscle tissue, while in BMD, the dystrophin gene can express some protein, but not enough. It has also been shown that a proportion of patients with DMD suffer from attention deficit hyperactivity disorder (ADHD), and the use of the stimulant methylphenidate has been suggested for the treatment of patients with DMD in combination with ADHD. However, there are no case reports on the treatment of co-occurring ADHD in BMD. Case presentation The patient was a 9-year-old boy who presented with elevated serum creatine kinase levels and inattention. The magnetic resonance imaging of the thigh muscles of both lower limbs suggested partial fatty infiltration of the gluteus maximus muscle bilaterally, and a novel heterozygous mutation (c.31 + 6 T > C) was identified in the DMD gene by Next Generation Sequencing (NGS) and the sequencing results were verified by using the Sanger method. The child was also diagnosed with co-morbid ADHD after a thorough evaluation and considering this new diagnosis, we started treatment with methylphenidate at a dose of 18 mg/day, and after 6 months of treatment, he showed a significant improvement in his attention span. Conclusion We identified a novel heterozygous mutation in the DMD gene, which will expand the spectrum of pathogenic variants in BMD. Simultaneously, methylphenidate treatment significantly improved attention in children with BMD co-morbid with ADHD, and this study provides value for future therapeutic protocols for BMD combined with ADHD. However, to the best of our knowledge, this is the only reported case report on the treatment of BMD co-morbid ADHD. So further studies are needed to determine the interrelationship between these disorders and their treatment.
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Affiliation(s)
| | - Hui Zhou
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education (MOE), Chengdu, Sichuan, China
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Maji S, Mishra A, Ramasubbu MK, Mohapatra D, Maiti R. Efficacy and safety of monoamine reuptake inhibitors in attention deficit hyperactivity disorder: A Bayesian network meta-analysis. J Psychiatr Res 2024; 176:403-410. [PMID: 38950507 DOI: 10.1016/j.jpsychires.2024.06.048] [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: 09/04/2023] [Revised: 03/03/2024] [Accepted: 06/26/2024] [Indexed: 07/03/2024]
Abstract
The use of first-line drugs in clinical practice for attention deficit hyperactivity disorder (ADHD) is limited by their adverse effects. Many novel monoamine reuptake inhibitors (MRIs) with better safety profiles and comparable efficacy are also being tried for ADHD. This network meta-analysis (NMA) has evaluated the efficacy and safety of MRIs in ADHD. The data was extracted from 31 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases, and clinical trial registries. Quality assessment was performed using the risk of bias assessment tool (RoB2) by Cochrane Collaboration, and the random-effects model was used to estimate the effect size. Standardised mean difference (SMD) and 95% credible interval(95%CrI) were reported for the reduction in ADHD rating scale score. Network geometry was visualised, and node splitting was done for the closed triangles. Meta-regression was done for the duration of therapy. PRISMA-NMA guidelines were followed in selecting, analyzing, and reporting findings. The drugs showing significant reduction on the ADHD rating scale as compared to placebo are bupropion (SMD: 0.33; 95%CrI: 0.60,-0.059), dasotraline(SMD: 0.49; 95%CrI: 0.82,-0.16), venlafaxine(SMD: 0.71; 95%CrI: 1.3,-0.15), viloxazine(SMD: 0.45; 95%CrI: 0.77,-0.12). Other drugs (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no better than placebo in reducing symptom severity of ADHD. The efficacy of none of the drugs was found to be significantly different as compared to methylphenidate. Among all, duloxetine (OR:15; 95%CrI:1.8130) showed significantly more treatment-emergent adverse events than methylphenidate. In conclusion, venlafaxine, viloxazine, and bupropion are the most efficacious MRIs for ADHD symptom reduction as compared to placebo with high certainty of evidence.
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Affiliation(s)
- Shampa Maji
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
| | - Archana Mishra
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
| | - Mathan Kumar Ramasubbu
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
| | - Debadatta Mohapatra
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
| | - Rituparna Maiti
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
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Thongseiratch T, Chalermphol K, Traipidok P, Charleowsak P. Promoting Medication Adherence in Children with Attention Deficit Hyperactivity Disorder: A Mixed-Methods Systematic Review with Meta-analysis and Qualitative Comparative Analysis. J Atten Disord 2024; 28:139-150. [PMID: 38006238 DOI: 10.1177/10870547231211021] [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: 11/26/2023]
Abstract
OBJECTIVE To evaluate the efficacy of ADHD medication adherence interventions and explore the pathways to effectiveness. METHODS A systematic review was conducted using multiple databases to identify relevant randomized controlled trials (RCTs). Pooled effect sizes were calculated for medication adherence and ADHD symptom outcomes. Qualitative Comparative Analysis (QCA) was used to identify pathways to effectiveness. RESULTS Six RCTs were included. The interventions significantly improved medication adherence (OR = 2.39, 95% CI [1.19, 4.79]) and ADHD symptoms (Hedges' g = -0.96, 95% CI [-1.38, -0.54]). Multi-regression analysis showed a positive relationship between medication adherence and ADHD symptom reduction. QCA revealed two paths for effectiveness: (1) Presence of ADHD drug education and absence of reminder and (2) Presence of tracking and absence of reminder. CONCLUSION ADHD medication adherence interventions have a positive impact on both medication adherence and ADHD symptoms. Interventions should consider including ADHD drug education or tracking to maximize effectiveness.
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Affiliation(s)
- Therdpong Thongseiratch
- Child Development Unit, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
| | - Kanokphorn Chalermphol
- Child Development Unit, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
| | - Pathrada Traipidok
- Child Development Unit, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
| | - Pattra Charleowsak
- Child Development Unit, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
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Ince N, Sari SA. Atomoxetine-Associated Maculopapular Rash: A Case Report. J Clin Psychopharmacol 2023; 43:539-541. [PMID: 37930210 DOI: 10.1097/jcp.0000000000001776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2023]
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Ryst E, Childress A. An updated safety review of the current drugs for managing ADHD in children. Expert Opin Drug Saf 2023; 22:1025-1040. [PMID: 37843488 DOI: 10.1080/14740338.2023.2271392] [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: 02/27/2023] [Accepted: 10/12/2023] [Indexed: 10/17/2023]
Abstract
INTRODUCTION Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent condition that causes persistent problems with attention and/or hyperactivity-impulsivity and often results in significant impairment when left untreated. Medications for this disorder continue to evolve and provide new treatment options. Ongoing review of related medication safety and tolerability remains an important task for prescribers. AREAS COVERED This manuscript provides an updated safety review of medications used to treat ADHD in children and adolescents. PubMed and OneSearch online databases were utilized to search for literature relevant to the topic of ADHD medications and safety. Clinical trials of medications used to treat ADHD, systematic reviews and meta-analyses, and articles covering specific safety issues (adverse or unfavorable events) such as cardiovascular effects, seizures, impact on growth, depression, suicidal ideation, substance use disorders, psychosis, and tics are described. EXPERT OPINION Available pharmacologic treatments for ADHD have favorable efficacy, safety and tolerability and allow many patients to achieve significant improvement of their symptoms. Despite the availability of multiple stimulant and non-stimulant formulations, some individuals with ADHD may not tolerate available medications or attain satisfactory improvement. To satisfy unmet clinical needs, ADHD pharmaceutical research with stimulant and nonstimulant formulations targeting dopamine, norepinephrine, and novel receptors is ongoing.
