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1.
J Clin Psychiatry ; 84(1)2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36652686

RESUMO

Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure.Methods: In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors.Results: We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16).Conclusions: After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations.


Assuntos
Anormalidades Induzidas por Medicamentos , Cardiopatias Congênitas , Gravidez , Recém-Nascido , Feminino , Humanos , Cloridrato de Atomoxetina/efeitos adversos , Estudos de Coortes , Prevalência , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Primeiro Trimestre da Gravidez , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/epidemiologia
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(1): 98-103, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36655671

RESUMO

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.


Assuntos
Cloridrato de Atomoxetina , Transtorno do Deficit de Atenção com Hiperatividade , Citocromo P-450 CYP2D6 , Adulto , Criança , Humanos , Inibidores da Captação Adrenérgica/uso terapêutico , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/uso terapêutico , Monitoramento de Medicamentos , Testes Genéticos , Propilaminas/uso terapêutico , Resultado do Tratamento
3.
Biomolecules ; 12(10)2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36291693

RESUMO

Changes in dopaminergic and noradrenergic transmission are considered to be the underlying cause of attention deficit and hyperactivity disorder (ADHD). Atomoxetine (ATX) is a selective norepinephrine transporter (NET) inhibitor that is currently used for ADHD treatment. In this study, we aimed to evaluate the effect of atomoxetine on the behavior and brain activity of dopamine transporter knockout (DAT-KO) rats, which are characterized by an ADHD-like behavioral phenotype. Prepulse inhibition (PPI) was assessed in DAT-KO and wild type rats after saline and ATX injections, as well as behavioral parameters in the Hebb-Williams maze and power spectra and coherence of electrophysiological activity. DAT-KO rats demonstrated a pronounced behavioral and electrophysiological phenotype, characterized by hyperactivity, increased number of errors in the maze, repetitive behaviors and disrupted PPI, changes in cortical and striatal power spectra and interareal coherence. Atomoxetine significantly improved PPI and decreased repetitive behaviors in DAT-KO rats and influenced behavior of wild-type rats. ATX also led to significant changes in power spectra and coherence of DAT-KO and wild type rats. Assessment of noradrenergic modulation effects in DAT-KO provides insight into the intricate interplay of monoaminergic systems, although further research is still required to fully understand the complexity of this interaction.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Ratos , Animais , Cloridrato de Atomoxetina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Cognição , Norepinefrina/farmacologia , Corpo Estriado
4.
Artigo em Inglês | MEDLINE | ID: mdl-36232180

RESUMO

Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder with three presentations: inattentive, hyperactive/impulsive and combined. These may represent an independent disease entity. Therefore, the therapeutic approach must be focused on their neurobiological, psychological and social characteristics. To date, there is no comprehensive analysis of the efficacy of different treatments for each presentation of ADHD and each stage of development. This is as narrative overview of scientific papers that summarize the most recent findings and identify the most effective pharmacological and psychosocial treatments by ADHD presentation and age range. Evidence suggests that methylphenidate is the safest and most effective drug for the clinical management of children, adolescents and adults. Atomoxetine is effective in preschoolers and maintains similar efficacy to methylphenidate in adults, whereas guanfacine has proven to be an effective monotherapy for adults and is a worthy adjuvant for the management of cognitive symptoms. The psychosocial treatments with the best results in preschoolers are behavioral interventions that include training of primary caregivers. In adolescents, the combination of cognitive and cognitive-behavioral therapies has shown the best results, whereas cognitive-behavioral interventions are the most effective in adults. Pharmacological and psychosocial treatments must be adjusted to the ADHD presentation and its neurocognitive characteristics through the patient's development.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Adolescente , Adulto , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Guanfacina/uso terapêutico , Humanos , Metilfenidato/uso terapêutico
6.
Clin Neuropharmacol ; 45(6): 177-178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093917

