The acute effect of methylphenidate in Brazilian male children and adolescents with ADHD: A randomized clinical trial

Szobot, Cláudia Maciel; Ketzer, Carla R.; Parente, Maria Alice de Mattos Pimenta; Biederman, Joseph; Rohde, Luís Augusto

doi:10.1177/108705470400800201

Cited by 25 publications

(9 citation statements)

References 23 publications

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“…Subjects were tested twice; the second T.O.V.A. test was preformed under the influence of methylphenidate and therefore these scores are usually higher since methylphenidate improves performance [Szobot et al, 2004; Boonstra et al, 2005; Huang et al, 2007] (Supplementary Table V). All subjects were treatment‐naïve and receive 0.3–1 mg kg of drug, at the methylphenidate (MPH) phase.…”

Section: Methodsmentioning

confidence: 99%

Association between trypotphan hydroxylase 2, performance on a continuance performance test and response to methylphenidate in ADHD participants

Manor

Laiba

Eisenberg

et al. 2008

American J of Med Genetics Pt B

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The main objective of this study was to examine neuropsychological mechanisms mediating the association between tryptophan hydroxylase 2 (TPH2) and attention deficit hyperactivity disorder (ADHD). A continuous performance test (T.O.V.A.) was administered to 344 participants diagnosed with DSM IV ADHD who were also genotyped for eight TPH2 intronic SNPs. Association between TPH2 (single SNPs and haplotypes), ADHD, and performance on the T.O.V.A. were tested using robust family-based association tests as implemented in two statistical genetic programs: UNPHASED and PBAT. Association was only observed between an eight locus haplotype and ADHD DSM IV combined type III (global P = 0.036). Robust association was observed between TPH2 single SNPs (and haplotypes) and performance on the T.O.V.A., especially Errors of Omission (eight locus haplotypes, global P = 0.038). Significant associations were also observed between TPH2 and improvement (before-after scores) in T.O.V.A. Total Response Variability scores following acute methylphenidate challenge (eight locus haplotypes, global P = 0.009). Using the MFBAT program, significant multivariate association was observed between single SNPs and haplotypes [eight locus haplotypes and all four T.O.V.A. variables (PBAT-GEE P = 0.013)]. The two most common TPH2 eight locus haplotypes were in a Yin Yang configuration and the Yang haplotype was the risk haplotype for both DSM IV ADHD and deficits in neuropsychological performance. The current investigation shows that risk for ADHD conferred by TPH2 variants is partially mediated by serotonergic mechanisms impacting some facets of executive function. Importantly, improvement in T.O.V.A. performance, especially on Response Time Variability, following methylphenidate was also associated with TPH2.

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Section: Methodsmentioning

confidence: 99%

Association between trypotphan hydroxylase 2, performance on a continuance performance test and response to methylphenidate in ADHD participants

Manor

Laiba

Eisenberg

et al. 2008

American J of Med Genetics Pt B

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“…The three cardinal symptoms are hyperactivity, inattention and impulsivity (Biederman and Faraone, 2005). The psychostimulant methylphenidate, a substance of first choice in the treatment of ADHD with the remarkable effect size of about 1.0 in different patient groups (Szobot et al ., 2004; Findling et al ., 2007a), is an inhibitor of the presynaptic dopamine transporter (DAT). It is still under discussion whether alterations of the dopaminergic system are the primary pathophysiological cause for ADHD symptoms or the sequelae of other underlying neurobiological mechanisms such as hyperactivity in the glutamatergic system (Carrey et al ., 2007; Lulé et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations

Ludolph

Udvardi

Schaz

et al. 2010

British J Pharmacology

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Background and purpose:There is increasing evidence that not only the monoaminergic but also the glutamatergic system is involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Hyperactivity of glutamate metabolism might be causally related to a hypoactive state in the dopaminergic system. Atomoxetine, a selective noradrenaline reuptake inhibitor, is the first non-stimulant approved for the treatment of this disorder. Here we have evaluated the effects of atomoxetine on glutamate receptors in vitro. Experimental approach: The whole-cell configuration of the patch-clamp technique was used to analyse the effect of atomoxetine on N-methyl-D-aspartate (NMDA) receptors in cultured rodent cortical and hippocampal neurons as well as on NMDA receptors heterologously expressed in human TsA cells. Key results: Atomoxetine blocked NMDA-induced membrane currents. Half-maximal inhibition emerged at about 3 mM which is in the range of clinically relevant concentrations found in plasma of patients treated with this drug. The inhibition was voltage-dependent, indicating an open-channel blocking mechanism. Furthermore, the inhibitory potency of atomoxetine did not vary when measured on NMDA receptors from different brain regions or with different subunit compositions. Conclusions and implications:The effective NMDA receptor antagonism by atomoxetine at low micromolar concentrations may be relevant to its clinical effects in the treatment of ADHD. Our data provide further evidence that altered glutamatergic transmission might play a role in ADHD pathophysiology.

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“…Several studies have demonstrated an improvement in performance of children with ADHD in intelligence tests, after the use of methylphenidate (Barkley, 2002;Campbell, Douglas, & Morgenstern, 1971;Szobot, Ketzer, Parente, Biederman, & Rohde, 2004). However, when it comes to tasks aimed at evaluating the process of development, as is the case of Piagetian tasks, is the medication producing effects, at least immediate effects, in the development of these children's cognitive structuring?…”

Section: Discussionmentioning

confidence: 99%

Considerations About Psychological Development of Children With ADHD (Attention Deficit Hyperactivity Disorder)

Folquitto¹,

Rodrigues²,

Andrade³

et al. 2014

JPR

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Piaget's theory of psychological development can contribute to a better understanding of ADHD (attention deficit hyperactivity disorder). The assumption is that children with ADHD present deficits in the development of the construction of operational notions, such as space-time conceptions and causality. Sixty-nine children (aged 6 to 12) were divided into two groups: children with ADHD and children without diagnosis. According to Piaget's clinical interview, Piagetian tasks were applied. The clinical sample was sub-divided into children who used methylphenidate and non-medicated children. ADHD children showed a tendency to response and reasoning considered most common at developmental levels inferior to the comparison group. Regarding the use of methylphenidate, there was no significant difference of performance between the subgroups. Results may be indicative that the deficits relate mainly to structuring aspects of thinking, and not to performance. Theoretical and practical implications were discussed.

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The acute effect of methylphenidate in Brazilian male children and adolescents with ADHD: A randomized clinical trial

Abstract: Our results extend the efficacy of MPH on the ADHD core symptoms extensively demonstrated in clinical trials with samples from some developed countries to a sample from a developing country where a diverse culture may modulate the clinical presentation of the disorder.

Cited by 25 publications

References 23 publications

Association between trypotphan hydroxylase 2, performance on a continuance performance test and response to methylphenidate in ADHD participants

Association between trypotphan hydroxylase 2, performance on a continuance performance test and response to methylphenidate in ADHD participants

Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations

Considerations About Psychological Development of Children With ADHD (Attention Deficit Hyperactivity Disorder)

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