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Affiliation(s)
- Erika Ryst
- College of Education and Human Development, University of Nevada, Reno, USA
| | - Ann Childress
- Center for Psychiatry and Behavioral Medicine, Inc, Las Vegas, NV, USA
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Storebø OJ, Storm MRO, Pereira Ribeiro J, Skoog M, Groth C, Callesen HE, Schaug JP, Darling Rasmussen P, Huus CML, Zwi M, Kirubakaran R, Simonsen E, Gluud C. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev 2023; 3:CD009885. [PMID: 36971690 PMCID: PMC10042435 DOI: 10.1002/14651858.cd009885.pub3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
BACKGROUND Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015. OBJECTIVES To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to March 2022. In addition, we checked reference lists and requested published and unpublished data from manufacturers of methylphenidate. SELECTION CRITERIA We included all randomised clinical trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. The search was not limited by publication year or language, but trial inclusion required that 75% or more of participants had a normal intellectual quotient (IQ > 70). We assessed two primary outcomes, ADHD symptoms and serious adverse events, and three secondary outcomes, adverse events considered non-serious, general behaviour, and quality of life. DATA COLLECTION AND ANALYSIS Two review authors independently conducted data extraction and risk of bias assessment for each trial. Six review authors including two review authors from the original publication participated in the update in 2022. We used standard Cochrane methodological procedures. Data from parallel-group trials and first-period data from cross-over trials formed the basis of our primary analyses. We undertook separate analyses using end-of-last period data from cross-over trials. We used Trial Sequential Analyses (TSA) to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the GRADE approach. MAIN RESULTS We included 212 trials (16,302 participants randomised); 55 parallel-group trials (8104 participants randomised), and 156 cross-over trials (8033 participants randomised) as well as one trial with a parallel phase (114 participants randomised) and a cross-over phase (165 participants randomised). The mean age of participants was 9.8 years ranging from 3 to 18 years (two trials from 3 to 21 years). The male-female ratio was 3:1. Most trials were carried out in high-income countries, and 86/212 included trials (41%) were funded or partly funded by the pharmaceutical industry. Methylphenidate treatment duration ranged from 1 to 425 days, with a mean duration of 28.8 days. Trials compared methylphenidate with placebo (200 trials) and with no intervention (12 trials). Only 165/212 trials included usable data on one or more outcomes from 14,271 participants. Of the 212 trials, we assessed 191 at high risk of bias and 21 at low risk of bias. If, however, deblinding of methylphenidate due to typical adverse events is considered, then all 212 trials were at high risk of bias. PRIMARY OUTCOMES methylphenidate versus placebo or no intervention may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -0.88 to -0.61; I² = 38%; 21 trials; 1728 participants; very low-certainty evidence). This corresponds to a mean difference (MD) of -10.58 (95% CI -12.58 to -8.72) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points). The minimal clinically relevant difference is considered to be a change of 6.6 points on the ADHD-RS. Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 0.91 (CI 0.31 to 2.68). SECONDARY OUTCOMES methylphenidate may cause more adverse events considered non-serious versus placebo or no intervention (RR 1.23, 95% CI 1.11 to 1.37; I² = 72%; 35 trials 5342 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 1.22 (CI 1.08 to 1.43). Methylphenidate may improve teacher-rated general behaviour versus placebo (SMD -0.62, 95% CI -0.91 to -0.33; I² = 68%; 7 trials 792 participants; very low-certainty evidence), but may not affect quality of life (SMD 0.40, 95% CI -0.03 to 0.83; I² = 81%; 4 trials, 608 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS The majority of our conclusions from the 2015 version of this review still apply. Our updated meta-analyses suggest that methylphenidate versus placebo or no-intervention may improve teacher-rated ADHD symptoms and general behaviour in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. Methylphenidate may be associated with an increased risk of adverse events considered non-serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilised. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognised adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomised trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes.
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Affiliation(s)
- Ole Jakob Storebø
- Psychiatric Research Unit, Region Zealand Psychiatry, Slagelse, Denmark
- Child and Adolescent Psychiatric Department, Region Zealand, Roskilde, Denmark
- Department of Psychology, University of Southern Denmark, Odense, Denmark
| | | | | | - Maria Skoog
- Clinical Study Support, Clinical Studies Sweden - Forum South, Lund, Sweden
| | - Camilla Groth
- Pediatric Department, Herlev University Hospital, Herlev, Denmark
| | | | | | | | | | - Morris Zwi
- Islington Child and Adolescent Mental Health Service, Whittington Health, London, UK
| | - Richard Kirubakaran
- Cochrane India-CMC Vellore Affiliate, Prof. BV Moses Centre for Evidence Informed Healthcare and Health Policy, Christian Medical College, Vellore, India
| | - Erik Simonsen
- Research Unit, Mental Health services, Region Zealand Psychiatry, Roskilde, Denmark
- Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital ─ Rigshospitalet, Copenhagen, Denmark
- Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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Karabulut E, Yazıcı HG, Özkan S. Maximizing Pharmacological Treatment Adherence of Children and Adolescents: A Randomized Controlled Study. J Psychosoc Nurs Ment Health Serv 2023; 61:16-24. [PMID: 35858190 DOI: 10.3928/02793695-20220705-02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The aim of the current randomized controlled study was to evaluate treatment adherence of children and adolescents who visited an outpatient psychiatry clinic and started medication for the first time, with telehealth application. This study was performed with parents of patients who visited the clinic from October 1, 2020, to March 31, 2021. Data were collected using a personal information form, Medication Control Form, and Morisky Medication Adherence Scale via telephone after verbal and written consent were obtained. It was found that 96.7% of participants in the experimental group had high medication adherence, whereas 93.3% of participants in the control group had low medication adherence. Results show that telehealth application is effective in maximizing adherence to treatment among children and adolescents. [Journal of Psychosocial Nursing and Mental Health Services, 61(1), 16-24.].
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Zheng Q, Duan D, Xu J, Wang X, Ge Y, Xiong L, Yang J, Wulayin S, Luo X. Comparative safety of multiple doses of erythropoietin for the treatment of traumatic brain injury: A systematic review and network meta-analysis. Front Neurol 2022; 13:998320. [PMID: 36582613 PMCID: PMC9793776 DOI: 10.3389/fneur.2022.998320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/21/2022] [Indexed: 12/15/2022] Open
Abstract
Introduction Over the past few decades, advances in traumatic brain injury (TBI) pathology research have dynamically enriched our knowledge. Therefore, we aimed to systematically elucidate the safety and efficacy of erythropoietin (EPO) dosing regimens in patients with TBI. Methods Data search included PubMed, the Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for related research published before July 2022. The network meta-analysis was conducted using ADDIS 1.16.8, and the CINeMA tool was used to assess the quality level of evidence. Results A total of six RCTs involving 981 patients were included in the network meta-analysis. EPO did not significantly reduce mortality in patients with TBI, but its risk of death decreased with increasing dosage (odds ratio (OR) of 12,000u vs. placebo = 0.98, 95% CI: 0.03-40.34; OR of group 30,000u vs. placebo = 0.56, 95% CI: 0.06-5.88; OR of 40,000u vs. placebo = 0.35, 95% CI: 0.01-9.43; OR of 70,000u vs. placebo = 0.29, 95% CI: 0.01-9.26; OR of group 80,000u vs. placebo = 0.22, 95% CI: 0.00-7.45). A total of three studies involving 739 patients showed that EPO did not increase the incidence of deep vein thrombosis in patients with TBI. However, the risk tended to rise as the dosage increased. Another two studies demonstrated that EPO did not increase the incidence of pulmonary embolism. The quality of evidence for all outcomes was low to moderate. Conclusion Although the efficacy of EPO was not statistically demonstrated, we found a trend toward an association between EPO dosage and reduced mortality and increased embolic events in patients with TBI. More high-quality original studies should be conducted to obtain strong evidence on the optimal dosage of EPO. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=272500. The study protocol was registered with PROSPERO (CRD42021272500).