RESUMO

OBJECTIVES: Risperidone is an effective drug used for the treatment of irritability in children with autism spectrum disorder (ASD). Atomoxetine (ATX) is a well-tolerated drug used in first-line therapy in children with attention-deficit/hyperactivity disorder (ADHD). However, uncommon adverse effects of risperidone and ATX are a concern among mental health professionals. To our knowledge, this is the first case report of priapism after addition of ATX upon existing treatment with risperidone. METHODS: Written informed consent for publication was obtained from the patient and his parents, and their identities were concealed for ethical reasons. RESULTS: Here, we report a case of priapism as an adverse effect of ATX and risperidone treatment in a 7-year-old boy with ASD and comorbid ADHD. In this case, priapism was not observed with risperidone until ATX was added. CONCLUSIONS: Priapism is a condition viewed as a medical emergency. Although risperidone-induced priapism is a rare phenomenon, it is advised for clinicians to consider the drug interactions in treatment of ASD and ADHD in terms of early diagnosis and intervention.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Priapismo , Criança , Masculino , Humanos , Cloridrato de Atomoxetina/efeitos adversos , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/tratamento farmacológico , Risperidona/efeitos adversos , Inibidores da Captação Adrenérgica/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Priapismo/induzido quimicamente
7.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142172

RESUMO

Attention deficit hyperactivity disorder (ADHD) is one of the most common worldwide mental disorders in children, young and adults. If left untreated, the disorder can continue into adulthood. The abuse of ADHD-related drugs to improve mental performance for studying, working and everyday life is also rising. The potentially high number of subjects with controlled or uncontrolled use of such substances increases the impact of possible side effects. It has been shown before that the early ADHD drug methylphenidate influences bone metabolism negatively. This study focused on the influence of three more recent cognitive enhancers, modafinil, atomoxetine and guanfacine, on the differentiation of mesenchymal stem cells to osteoblasts and on their cell functions, including migration. Human mesenchymal stem cells (hMSCs) were incubated with a therapeutic plasma dosage of modafinil, atomoxetine and guanfacine. Gene expression analyses revealed a high beta-2 adrenoreceptor expression in hMSC, suggesting it as a possible pathway to stimulate action. In bone formation assays, all three cognitive enhancers caused a significant decrease in the mineralized matrix and an early slight reduction of cell viability without triggering apoptosis or necrosis. While there was no effect of the three substances on early differentiation, they showed differing effects on the expression of osterix (OSX), receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in the later stages of osteoblast development, suggesting alternative modes of action. All three substances significantly inhibited hMSC migration. This effect could be rescued by a selective beta-blocker (Imperial Chemical Industries ICI-118,551) in modafinil and atomoxetine, suggesting mediation via beta-2 receptor stimulation. In conclusion, modafinil, atomoxetine and guanfacine negatively influence hMSC differentiation to bone-forming osteoblasts and cell migration through different intracellular pathways.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Nootrópicos , Adulto , Cloridrato de Atomoxetina/farmacologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Diferenciação Celular , Estimulantes do Sistema Nervoso Central/farmacologia , Criança , Guanfacina/farmacologia , Humanos , Ligantes , Metilfenidato/uso terapêutico , Modafinila/farmacologia , Modafinila/uso terapêutico , Nootrópicos/uso terapêutico , Osteoprotegerina/uso terapêutico , Receptor Ativador de Fator Nuclear kappa-B
8.
J Neurosci ; 42(43): 8113-8124, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36109167