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Affiliation(s)
- Qingyong Zheng
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China,Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, Gansu, China,Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China
| | - Dan Duan
- Evidence-Based Nursing Center, School of Nursing, Lanzhou University, Lanzhou, Gansu, China
| | - Jianguo Xu
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China
| | - Xing Wang
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Yonggui Ge
- Department of Rehabilitation, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Lu Xiong
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China
| | - Jingjing Yang
- The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Saimire Wulayin
- The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Xiaofeng Luo
- School of Public Health, Lanzhou University, Lanzhou, Gansu, China,*Correspondence: Xiaofeng Luo
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Alkalay S, Dan O. Effect of short-term methylphenidate on social impairment in children with attention deficit/hyperactivity disorder: systematic review. Child Adolesc Psychiatry Ment Health 2022; 16:93. [PMID: 36443766 PMCID: PMC9706974 DOI: 10.1186/s13034-022-00526-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 11/14/2022] [Indexed: 11/30/2022] Open
Abstract
Attention Deficit/Hyperactivity disorder (ADHD) is one of the most common disorders in school-age children. In addition to learning difficulties associated with the disorder's core symptoms of inattention and hyperactivity, children with ADHD display substantial social impairments. Methylphenidate (MPH) in formulations such as Ritalin or Concerta mitigates inattention and hyperactivity, but the effects of the therapy on social behavior in children with ADHD are not clear. This review aims to determine the effectiveness of short term (up to 6 months) MPH treatment on three domains of social skills in children aged 6-14 with ADHD: (i) Recognition of nonverbal emotional expressions, which are a marker of inherent (unlearned) social understanding, (ii) theory of mind (ToM) components that relate to learned cognition and social communication, and (iii) social competence in everyday environments. 15 relevant studies were identified based on inclusion/exclusion criteria. The results show mixed effects: the overall social performance as evaluated by parents, teachers or peers, and some components of ToM, were found to improve following a weeks-long course of MPH treatment. However, the effects of the medication are less clear when evaluating momentary/nonverbal social responses such as reactions to emotional facial expressions. While the findings of this review indicate that an MPH medication regime of order weeks to months could improve, to a degree, social impairment in children with ADHD, more studies are required to identify the medications' mechanism and confirm such a conclusion.
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Affiliation(s)
- Sarit Alkalay
- Department of Psychology, The Center for Psychobiological Research, Max Stern Jezreel Valley Academic College, P.O.B. 72, 10806, Sede Nahum, Israel.
| | - Orrie Dan
- Department of Psychology, The Center for Psychobiological Research, Max Stern Jezreel Valley Academic College, P.O.B. 72, 10806 Sede Nahum, Israel
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Xu XP, Wang W, Wan S, Xiao CF. Convergence mechanism of mindfulness intervention in treating attention deficit hyperactivity disorder: Clues from current evidence. World J Clin Cases 2022; 10:9219-9227. [PMID: 36159418 PMCID: PMC9477656 DOI: 10.12998/wjcc.v10.i26.9219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/26/2022] [Accepted: 07/29/2022] [Indexed: 02/05/2023] Open
Abstract
This paper reviews the underlying evidence for various aspects of the convergence mechanism of mindfulness intervention in attention deficit hyperactivity disorder (ADHD). There may be compatibility among various ADHD remission models and the therapeutic mechanism of mindfulness intervention in ADHD may be mainly via the convergence mechanism. However, neuroimaging-based analysis of the mechanisms of mindfulness intervention in treating ADHD is lacking. Differences in the efficacy of various subtypes of mindfulness intervention, and corresponding specific imaging changes need further investigation. Future research may focus on the neuroimaging features of specific mindfulness intervention subtypes.
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Affiliation(s)
- Xin-Peng Xu
- Universal Scientific Education and Research Network, Beijing 100088, China
| | - Wei Wang
- Beijing Anding Hospital, Capital Medical University, Beijing 100088, China
| | - Song Wan
- Universal Scientific Education and Research Network, Beijing 100088, China
| | - Chun-Feng Xiao
- Universal Scientific Education and Research Network, Beijing 100088, China
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13
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Methylphenidate Use for Emotional Dysregulation in Children and Adolescents with ADHD and ADHD and ASD: A Naturalistic Study. J Clin Med 2022; 11:jcm11102922. [PMID: 35629047 PMCID: PMC9142913 DOI: 10.3390/jcm11102922] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/10/2022] [Accepted: 05/20/2022] [Indexed: 02/05/2023] Open
Abstract
Emotional dysregulation (ED) is common in attention-deficit/hyperactivity disorder (ADHD). Nonetheless, research on ADHD in children with autism spectrum disorder (ASD) and ADHD is still ongoing. Several studies suggest that methylphenidate (MPH) may be effective for ED in ADHD, while there is not enough evidence about its use in ASD with comorbid ADHD. This naturalistic study aims to investigate the effectiveness of immediate- and extended-release MPH in the treatment of ED in 70 children and adolescents (6–18 years), with a diagnosis of ADHD (n = 41) and of ASD with comorbid ADHD (n = 29), using the Child Behavior Checklist—Attention/Aggressive/Anxious (CBCL-AAA). Their parents completed the CBCL twice—first during the summer medication-free period, that is, at least one month after drug interruption; and again after three months of treatment restart. Results demonstrate that MPH is associated with a statistically significant reduction in ED in ADHD and ASD, without substantial adverse events, supporting the use of psychostimulants for the treatment of ED in these neurodevelopmental disorders.
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14
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Herrera-Morales WV, Ramírez-Lugo L, Cauich-Kumul R, Murillo-Rodríguez E, Núñez-Jaramillo L. Personalization of pharmacological treatments for ADHD: Why it is advisable and possible options to achieve it. Curr Top Med Chem 2022; 22:1236-1249. [DOI: 10.2174/1568026622666220509155413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 02/08/2022] [Accepted: 02/18/2022] [Indexed: 11/22/2022]
Abstract
Abstract:
Attention-deficit hyperactivity disorder is a neurodevelopmental disorder diagnosed primarily in children, although it is also present in adults. Patients present inattention, impulsivity, and hyperactivity symptoms that create difficulties in their daily lives. Pharmacological treatment with stimulants or non-stimulants is used most commonly to reduce ADHD symptoms. Although generally effective and safe, pharmacological treatments have different effects among patients, including lack of response and adverse reactions. The reasons for these differences are not fully understood, but they may derive from the highly diverse etiology of ADHD. Strategies to guide optimal pharmacological treatment selection on the basis of individual patients’ physiological markers are being developed. In this review, we describe the main pharmacological ADHD treatments used and their main drawbacks. We present alternatives under study that would allow the customization of pharmacological treatments to overcome these drawbacks and achieve more reliable improvement of ADHD symptoms.
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Affiliation(s)
- Wendy Verónica Herrera-Morales
- Departamento de Ciencias Médicas. División de Ciencias de la Salud. Universidad de Quintana Roo. Chetumal, Quintana Roo. México
| | - Leticia Ramírez-Lugo
- Instituto de Fisiología Celular. Universidad Nacional Autónoma de México. Ciudad de México. México
| | - Roger Cauich-Kumul
- Departamento de Ciencias Farmaceúticas. División de Ciencias de la Salud. Universidad de Quintana Roo. Chetumal, Quintana Roo. México
| | - Eric Murillo-Rodríguez
- Laboratorio de Neurociencias Moleculares e Integrativas. Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab Mérida, México
- Intercontinental Neuroscience Research Group, Mérida, Yucatán, México
| | - Luis Núñez-Jaramillo
- Departamento de Ciencias Médicas. División de Ciencias de la Salud. Universidad de Quintana Roo. Chetumal, Quintana Roo. México
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15
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Balasundaram MK, Singh A. Viloxazine for attention-deficit hyperactivity disorder: a new formulation for a new indication. DRUGS & THERAPY PERSPECTIVES 2022. [DOI: 10.1007/s40267-022-00892-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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16
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Siebelink NM, Kaijadoe SPT, van Horssen FM, Holtland JNP, Bögels SM, Buitelaar JK, Speckens AEM, Greven CU. Mindfulness for Children With ADHD and Mindful Parenting (MindChamp): A Qualitative Study on Feasibility and Effects. J Atten Disord 2021; 25:1931-1942. [PMID: 32727260 PMCID: PMC8427809 DOI: 10.1177/1087054720945023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Objective: We describe qualitative results on facilitators and barriers to participating in a family mindfulness-based intervention (MBI) for youth with ADHD and their parents and perceived effects on child and parent. Method: Sixty-nine families started the 8-week protocolized group-based MBI called "MYmind." After the MBI, individual semi-structured interviews were conducted with a purposive sample of parents (n = 20), children (n = 17, ages 9-16 years), and mindfulness teachers (n = 3). Interviews were analyzed using Grounded Theory. Results: Facilitators and barriers regarding contextual factors (e.g., time investment), MBI characteristics (e.g., parallel parent-child training), and participant characteristics (e.g., ADHD-symptoms) are described. Perceived effects were heterogeneous: no/adverse effects, awareness/insight, acceptance, emotion regulation/reactivity, cognitive functioning, calmness/relaxation, relational changes, generalization. Conclusion: MYmind can lead to a variety of transferable positively perceived effects beyond child ADHD-symptom decrease. Recommendations on MYmind participant inclusion, program characteristics, mindfulness teachers, and evaluating treatment efficacy are provided.