RESUMO

Sustained attention describes our ability to keep a constant focus on a given task. This ability is modulated by our physiological state of arousal. Although lapses of sustained attention have been linked with dysregulations of arousal, the underlying physiological mechanisms remain unclear. An emerging body of work proposes that the intrusion during wakefulness of sleep-like slow waves, a marker of the transition toward sleep, could mechanistically account for attentional lapses. This study aimed to expose, via pharmacological manipulations of the monoamine system, the relationship between the occurrence of sleep-like slow waves and the behavioral consequences of sustained attention failures. In a double-blind, randomized-control trial, 32 healthy human male participants received methylphenidate, atomoxetine, citalopram or placebo during four separate experimental sessions. During each session, electroencephalography (EEG) was used to measure neural activity while participants completed a visual task requiring sustained attention. Methylphenidate, which increases wake-promoting dopamine and noradrenaline across cortical and subcortical areas, improved behavioral performance whereas atomoxetine, which increases dopamine and noradrenaline predominantly over frontal cortices, led to more impulsive responses. Additionally, citalopram, which increases sleep-promoting serotonin, led to more missed trials. Based on EEG recording, citalopram was also associated with an increase in sleep-like slow waves. Importantly, compared with a classical marker of arousal such as α power, only slow waves differentially predicted both misses and faster responses in a region-specific fashion. These results suggest that a decrease in arousal can lead to local sleep intrusions during wakefulness which could be mechanistically linked to impulsivity and sluggishness.SIGNIFICANCE STATEMENT We investigated whether the modulation of attention and arousal could not only share the same neuromodulatory pathways but also rely on similar neuronal mechanisms; for example, the intrusion of sleep-like activity within wakefulness. To do so, we pharmacologically manipulated noradrenaline, dopamine, and serotonin in a four-arm, randomized, placebo-controlled trial and examined the consequences on behavioral and electroencephalography (EEG) indices of attention and arousal. We showed that sleep-like slow waves can predict opposite behavioral signatures: impulsivity and sluggishness. Slow waves may be a candidate mechanism for the occurrence of attentional lapses since the relationship between slow-wave occurrence and performance is region-specific and the consequences of these local sleep intrusions are in line with the cognitive functions carried by the underlying brain regions.


Assuntos
Citalopram , Metilfenidato , Masculino , Humanos , Citalopram/farmacologia , Dopamina , Cloridrato de Atomoxetina/farmacologia , Serotonina , Sono/fisiologia , Vigília/fisiologia , Eletroencefalografia/métodos , Atenção , Norepinefrina , Metilfenidato/farmacologia
9.
Methods Mol Biol ; 2547: 427-436, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36068472

RESUMO

ADHD is a common condition in both children and adults. The most prescribed medications for the treatment of ADHD include methylphenidate, mixed amphetamine salts, atomoxetine, guanfacine, and clonidine. While each of these medications have their own distinct pharmacokinetic profile, the extent to which pharmacogenetics effects their pharmacokinetic parameters is best described in atomoxetine, followed by methylphenidate. Atomoxetine is predominantly metabolized by cytochrome p450 2D6 (CYP2D6), while methylphenidate is metabolized by carboxylesterase 1 (CES1). Both CYP2D6 and CES1 have multiple variants resulting in varying levels of enzyme activity; however, to date, the functional consequence of variants and alleles for CYP2D6 is better characterized as compared to CES1. Regarding CYP2D6, individuals who are poor metabolizers prescribed atomoxetine experience up to ten-fold higher exposure as compared to normal metabolizers at comparable dosing. Additionally, individuals prescribed methylphenidate with the rs71647871 variant may experience up to 2.5-fold higher exposure as compared to those without. Having this pharmacogenetic information available may aid clinicians and patients when choosing medications and doses to treat ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Metilfenidato , Adulto , Cloridrato de Atomoxetina/farmacocinética , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP2D6/uso terapêutico , Humanos , Metilfenidato/uso terapêutico , Farmacogenética
10.
Asian J Psychiatr ; 76: 103232, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35987096