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Affiliation(s)
- Nienke M. Siebelink
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands,Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
| | | | - Fylis M. van Horssen
- Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
| | | | - Susan M. Bögels
- Department of Developmental Psychology & Research Institute of Child Development and Education, University of Amsterdam, The Netherlands
| | - Jan K. Buitelaar
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands,Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
| | - Anne E. M. Speckens
- Radboudumc Center for Mindfulness, Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Corina U. Greven
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands,Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands,Institute of Psychiatry, Psychology and Neuroscience, Social, Genetic and Developmental Psychiatry Centre, King’s College London, UK,Corina U. Greven, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
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17
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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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18
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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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19
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Efficacy and Safety of Medication for Attention-Deficit Hyperactivity Disorder in Children and Adolescents with Common Comorbidities: A Systematic Review. Neurol Ther 2021; 10:499-522. [PMID: 34089145 PMCID: PMC8571469 DOI: 10.1007/s40120-021-00249-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 04/09/2021] [Indexed: 11/25/2022] Open
Abstract
Introduction Comorbid psychiatric conditions in children and adolescents with attention-deficit hyperactivity disorder (ADHD) occur frequently, complicate management, and are associated with substantial burden on patients and caregivers. Very few systematic reviews have assessed the efficacy and safety of medications for ADHD in children and adolescents with comorbidities. Of those that were conducted, most focused on a particular comorbidity or medication. In this systematic literature review, we summarize the efficacy and safety of treatments for children and adolescents with ADHD and comorbid autism spectrum disorders, oppositional defiant disorder, Tourette’s disorder and other tic disorders, generalized anxiety disorder, and major depressive disorder. Methods We searched MEDLINE, Embase, and ClinicalTrials.gov (to October 2019) for studies of patients (aged < 18 years) with an ADHD diagnosis and the specified comorbidities treated with amphetamines, methylphenidate and derivatives, atomoxetine (ATX), and guanfacine extended-release (GXR). For efficacy, placebo-controlled randomized controlled trials (RCTs) or meta-analyses of RCTs were eligible for inclusion; for safety, all study types were eligible. The primary efficacy outcome measure was ADHD Rating Scale IV (ADHD-RS-IV) total score. Results Of 2177 publications/trials retrieved, 69 were included in this systematic literature review (5 meta-analyses, 37 placebo-controlled RCTs, 16 cohort studies, 11 case reports). A systematic narrative synthesis is provided because insufficient data were retrieved to combine ADHD-RS-IV total scores or effect sizes. Effect sizes for ADHD-RS-IV total scores were available for ten RCTs and ranged from 0.46 to 1.0 for ATX and from 0.92 to 2.0 for GXR across comorbidities. The numbers and types of adverse events in children with comorbidities were consistent with those in children without comorbidities, but treatment should be individualized to ensure children can tolerate the lowest effective dose. Conclusion Limited information is available from placebo-controlled RCTs on the efficacy (by ADHD-RS-IV) or safety of medication in children with ADHD and psychiatric comorbidities. Further studies are required to support evidence-based drug selection for these populations. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-021-00249-0.
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20
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Rodrigues R, Lai MC, Beswick A, Gorman DA, Anagnostou E, Szatmari P, Anderson KK, Ameis SH. Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry 2021; 62:680-700. [PMID: 32845025 DOI: 10.1111/jcpp.13305] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/03/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta-analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation. METHODS We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha-2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random-effects model. RESULTS Twenty-five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent-rated: standardized mean difference [SMD] = -.63, 95%CI = -.95,-.30; teacher-rated: SMD = -.81, 95%CI = -1.43,-.19) and inattention (parent-rated: SMD = -.36, 95%CI = -.64,-.07; teacher-rated: SMD = -.30, 95%CI = -.49,-.11). Atomoxetine reduced inattention (parent-rated: SMD = -.54, 95%CI = -.98,-.09; teacher/investigator-rated: SMD = -0.38, 95%CI = -0.75, -0.01) and parent-rated hyperactivity (parent-rated: SMD = -.49, 95%CI = -.76,-.23; teacher-rated: SMD = -.43, 95%CI = -.92, .06). Indirect evidence for significant reductions in hyperactivity with second-generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events. CONCLUSIONS Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long-term continuation is undertaken to help guide clinical decision-making regarding treatment of co-occurring ADHD symptoms in children and youth with ASD.
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Affiliation(s)
- Rebecca Rodrigues
- Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Meng-Chuan Lai
- The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.,Centre for Brain and Mental Health, Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.,Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.,Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.,Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Adam Beswick
- Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Daniel A Gorman
- Centre for Brain and Mental Health, Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.,Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Evdokia Anagnostou
- Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, Department of Pediatrics, University of Toronto, Toronto, ON, Canada
| | - Peter Szatmari
- The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.,Centre for Brain and Mental Health, Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.,Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Kelly K Anderson
- Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.,Department of Psychiatry, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada
| | - Stephanie H Ameis
- The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.,Centre for Brain and Mental Health, Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.,Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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21
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Chronic Administrations of Guanfacine on Mesocortical Catecholaminergic and Thalamocortical Glutamatergic Transmissions. Int J Mol Sci 2021; 22:ijms22084122. [PMID: 33923533 PMCID: PMC8073983 DOI: 10.3390/ijms22084122] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/06/2021] [Accepted: 04/14/2021] [Indexed: 01/07/2023] Open
Abstract
It has been established that the selective α2A adrenoceptor agonist guanfacine reduces hyperactivity and improves cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD). The major mechanisms of guanfacine are considered to involve the activation of the postsynaptic α2A adrenoceptor of glutamatergic pyramidal neurons in the frontal cortex, but the effects of chronic guanfacine administration on catecholaminergic and glutamatergic transmissions associated with the orbitofrontal cortex (OFC) are yet to be clarified. The actions of guanfacine on catecholaminergic transmission, the effects of acutely local and systemically chronic (for 7 days) administrations of guanfacine on catecholamine release in pathways from the locus coeruleus (LC) to OFC, the ventral tegmental area (VTA) and reticular thalamic-nucleus (RTN), from VTA to OFC, from RTN to the mediodorsal thalamic-nucleus (MDTN), and from MDTN to OFC were determined using multi-probe microdialysis with ultra-high performance liquid chromatography. Additionally, the effects of chronic guanfacine administration on the expression of the α2A adrenoceptor in the plasma membrane fraction of OFC, VTA and LC were examined using a capillary immunoblotting system. The acute local administration of therapeutically relevant concentrations of guanfacine into the LC decreased norepinephrine release in the OFC, VTA and RTN without affecting dopamine release in the OFC. Systemically, chronic administration of therapeutically relevant doses of guanfacine for 14 days increased the basal release of norepinephrine in the OFC, VTA, RTN, and dopamine release in the OFC via the downregulation of the α2A adrenoceptor in the LC, OFC and VTA. Furthermore, systemically, chronic guanfacine administration did not affect intrathalamic GABAergic transmission, but it phasically enhanced thalamocortical glutamatergic transmission. The present study demonstrated the dual actions of guanfacine on catecholaminergic transmission-acute attenuation of noradrenergic transmission and chronic enhancement of noradrenergic transmission and thalamocortical glutamatergic transmission. These dual actions of guanfacine probably contribute to the clinical effects of guanfacine against ADHD.