RESUMO

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects approximately 2-7 % of children globally and is associated with a myriad of difficulties that have long-term consequences. Most children and adolescents live in low- and middle-income countries (LMICs), but there are few reports and no consolidation of findings on ADHD treatment outcomes in this population. We conducted a review of ADHD treatment literature for children and adolescents living in LMICs. METHODS: Studies were identified using databases (PsychoINFO, Pubmed, MEDLINER, EMBASE, Global Health, Academic Search Complete, Google Scholar). The initial search produced 139 articles. These were filtered for language, title, abstract, and full-text keyword identification to yield a final 20 articles to be included in this review. RESULTS: Reports on outcomes of both psychological and pharmacological treatment were relatively sparse, particularly the former, which mostly referred to parent training and multimodal programs in pre-school children. Most evidence exists for the benefit of methylphenidate-IR with a few reports on other agents, including clonidine, atomoxetine, and lisdexamfetamine. Methylphenidate is the most common agent to treat ADHD in youth in LMICs. Younger age, combined subtype, and comorbid oppositional defiant disorder were associated with poorer treatment outcome. CONCLUSION: Access to treatment for ADHD is overall limited in LMICs and varied among individual countries. Pharmacological treatments were generally more available than psychological interventions. Several barriers including stigma, cost, and lack of resources were reported to impact treatment acceptance. More research in LMICs is needed to improve and expand mental health services in these regions.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Adolescente , Cloridrato de Atomoxetina , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Pré-Escolar , Clonidina/uso terapêutico , Países em Desenvolvimento , Humanos , Metilfenidato/uso terapêutico
11.
J Clin Sleep Med ; 18(12): 2837-2844, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35975547

RESUMO

STUDY OBJECTIVE: Obstructive sleep apnea is a common and serious sleep disorder for which treatment remains challenging due to lack of adherence to approved therapies. Previous pharmacological studies addressing sleep-related upper airway muscle hypotonia suggested that the combination of atomoxetine and oxybutynin is effective in treating obstructive sleep apnea. The current study is with aroxybutynin (AD109), a new enantiomerically pure form of oxybutynin with better safety profile compared to racemic oxybutynin. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study in patients with mild to moderate obstructive sleep apnea. Each received low-dose AD109 (37.5/2.5 mg), high-dose AD109 (75/2.5 mg), and placebo at bedtime across 3 overnight periods in a randomized order. Adverse events were collected by telephone contact with participants during each washout period. The primary endpoint was change in hypoxic burden and secondary endpoint was apnea-hypopnea index. RESULTS: Patients treated with both the high and low doses of AD109 had a statistically significant and clinically meaningful difference from placebo in hypoxic burden. Median [interquartile range] hypoxic burden for participants on placebo was 13.9[4.5-21.9] (%min)/h vs 2.3[0.1-10.5] (%min)/h for patients on the high dose (P < .001) and to 7.3[2-12.5] (%min)/h on the low dose (P < .01). Apnea-hypopnea index went from a median of 13.2[8.0-19.1] events/h on placebo reduced to 5.5[2.2 to 9.6] events/h on the high dose (P < .001) and to 7.8[4-13.7] events/h on the low dose (P < .05). AD109 demonstrated a favorable safety profile. CONCLUSIONS: This study provides additional support that a pharmacological intervention for obstructive sleep apnea, namely the combination of atomoxetine and aroxybutynin, offers promising results. Additional development of this compound and others is warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: AD109 Dose Finding in Mild to Moderate OSA; URL: https://clinicaltrials.gov/ct2/show/NCT04631107; Identifier: NCT04631107. CITATION: Rosenberg R, Abaluck B, Thein S. Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA. J Clin Sleep Med. 2022;18(12):2837-2844.