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22
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Scholle O, Kollhorst B, Riedel O, Bachmann CJ. First-Time Users of ADHD Medication Among Children and Adolescents in Germany: An Evaluation of Adherence to Prescribing Guidelines Based on Claims Data. Front Psychiatry 2021; 12:653093. [PMID: 33935837 PMCID: PMC8081976 DOI: 10.3389/fpsyt.2021.653093] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 03/11/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Drug utilization studies based on real-world data are vital for the identification of potentially needed improvements to rational prescribing. This is particularly important for the pharmacological treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD) due to the associated potential side effects and the frequent use. Whereas prevalent use is well-characterized, studies on first-time use of ADHD medication are scarce. This study aimed to evaluate off-label prescribing in first-time users of ADHD medication among children and adolescents in Germany based on three criteria: (i) lack of a documented ADHD diagnosis; (ii) first-time pharmacological treatment with a second-line drug; and (iii) patient age below 6 years. Methods: Based on German claims data, we included children and adolescents aged 0-17 years with a first-time dispensation of any ADHD medication in the period 2015-2017. These first-time users were characterized with regard to sex, age, specialty of the prescribing physician, documentation of an ADHD diagnosis, psychiatric hospitalization, psychiatric comorbidities, and history of other psychopharmacological drugs at first-time use. Results: The study population comprised 18,703 pediatric first-time users of ADHD medication. Of these, 9.8% had no documented ADHD diagnosis. Most of the ADHD drug users received first-line ADHD pharmacotherapy (methylphenidate, atomoxetine), whereas 2.6% were prescribed second-line ADHD medication (lisdexamfetamine, guanfacine, dexamfetamine, multiple ADHD drugs) as first drug. Overall, 1.2% of first-time users were aged below 6 years. A total of 12.7% of the study population met any off-label criterion. Conclusions: About 13% of pediatric first-time users of ADHD medication in Germany received an off-label pharmacotherapy at first-time use. Prescribing ADHD medication without a confirmed ADHD diagnosis was the most common of the three assessed off-label criteria. Off-label prescribing regarding drug choice and age of patients only occurred in a small percentage of initial pharmacological ADHD treatment. Our results suggest the need for improvement in rational prescribing, especially with regard to diagnostic requirements.
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Affiliation(s)
- Oliver Scholle
- Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany
| | - Bianca Kollhorst
- Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany
| | - Oliver Riedel
- Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany
| | - Christian J Bachmann
- Department of Child & Adolescent Psychiatry, University Hospital Ulm, Ulm, Germany
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23
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Fu D, Wu DD, Guo HL, Hu YH, Xia Y, Ji X, Fang WR, Li YM, Xu J, Chen F, Liu QQ. The Mechanism, Clinical Efficacy, Safety, and Dosage Regimen of Atomoxetine for ADHD Therapy in Children: A Narrative Review. Front Psychiatry 2021; 12:780921. [PMID: 35222104 PMCID: PMC8863678 DOI: 10.3389/fpsyt.2021.780921] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 12/28/2021] [Indexed: 12/12/2022] Open
Abstract
Atomoxetine, a selective norepinephrine (NE) reuptake inhibitor, was approved for attention deficit/hyperactivity disorder (ADHD) treatment in children, adolescents and adults. We searched the database PubMed/MEDLINE (2000 to October 1, 2021). Only publications in English were considered. Atomoxetine inhibits the presynaptic norepinephrine transporter (NET), preventing the reuptake of NE throughout the brain along with inhibiting the reuptake of dopamine in specific brain regions such as the prefrontal cortex (PFC). The novel mechanism of atomoxetine also includes several new brain imaging studies and animal model studies. It is mainly metabolized by the highly polymorphic drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6). Atomoxetine is effective and generally well tolerated. ADHD is often accompanied by multiple comorbidities. A series of studies have been published suggesting that atomoxetine is effective in the treatment of ADHD symptoms for children with various types of comorbidity. In some cases, it is possible that atomoxetine may have a positive influence on the symptoms of comorbidities. Atomoxetine can be administered either as a single daily dose or split into two evenly divided doses, and has a negligible risk of abuse or misuse. The latest guideline updated that clinical dose selection of atomoxetine was recommended based on both CYP2D6 genotype and the peak concentration. To have a more comprehensive understanding of atomoxetine, this review sets the focus on the mechanism, clinical efficacy and dosage regimen in detail, and also touches on those studies regarding adverse reactions of atomoxetine.
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Affiliation(s)
- Di Fu
- Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China.,School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Dan-Dan Wu
- Department of Children Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Hong-Li Guo
- Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Ya-Hui Hu
- Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Ying Xia
- Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Xing Ji
- Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Wei-Rong Fang
- School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yun-Man Li
- School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Jing Xu
- Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Feng Chen
- Department of Pharmacy, Pharmaceutical Sciences Research Center, Children's Hospital of Nanjing Medical University, Nanjing, China
| | - Qian-Qi Liu
- Department of Children Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China
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Najib J, Didenko E, Meleshkina D, Yusupov K, Maw K, Ramnarain J, Tabassum M. Review of lisdexamfetamine dimesylate in children and adolescents with attention deficit/hyperactivity disorder. Curr Med Res Opin 2020; 36:1717-1735. [PMID: 32845786 DOI: 10.1080/03007995.2020.1815002] [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: 10/23/2022]
Abstract
OBJECTIVE Lisdexamfetamine dimesylate is a stimulant prodrug with low abuse and diversion potential that is used in treatment of attention deficit hyperactivity disorder (ADHD) in children, adolescents and adults. This current literature review article aims to examine safety and efficacy of LDX in children and adolescents for the treatment of ADHD based on currently available data. METHODS Relevant English language articles were identified through computerized searches of the MEDLINE database (PubMed and EMBASE) and clinical trials registry up to January 2020 using the following search terms: lisdexamfetamine dimesylate, pro-drug stimulant, attention-deficit and hyperactivity disorders, ADHD, safety, efficacy, children, adolescents, Vyvanse. Forty-two articles were reviewed, 34 of which were included into this review, selected by the limit "clinical trials". This article represents the pharmacological profile, efficacy and safety data of LDX for the treatment of ADHD in children and adolescents. RESULTS The collection of studies reviewed identified that LDX was both safe and efficacious in the treatment of ADHD. The most commonly exhibited side effects were appetite suppression, weight loss, headache and insomnia. In comparison to placebo, LDX significantly improved ADHD symptoms and overall quality of life in children and adolescents. In comparison to atomoxetine, LDX showed statistically significant improvements in inattention, impulsivity, and activities of daily living. In comparison to OROS-MPH and placebo, LDX and OROS-MPH showed improvements with the CGI-I score, and ADHD-RS-IV, however, LDX was superior. CONCLUSION Patients have seen statistically significant improvements in their ADHD symptomatology in the classroom environment, health related quality of life, and their overall behavior in comparison to placebo, atomoxetine, and OROS-MPH. However, clinical judgment should be utilized when prescribing LDX due to patient specific needs and the side effect profile.
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Affiliation(s)
- Jadwiga Najib
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
- Departments of Pharmacy and Psychiatry, Mount Sinai West Hospital Center, New York, NY, USA
| | - Ekaterina Didenko
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | - Daria Meleshkina
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | - Kamila Yusupov
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | - Kateryna Maw
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | - Justin Ramnarain
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
| | - Maliha Tabassum
- Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA
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25
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Machado YDC, Lopes GDA, Souza TT, da Silva JN, Silva MAR, Miranda DM. Benefit of methylphenidate use in a patient with attention deficit hyperactivity disorder (ADHD) and heart disease: a case report and literature review. Psychiatry Res 2020; 290:113156. [PMID: 32505930 DOI: 10.1016/j.psychres.2020.113156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 05/28/2020] [Accepted: 05/29/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Yuri de Castro Machado
- Molecular Medicine Department of the Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Gabriela de Andrade Lopes
- Molecular Medicine Department of the Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Tchayra Tatiane Souza
- Molecular Medicine Department of the Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Júlia Neves da Silva
- Molecular Medicine Department of the Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Marco Aurélio Romano Silva
- Molecular Medicine Department of the Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Débora Marques Miranda
- Molecular Medicine Department of the Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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26
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Yektaş Ç, Tufan AE, Sarıgedik E. Sleep habits of children diagnosed with attention/ deficit/ hyperactivity disorder and effects of treatment on sleep related parameters. Asian J Psychiatr 2020; 52:102045. [PMID: 32361211 DOI: 10.1016/j.ajp.2020.102045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 03/20/2020] [Accepted: 03/25/2020] [Indexed: 11/27/2022]
Abstract
This study aimed to evaluate the baseline sleep habits of children with ADHD and the effects of treatment with methylphenidate (MPH) and atomoxetine (ATX) on sleep parameters. Treatment naive children with clinically normal intelligence diagnosed with ADHD were enrolled in the study. Children were treated naturalistically with MPH and ATX. Treatments were started at 0.5 mg/ kg/ day and titrated weekly to a maximum of 1.2 mg/ kg/ day. The daily equivalent dose was calculated according to clinician toolkits of Utah Academy of Child and Adolescent Psychiatry. DSM-IV Based Screening and Assessment Scale for Disruptive Behavior Disorders- Parent form (DBSASDBD) and Clinical Global Impression Scale were used to assess ADHD symptoms and Children's Sleep Habits Questionnaire (CSHQ)- Short Form was used to assess the sleep habits and problems before and after the treatment. Both MPH and ATX reduced symptom severity of ADHD in all domains and also reduced total CSHQ scores with similar effect sizes. (0.7 for MPH vs. 0.8 for ATX). The rate of clinically significant sleep problems at baseline was 93.5 %. At the end-point, 83.9 % of the sample still displayed clinically significant sleep problems while none of the children were judged to have moderate-severe sleep problems. Our results suggest that both ATX and MPH may selectively improve different sleep domains in children with ADHD. Studies using standardized dosing schemes for longer durations and evaluating sleep with objective measurements may clarify the differential effects of treatments on sleep among children with ADHD.
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Affiliation(s)
- Çiğdem Yektaş
- Duzce University Faculty of Medicine, Child and Adolescent Psychiatry Department, Turkey.
| | - Ali Evren Tufan
- Acıbadem University Faculty of Medicine, Child and Adolescent Psychiatry Department, Turkey
| | - Enes Sarıgedik
- Duzce University Faculty of Medicine, Child and Adolescent Psychiatry Department, Turkey
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27
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Young JW, Roberts BZ, Breier M, Swerdlow NR. Amphetamine improves rat 5-choice continuous performance test (5C-CPT) irrespective of concurrent low-dose haloperidol treatment. Psychopharmacology (Berl) 2020; 237:1959-1972. [PMID: 32318751 DOI: 10.1007/s00213-020-05511-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 03/26/2020] [Indexed: 12/22/2022]
Abstract
RATIONALE Cognitive dysfunction mediates functional impairment in patients with schizophrenia, necessitating the timely development of pro-cognitive therapeutics. An important initial step in this process is to establish what, if any, pro-cognitive agents and associated mechanisms can be identified using cross-species translational paradigms. For example, attentional deficits-a core feature of schizophrenia-can be measured across species using the 5-choice continuous performance test (5C-CPT). The psychostimulant, amphetamine, improves human and rodent 5C-CPT performance. OBJECTIVE Here, we tested whether amphetamine would similarly improve 5C-CPT performance in the presence of dopamine D2 receptor blockade, since pro-cognitive treatments in schizophrenia would virtually always be used in conjunction with D2 receptor antagonists. METHODS We established the dose-response effects of amphetamine (0, 0.1, 0.3, or 1.0 mg/kg) and haloperidol (0, 3.2, 10, or 32 μg/kg) on 5C-CPT performance in Long Evans rats, and then tested an amphetamine (0.3 mg/kg) × haloperidol (10 μg/kg) interaction; the low dose was chosen because higher doses exerted deleterious non-specific effects on performance. RESULTS Amphetamine improved 5C-CPT performance in poorly performing rats by increasing target detection, independent of haloperidol pretreatment. CONCLUSIONS The pro-attentional effects of amphetamine were most likely mediated by dopamine release at D1-family receptors, since they persisted in the presence of acute D2 blockade. Alternative explanations for these findings are also discussed, as are their potential implications for future pro-cognitive therapeutics in schizophrenia.
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Affiliation(s)
- Jared W Young
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA. .,Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
| | - Benjamin Z Roberts
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA
| | - Michelle Breier
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA
| | - Neal R Swerdlow
- Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA
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28
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Skin Picking Successfully Treated With Atomoxetine in Comorbid Skin Picking and Attention-Deficit/Hyperactivity Disorder: A Case Report. Clin Neuropharmacol 2020; 43:114-115. [PMID: 32541332 DOI: 10.1097/wnf.0000000000000393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
"Skin picking disorder" (SPD: also known as neurotic excoriation, psychogenic excoriation, or dermatillomania) is classified in the "obsessive-compulsive and related disorders" category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and characterized by unintentional, repetitive skin picking behaviors. Atomoxetine is a selective noradrenaline reuptake inhibitor used in the treatment of attention-deficit/hyperactivity disorder (ADHD). In this case report, we present a 9-year-old girl with the comorbid diagnosis of ADHD and SPD treated successfully with atomoxetine. To our knowledge, this is the first report of skin picking treated with atomoxetine in a patient with ADHD. We discussed possible explanations of mechanisms. Further studies are required on the effectiveness of atomoxetine for the treatment of SPD in the presence and absence of comorbid ADHD.
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29
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Fu C, Wu T, Shu Q, Song A, Jiao Y. Acupuncture therapy on postoperative nausea and vomiting in abdominal operation: A Bayesian network meta analysis. Medicine (Baltimore) 2020; 99:e20301. [PMID: 32501976 PMCID: PMC7306321 DOI: 10.1097/md.0000000000020301] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 04/15/2020] [Accepted: 04/16/2020] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Postoperative nausea and vomiting (PONV) is a common complication after surgery. However, drugs cannot prevent it completely, and acupuncture therapy shows the potential in preventing PONV, yet the best choice hasn't been demonstrated. OBJECTIVE This network meta analysis aimed to evaluate the effectiveness of different acupuncture therapies used for preventing PONV in abdominal operation. METHODS Authors searched articles from PubMed/Medline, Cochrane library, Web of Science, Ebsco and Ovid/Embase, and established database from setup time to June 2019. Quality evaluation of included studies was performed with Cochrane risk-of-bias tool (ROB 2.0). Pairwise and network meta analysis were conducted by RevMan and Addis respectively. RESULTS Twenty studies with 2862 patients were included in this research. Pairwise meta analysis shows that compared with placebo, transcutaneous electric nerve stimulation had lower risk of postoperative nausea (PON) (odds ratio (OR) = 0.42, 95%confidence interval (CI): 0.30-0.60), postoperative vomiting (POV) (OR = 0.53, 95%CI: 0.36-0.78), PONVs (OR = 0.46, 95%CI: 0.31-0.68), and postoperative rescue (POR) (OR = 0.61, 95%CI: 0.41-0.90), Capsicum had lower risk of PON (OR = 0.16, 95%CI: 0.09-0.28), PONVs (OR = 0.23, 95%CI: 0.12-0.45), Acupressure had lower risk of POV (OR = 0.42, 95%CI: 0.25-0.70), POR (OR = 0.42, 95%CI: 0.27-0.64). In network meta analysis, compared with usual care, the probability rank suggested that Acupoint Injection showed lowest risk of PON (OR = 0.02, 95%CI: 0.00-0.11), POV (OR = 0.06, 95%CI: 0.01-0.49), Usual care for PONVs (OR = 0.31, 95%CI: 0.13-0.75), and Capsicum for POR (OR = 0.39, 95%CI: 0.07-2.33). Further study should be carried out to verify this result. CONCLUSION Both pairwise and network meta analysis showed acupuncture therapy was superior to placebo and usual care. Different acupuncture therapy regimens may have advantages in different aspects. And compared with POV, PON seems easier to control. Research results may provide guidance for the prevention of PONV.Systematic review registration: PROSPERO CRD42019147556.