Assuntos
Antagonistas Muscarínicos , Apneia Obstrutiva do Sono , Humanos , Cloridrato de Atomoxetina/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Estudos Cross-Over , Apneia Obstrutiva do Sono/complicações , Hipóxia/complicações
12.
Respirology ; 27(11): 975-982, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35811347

RESUMO

BACKGROUND AND OBJECTIVE: The combination of the noradrenergic atomoxetine plus the anti-muscarinic oxybutynin acutely increased genioglossus activity and reduced obstructive sleep apnoea (OSA) severity. However, oxybutynin has shorter half-life than atomoxetine and side effects that might discourage long-term usage. Accordingly, we aimed to test the combination of atomoxetine and fesoterodine (Ato-Feso), a newer anti-muscarinic with extended release formulation, on OSA severity and endotypes. METHODS: Twelve subjects with OSA underwent a randomized, double-blind, crossover trial comparing one night of atomoxetine plus fesoterodine (80-4 mg) to placebo. Parameters of OSA severity (e.g., apnoea-hypopnoea index [AHI], nadir oxygen desaturation and hypoxic burden) were calculated from two clinical, in-lab polysomnographic studies. OSA endotypes (including collapsibility per VMIN and arousal threshold) were derived from validated algorithms. RESULTS: Compared to placebo, Ato-Feso did not reduce the AHI (34.2 ± 19.1 vs. 30.1 ± 28.2 events/h, p = 0.493), but reduced the apnoea index (12.9 [28.8] vs. 1.8 [9.1] events/h, median [interquartile range], p = 0.027) and increased nadir desaturation (76.8 [8.0] vs. 82.2 [8.8] %, p = 0.003); a non-significant trend for improved hypoxic burden was observed (52.4 [50.5] vs. 29.7 [78.9] %min/h, p = 0.093). Ato-Feso lowered collapsibility (raised VMIN ; 43.7 [29.8-55.7] vs. 56.8 [43.8-69.8] %VEUPNOEA , mean [CI], p = 0.002), but reduced the arousal threshold (129.3 [120.1-138.6] vs. 116.7 [107.5-126] %VEUPNOEA , p = 0.038). In post hoc analysis, 6/6 patients with milder collapsibility (VMIN > 43%) exhibited OSA resolution (drop in AHI > 50% and residual AHI < 10 events/h) and improved hypoxaemia. CONCLUSION: While inefficacious in unselected patients, Ato-Feso administered for one night suppressed OSA in patients with milder collapsibility. Ato-Feso may hold some promise as an alternative OSA treatment in certain subgroups of individuals.


Assuntos
Apneia Obstrutiva do Sono , Cloridrato de Atomoxetina/farmacologia , Cloridrato de Atomoxetina/uso terapêutico , Compostos Benzidrílicos , Preparações de Ação Retardada/uso terapêutico , Humanos , Ácidos Mandélicos , Oxigênio , Apneia Obstrutiva do Sono/tratamento farmacológico
13.
J Atten Disord ; 26(14): 1822-1832, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35822610

RESUMO

OBJECTIVE: Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research. METHOD: Controlled trials of adult ADHD measuring emotional behavior were included if another study offered a comparable analysis of the same treatment method. Standardized Mean Difference (SMD) of effects were calculated, and the size of effects for emotional and non-emotional ADHD behavior were compared. RESULTS: 13 out of 14 studies of methylphenidate, atomoxetine, and lisdexamfetamine demonstrated significant improvement in emotional behavior measures, with small to high SMDs. The proportional effect on emotional versus non-emotional behavior ranged from 46% to 110% for methylphenidate, 56% to 129% for atomoxetine, and 36% to 96% for lisdexamfetamine. CONCLUSION: Psychopharmacological treatments for ADHD are likely to improve emotional behavior, and available scales are sensitive to these effects. Studies dedicated to treatment of this domain of function can further refine clinical approaches.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Adulto , Humanos , Cloridrato de Atomoxetina/uso terapêutico , Dimesilato de Lisdexanfetamina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Resultado do Tratamento
14.
Res Dev Disabil ; 128: 104275, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35691145