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Affiliation(s)
- Chengwei Fu
- Hubei University of Traditional Chinese Medicine
- Zhuji People's Hospital of Zhejiang Province, Zhuji, China
| | - Tong Wu
- Hubei University of Traditional Chinese Medicine
| | - Qing Shu
- Zhongnan Hospital of Wuhan University
| | - Aiqun Song
- Hubei Provincial Hospital of Traditional Chinese Medicine
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan
| | - Yang Jiao
- Hubei Provincial Hospital of Traditional Chinese Medicine
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan
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30
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Koonrungsesomboon K, Koonrungsesomboon N. The Effects of Methylphenidate Treatment on Child Growth in Thai Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol 2020; 30:189-197. [PMID: 31841645 DOI: 10.1089/cap.2019.0115] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objectives: To determine the effects of methylphenidate treatment on child growth in Thai pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Methods: The medical records of children and adolescents with ADHD, between 5 and 18 years of age, who received pharmacological treatment with methylphenidate as a sole psychiatric medication for ≥1 year between 2001 and 2018 at the Rajanagarindra Institute of Child Development, Thailand, were retrospectively reviewed. Data on anthropometric parameters and methylphenidate use were extracted. Height and weight were converted to age- and gender-corrected standard scores (z-scores) using norms from the Thai pediatric population. Changes in height and weight z-scores were assessed using a paired t-test or one-way repeated measures ANOVA with the Bonferroni correction. Results: In this retrospective observational study, 911 children and adolescents were eligible, with the mean age of 95.0 ± 19.5 months at baseline, the cumulative duration of methylphenidate treatment of 39.4 ± 23.5 months, and the average daily dosage of 14.1 ± 6.2 mg/day. Comparative analysis found no statistically significant change in height z-scores between baseline and last recorded measurement (mean difference = 0.0017, confidence interval [95% CI] = -0.0004 to 0.0038, p = 0.107), while a slight, but significant increase in weight z-scores was observed (mean difference = 0.0271, 95% CI = 0.0179-0.0362, p < 0.001). Longitudinal analysis observed that weight z-scores were significantly decreased during the first year of therapy, but regained in the second year and continued to increase in subsequent years of therapy. Conclusion: Treatment with methylphenidate in our cohort of Thai pediatric patients with ADHD was not associated with growth deficits, except for a slightly significant decrease in weight during the first year of therapy.
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Affiliation(s)
| | - Nut Koonrungsesomboon
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Musculoskeletal Science and Translational Research Center, Chiang Mai University, Chiang Mai, Thailand
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31
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Adverse Drug Reactions Related to Mood and Emotion in Pediatric Patients Treated for Attention Deficit/Hyperactivity Disorder: A Comparative Analysis of the US Food and Drug Administration Adverse Event Reporting System Database. J Clin Psychopharmacol 2020; 39:386-392. [PMID: 31205193 DOI: 10.1097/jcp.0000000000001058] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Attention deficit/hyperactivity disorder (ADHD) can be comorbid with frequent anxiety and mood disorders, as well as emotional symptoms (anxiety, irritability, mood lability). These may also be triggered by drugs and appear as adverse drug reactions (ADRs). METHODS We mined data from the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database, focused on methylphenidate, atomoxetine, amphetamine, lisdexamfetamine, and their derivatives. We collected reports of ADRs connected with mood or emotional symptoms in pediatric patients, excluding drug abuse/accidents. Reporting odds ratios (RORs) were calculated and compared between drug classes and children/adolescents. RESULTS We collected 6176 ADRs of interest of which 59% occurred in children. Atomoxetine accounted for 50.7% of reports, methylphenidate for 32.5%, lisdexamfetamine for 14.2%, and amphetamine for 2.6%. Irritability, anxiety, obsessive thoughts, depressed mood, and euphoria scored significant RORs for all drugs, overall with an increasing risk from methylphenidate to atomoxetine, lisdexamfetamine, and amphetamine. Apathy regarded mostly atomoxetine, and crying regarded all drugs except methylphenidate. Several age-based differences were found. Notably, affect lability hit only adolescents. All drugs scored significant self-injury RORs, except lisdexamfetamine in adolescents, with an increasing risk from methylphenidate to lisdexamfetamine, atomoxetine, and amphetamine. For suicidality, all drugs had significant RORs in children, and methylphenidate was better than atomoxetine and lisdexamfetamine. In adolescents, only methylphenidate and atomoxetine scored significant RORs. CONCLUSIONS We conclude that real-world data from the US Food and Drug Administration Adverse Event Reporting System are consistent with previous evidence from meta-analyses. They support a hierarchy of drug safety for several ADRs (except self-injury/suicidality) with methylphenidate as safest, followed by atomoxetine, lisdexamfetamine, and amphetamine last. Self-injury and suicidality RORs were overall higher in children.
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32
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Vasconcelos LPB, Vasconcelos MC, Nunes MDCP, Teixeira AL. Sydenham’s chorea: an update on pathophysiology, clinical features and management. Expert Opin Orphan Drugs 2019. [DOI: 10.1080/21678707.2019.1684259] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Luiz Paulo Bastos Vasconcelos
- Postgraduate Course of Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Marcelle Cristina Vasconcelos
- Postgraduate Course of Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Maria Do Carmo Pereira Nunes
- Postgraduate Course of Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Antonio Lucio Teixeira
- Postgraduate Course of Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Neuropsychiatry Program, UT Health Science Center, Houston, TX, USA
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Therapeutic effects of methylphenidate for attention-deficit/hyperactivity disorder in children with borderline intellectual functioning or intellectual disability: A systematic review and meta-analysis. Sci Rep 2019; 9:15908. [PMID: 31685858 PMCID: PMC6828952 DOI: 10.1038/s41598-019-52205-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 10/07/2019] [Indexed: 01/24/2023] Open
Abstract
Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a first-line treatment for ADHD, however no previous meta-analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability (ID) or borderline intellectual functioning. The PubMed/MEDLINE, Cochrane CENTRAL and ScienceDirect databases were systematically searched from inception through 2018/7/15 for clinical studies that investigated the effects of methylphenidate in children with ADHD and ID. A random-effects model meta-analysis was used for data synthesis. Eight studies (average Jadad score = 2.5) enrolling 242 participants receiving methylphenidate and 181 participants receiving placebo were included. The meta-analysis showed that methylphenidate led to a significant improvement in ADHD symptoms relative to placebo (Hedges’ g = 0.878, p < 0.001). Meta-regression analysis pointed to an association between the dose of methylphenidate and overall improvement in ADHD severity (slope = 1.334, p < 0.001). Finally, there was no significant difference in drop-out rate [odds ratio (OR) = 1.679, p = 0.260] or rate of treatment discontinuation due to adverse events (OR = 4.815, p = 0.053) between subjects receiving methylphenidate and those taking placebos. Our study suggests that methylphenidate retains its efficacy in children with ADHD and borderline intellectual functioning or ID.
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Stewart A, Davis GL, Gresch PJ, Katamish RM, Peart R, Rabil MJ, Gowrishankar R, Carroll FI, Hahn MK, Blakely RD. Serotonin transporter inhibition and 5-HT 2C receptor activation drive loss of cocaine-induced locomotor activation in DAT Val559 mice. Neuropsychopharmacology 2019; 44:994-1006. [PMID: 30578419 PMCID: PMC6462012 DOI: 10.1038/s41386-018-0301-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Revised: 11/19/2018] [Accepted: 12/15/2018] [Indexed: 11/18/2022]
Abstract
Dopamine (DA) signaling dysfunction is believed to contribute to multiple neuropsychiatric disorders including attention-deficit/hyperactivity disorder (ADHD). The rare DA transporter (DAT) coding substitution Ala559Val found in subjects with ADHD, bipolar disorder and autism, promotes anomalous DA efflux in vitro and, in DAT Val559 mice, leads to increased reactivity to imminent handling, waiting impulsivity, and enhanced motivation for reward. Here, we report that, in contrast to amphetamine and methylphenidate, which induce significant locomotor activation, cocaine administration to these mice elicits no locomotor effects, despite retention of conditioned place preference (CPP). Additionally, cocaine fails to elevate extracellular DA. Given that amphetamine and methylphenidate, unlike cocaine, lack high-affinity interactions with the serotonin (5-HT) transporter (SERT), we hypothesized that the lack of cocaine-induced hyperlocomotion in DAT Val559 mice arises from SERT blockade and augmented 5-HT signaling relative to cocaine actions on wildtype animals. Consistent with this idea, the SERT blocker fluoxetine abolished methylphenidate-induced locomotor activity in DAT Val559 mice, mimicking the effects seen with cocaine. Additionally, a cocaine analog (RTI-113) with greater selectivity for DAT over SERT retains locomotor activation in DAT Val559 mice. Furthermore, genetic elimination of high-affinity cocaine interactions at SERT in DAT Val559 mice, or specific inhibition of 5-HT2C receptors in these animals, restored cocaine-induced locomotion, but did not restore cocaine-induced elevations of extracellular DA. Our findings reveal a significant serotonergic plasticity arising in the DAT Val559 model that involves enhanced 5-HT2C signaling, acting independently of striatal DA release, capable of suppressing the activity of cocaine-sensitive motor circuits.
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Affiliation(s)
- Adele Stewart
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA
| | - Gwynne L. Davis
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA ,0000 0001 2264 7217grid.152326.1Neuroscience Graduate Program, Vanderbilt University, Nashville, TN USA
| | - Paul J. Gresch
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA ,0000 0004 0635 0263grid.255951.fBrain Institute, Florida Atlantic University, Jupiter, FL USA
| | - Rania M. Katamish
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA
| | - Rodeania Peart
- 0000 0004 0635 0263grid.255951.fWilkes Honors College, Florida Atlantic University, Jupiter, FL USA
| | - Maximilian J. Rabil
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA
| | - Raajaram Gowrishankar
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA ,0000 0001 2264 7217grid.152326.1Neuroscience Graduate Program, Vanderbilt University, Nashville, TN USA ,0000 0001 2264 7217grid.152326.1International Scholars Program, Vanderbilt University, Nashville, TN USA
| | - F. Ivy Carroll
- 0000000100301493grid.62562.35Research Triangle Institute, Research Triangle Park, NC USA
| | - Maureen K. Hahn
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA ,0000 0004 0635 0263grid.255951.fBrain Institute, Florida Atlantic University, Jupiter, FL USA
| | - Randy D. Blakely
- 0000 0004 0635 0263grid.255951.fDepartment of Biomedical Science, Florida Atlantic University, Jupiter, FL USA ,0000 0004 0635 0263grid.255951.fBrain Institute, Florida Atlantic University, Jupiter, FL USA
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35
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Sierawska A, Prehn-Kristensen A, Moliadze V, Krauel K, Nowak R, Freitag CM, Siniatchkin M, Buyx A. Unmet Needs in Children With Attention Deficit Hyperactivity Disorder-Can Transcranial Direct Current Stimulation Fill the Gap? Promises and Ethical Challenges. Front Psychiatry 2019; 10:334. [PMID: 31156480 PMCID: PMC6531921 DOI: 10.3389/fpsyt.2019.00334] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 04/29/2019] [Indexed: 12/21/2022] Open
Abstract
Attention deficit hyperactivity disorder (ADHD) is a disorder most frequently diagnosed in children and adolescents. Although ADHD can be effectively treated with psychostimulants, a significant proportion of patients discontinue treatment because of adverse events or insufficient improvement of symptoms. In addition, cognitive abilities that are frequently impaired in ADHD are not directly targeted by medication. Therefore, additional treatment options, especially to improve cognitive abilities, are needed. Because of its relatively easy application, well-established safety, and low cost, transcranial direct current stimulation (tDCS) is a promising additional treatment option. Further research is needed to establish efficacy and to integrate this treatment into the clinical routine. In particular, limited evidence regarding the use of tDCS in children, lack of clear translational guidelines, and general challenges in conducting research with vulnerable populations pose a number of practical and ethical challenges to tDCS intervention studies. In this paper, we identify and discuss ethical issues related to research on tDCS and its potential therapeutic use for ADHD in children and adolescents. Relevant ethical issues in the tDCS research for pediatric ADHD center on safety, risk/benefit ratio, information and consent, labeling problems, and nonmedical use. Following an analysis of these issues, we developed a list of recommendations that can guide clinicians and researchers in conducting ethically sound research on tDCS in pediatric ADHD.
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Affiliation(s)
- Anna Sierawska
- Division of Biomedical Ethics, Institute of Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Alexander Prehn-Kristensen
- Department of Child and Adolescent Psychiatry and Psychotherapy, Centre for Integrative Psychiatry, School of Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Vera Moliadze
- Institute of Medical Psychology and Medical Sociology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Kerstin Krauel
- Department of Child and Adolescent Psychiatry and Psychotherapy, University of Magdeburg, Magdeburg, Germany
| | | | - Christine M Freitag
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany
| | - Michael Siniatchkin
- Institute of Medical Psychology and Medical Sociology, Christian-Albrechts-University of Kiel, Kiel, Germany.,Clinic for Child and Adolescent Psychiatry and Psychotherapy, Medical Center Bethel, Bielefeld, Germany
| | - Alena Buyx
- Institute for History and Ethics in Medicine Medical School, Technical University of Munich, Munich, Germany
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36
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Faltinsen EG, Storebø OJ, Gluud C. Methodological concerns with network meta-analysis on drugs for attention deficit hyperactivity disorder. Eur Child Adolesc Psychiatry 2019; 28:145-146. [PMID: 29744668 DOI: 10.1007/s00787-018-1164-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 05/04/2018] [Indexed: 10/16/2022]
Affiliation(s)
| | - Ole Jakob Storebø
- Psychiatric Research Unit, Region Zealand Psychiatry, Slagelse, Denmark
- Department of Psychology, University of Southern Denmark, Odense, Denmark
| | - Christian Gluud
- The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
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37
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Al Khalifah R, Florez ID, Guyatt G, Thabane L. Network meta-analysis: users' guide for pediatricians. BMC Pediatr 2018; 18:180. [PMID: 29843665 PMCID: PMC5975630 DOI: 10.1186/s12887-018-1132-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 04/30/2018] [Indexed: 11/23/2022] Open
Abstract
Background Network meta-analysis (NMA) is a powerful analytic tool that allows simultaneous comparison between several management/treatment alternatives even when direct comparisons of the alternatives (such as the case in which treatments are compared against placebo and have not been compared against each other) are unavailable. Though there are still a limited number of pediatric NMAs published, the rapid increase in NMAs in other areas suggests pediatricians will soon be frequently facing this new form of evidence summary. Discussion Evaluating the NMA evidence requires serial judgments on the creditability of the process of NMA conduct, and evidence quality assessment. First clinicians need to evaluate the basic standards applicable to any meta-analysis (e.g. comprehensive search, duplicate assessment of eligibility, risk of bias, and data abstraction). Then evaluate specific issues related to NMA including precision, transitivity, coherence, and rankings. Conclusions In this article we discuss how clinicians can evaluate the credibility of NMA methods, and how they can make judgments regarding the quality (certainty) of the evidence. We illustrate the concepts using recent pediatric NMA publications.
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Affiliation(s)
- Reem Al Khalifah
- Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada. .,Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism King Saud University, Riyadh, Saudi Arabia.
| | - Ivan D Florez
- Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.,Department of Pediatrics, Universidad de Antioquia, Medellín, Colombia
| | - Gordon Guyatt
- Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.,Department of Medicine, McMaster University, Hamilton, Canada
| | - Lehana Thabane
- Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.,Department of Pediatrics and Anesthesia, McMaster University, Hamilton, ON, Canada
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