RESUMO

BACKGROUND: Anxiety disorders are among the most common comorbid mental disorders in children and adolescents with attention-deficit hyperactivity disorder (ADHD). While the role of atomoxetine, a non-stimulant medication, is well-established in the management of ADHD symptoms since two decades, there is a dearth of evidence regarding its efficacy in the management of anxiety disorders in children and adolescents with ADHD. AIMS: We aimed to provide insights into (1) the comparative efficacy of atomoxetine in children and adolescents with comorbid ADHD and anxiety disorders, (2) change in severity of anxiety symptoms based on patients', parents', and clinicians' ratings, (3) tolerability and side effects. METHODS: We searched PubMed, EMBASE, and PsycINFO for clinical trials that addressed the efficacy of atomoxetine for anxiety symptoms in children and adolescents with ADHD. All published literature was systematically reviewed. RESULTS: We included four studies, out of which two specifically addressed comorbid ADHD and anxiety disorder. The studies suggested that atomoxetine did not exacerbate and in fact reduced anxiety symptoms in young patients with comorbid ADHD. CONCLUSIONS AND IMPLICATIONS: Overall, atomoxetine demonstrates good efficacy in improving anxiety symptoms in children and adolescents with ADHD. Further studies are needed to shed light on atomoxetine's efficacy for anxiety subtypes in ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Adolescente , Inibidores da Captação Adrenérgica/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/epidemiologia , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Humanos , Propilaminas/uso terapêutico , Resultado do Tratamento
15.
Child Adolesc Psychiatr Clin N Am ; 31(3): 417-435, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35697393

RESUMO

Nonstimulants have an important role when response or tolerability to psychostimulants is poor, when certain comorbid disorders are present, or if patients prefer nonstimulants. Here, we discuss monotherapy and combined treatment of ADHD and review mechanism of action, pharmacokinetics, efficacy, tolerability, and safety of approved, off-label, and pipeline nonstimulants. We present detailed information regarding the 4 FDA-approved nonstimulant medications-the norepinephrine reuptake inhibitors, atomoxetine and viloxazine extended release, and the α-2 adrenergic agonists, clonidine XR and guanfacine XR. We additionally review evidence regarding the off-label use of a variety of other medications. Variability across and within drug classes in nature of response, approach to titration, and temporal characteristics of treatment allow a nuanced treatment approach for individuals with comorbid disorders and complicated clinical presentations. Availability of nonstimulant medications enhances our opportunity to offer personalized treatment of ADHD across the lifespan.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Clonidina/uso terapêutico , Guanfacina/farmacologia , Guanfacina/uso terapêutico , Humanos
16.
Child Adolesc Psychiatr Clin N Am ; 31(3): 469-477, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35697396

RESUMO

A complete and comprehensive medical and psychiatric evaluation is necessary to delineate tic symptoms from attention-deficit/hyperactivity disorder, and to prioritize the most problematic symptoms for intervention. Stimulants are the recommended first-line pharmacotherapy to treat attention-deficit/hyperactivity disorder symptoms in patients with tic disorders. Comprehensive behavioral intervention for tics is an effective behavioral therapy that is generally considered the first-line treatment of persistent tic disorders. α-Agonists can be added to stimulants if tics increase or be used as monotherapy to target attention-deficit/hyperactivity disorder and tics. Atomoxetine is also an excellent option to treat attention-deficit/hyperactivity disorder and tics.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Transtornos de Tique , Tiques , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Comorbidade , Humanos , Transtornos de Tique/tratamento farmacológico , Transtornos de Tique/epidemiologia , Tiques/tratamento farmacológico
17.
Int J Neuropsychopharmacol ; 25(9): 709-719, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-35524732

RESUMO

BACKGROUND: Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanisms have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these 2 medications in alleviating the clinical symptoms and functional impairments observed in ADHD. METHODS: Sixty-seven ADHD and 44 age-matched children with typical development were included and underwent resting-state functional magnetic resonance imaging scans at baseline. Then patients were assigned to MPH, ATX, or untreated subgroups, based on the patients' and their parents' choice, for a 12-week follow-up and underwent a second functional magnetic resonance imaging scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group. RESULTS: Both MPH and ATX normalized the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared with ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, and the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment. CONCLUSIONS: Both MPH and ATX can normalize abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the 2 medications showed shared and unique effects on brain functions to alleviate clinical symptoms and functional impairment.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Inibidores da Captação Adrenérgica/uso terapêutico , Cloridrato de Atomoxetina/farmacologia , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Encéfalo , Estimulantes do Sistema Nervoso Central/farmacologia , Criança , Humanos , Metilfenidato/farmacologia
18.
PLoS Comput Biol ; 18(5): e1010079, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35533200

RESUMO

Apathy is a debilitating feature of many neuropsychiatric diseases, that is typically described as a reduction of goal-directed behaviour. Despite its prevalence and prognostic importance, the mechanisms underlying apathy remain controversial. Degeneration of the locus coeruleus-noradrenaline system is known to contribute to motivational deficits, including apathy. In healthy people, noradrenaline has been implicated in signalling the uncertainty of expectations about the environment. We proposed that noradrenergic deficits contribute to apathy by modulating the relative weighting of prior beliefs about action outcomes. We tested this hypothesis in the clinical context of Parkinson's disease, given its associations with apathy and noradrenergic dysfunction. Participants with mild-to-moderate Parkinson's disease (N = 17) completed a randomised double-blind, placebo-controlled, crossover study with 40 mg of the noradrenaline reuptake inhibitor atomoxetine. Prior weighting was inferred from psychophysical analysis of performance in an effort-based visuomotor task, and was confirmed as negatively correlated with apathy. Locus coeruleus integrity was assessed in vivo using magnetisation transfer imaging at ultra-high field 7T. The effect of atomoxetine depended on locus coeruleus integrity: participants with a more degenerate locus coeruleus showed a greater increase in prior weighting on atomoxetine versus placebo. The results indicate a contribution of the noradrenergic system to apathy and potential benefit from noradrenergic treatment of people with Parkinson's disease, subject to stratification according to locus coeruleus integrity. More broadly, these results reconcile emerging predictive processing accounts of the role of noradrenaline in goal-directed behaviour with the clinical symptom of apathy and its potential pharmacological treatment.


Assuntos
Apatia , Doença de Parkinson , Cloridrato de Atomoxetina/farmacologia , Estudos Cross-Over , Humanos , Norepinefrina , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico
20.
Curr Top Behav Neurosci ; 57: 321-362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35606638

RESUMO

Based on core symptoms of inattention and deficient impulse control, and the identification of effective pharmacotherapies such as amphetamine (AMP; Adderall®), methylphenidate (MPH; Ritalin®), and atomoxetine (ATX; Strattera®), ADHD is a clinical condition which provides opportunity for translational research. Neuropsychological tests such as the 5-Choice and Continuous Performance Tasks, which measure aspects of attention and impulse control in animals and humans, provide scope for both forward (animal to human) and reverse (human to animal) translation. Rodent studies support pro-attentive effects of AMP and MPH and effectiveness in controlling some forms of impulsive behavior. In contrast, any pro-attentive effects of ATX appear to be less consistent, the most reliable effects of ATX are recorded in tests of impulsivity. These differences may account for AMP and MPH being recognized as first-line treatments for ADHD with a higher efficacy relative to ATX. DSM-5 classifies three "presentations" of ADHD: predominantly inattentive type (ADHD-I), predominantly hyperactive/impulsive type (ADHD-HI), or combined (ADHD-C). Presently, it is unclear whether AMP, MPH, or ATX has differential levels of efficacy across these presentation types. Nonetheless, these studies encourage confidence for the forward translation of NCEs in efforts to identify newer pharmacotherapies for ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Monofosfato de Adenosina/uso terapêutico , Animais , Cloridrato de Atomoxetina/farmacologia , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Cognição , Humanos , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Propilaminas/farmacologia , Propilaminas/uso terapêutico
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