Dataset Information

Potential Negative Effects of Dextromethorphan as an Add-On Therapy to Methylphenidate in Children With ADHD.

ABSTRACT: Objectives: Methylphenidate (MPH) is highly effective in controlling the symptoms of attention-deficit/hyperactivity disorder (ADHD), but some children with ADHD either do not respond to, or do not tolerate, treatment. Dextromethorphan (DM) is a neuroprotective agent which has been used in the treatment of neuropsychiatric disorders. This clinical trial had examined the effect of DM on the use of MPH in the children with ADHD. Methods: This randomized double-blind clinical trial had evaluated 44 male outpatients, aged between 6 and 12 years, with a diagnosis of ADHD. The study subjects were randomly assigned into one of the two groups: receiving MPH alone (15-60 mg per day) or MPH plus DM (30-60 mg per day) for 8 weeks. Assessments, comprising the Chinese version of the Child Behavior Checklist (CBCL-C) scale and the Swanson, Nolan and Pelham Questionnaire (SNAP)-IV rating tests conducted by parents and the serum cytokines measured by microarray and enzyme-linked immunosorband assay (ELISA), were compared between groups at baseline and at 8 weeks after the medication was started. Results: There were a significant decrease at the mean scores of both CBCL-C and SNAP-IV scales after 8 weeks of treatment, but no significant differences between MPH and MPH+DM groups. Compared with the MPH-only group, the mean scores of some psychometric parameters reported on the CBCL-C and SNAP-IV scales regarding time effects as well as the attention problems on the CBCL-C scale regarding group effect were significantly higher in the DM+MPH group. Although there were no significant differences in the levels of various serum cytokines between groups, the subjects in the DM-MPH group had relatively fewer and lower levels of adverse effects. Significant interactions were found between the withdrawn/depression item reported on the CBCL-C scale and tumor necrosis factor ? (?TNF-?) (p = 0.027), as well as between thought problems item on the CBCL-C and TNF-? (p = 0.028) in subjects who had received DM+MPH treatment. Conclusion: Following the trial, DM+MPH was not superior to MPH alone for the treatment of children with ADHD, yet DM may potentially have negative effects on ADHD symptoms when combined with MPH. Clinical Trial Registration: Clinicaltrials.gov, trial number: NCT01787136.

SUBMITTER: Chuang WC

PROVIDER: S-EPMC6620613 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Potential Negative Effects of Dextromethorphan as an Add-On Therapy to Methylphenidate in Children With ADHD.

Chuang Wei-Chen WC Yeh Chin-Bin CB Wang Sheng-Chiang SC Pan Pei-Yin PY Shyu Jia-Fwu JF Liu Yia-Ping YP Gau Susan Shur-Fen SS Lu Ru-Band RB

Frontiers in psychiatry 20190626

<b>Objectives:</b> Methylphenidate (MPH) is highly effective in controlling the symptoms of attention-deficit/hyperactivity disorder (ADHD), but some children with ADHD either do not respond to, or do not tolerate, treatment. Dextromethorphan (DM) is a neuroprotective agent which has been used in the treatment of neuropsychiatric disorders. This clinical trial had examined the effect of DM on the use of MPH in the children with ADHD. <b>Methods:</b> This randomized double-blind clinical trial ha ...[more]

PMID: 31333511

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Project description:HIGHLIGHTS Both spatial and temporal analyses of the Center of Pressure demonstrate that children with ADHD have poorer postural control than typically developing sex-, age-, and IQ-matched children.Poor sensory integration in postural control could partially explained the deficits in postural stability in children with ADHD.MPH treatment improves postural performance in both spatial and temporal domains in children with ADHD.MPH improves postural control specifically when visual and proprioceptive inputs are misleading.Such improvement could be due to MPH effects on neurons, facilitating cerebellar processing of postural control. The aim of this study was to examine postural control in children with ADHD and explore the effect of methylphenidate (MPH), using spatial and temporal analyses of the center of pressure (CoP). Thirty-eight children with ADHD (mean age 9.82 ± 0.37 years) and 38 sex- age- and IQ-matched children with typically development were examined. Postural stability was evaluated using the Multitest Equilibre machine (Framiral®) at inclusion and after 1 month of MPH in children with ADHD. Postural stability was assessed by recording under several conditions: with eyes open and fixed on a target, with eyes closed and with vision perturbed by optokinetic stimulation, on stable and unstable platforms. At inclusion, we observed poor spatial and temporal postural stability in children with ADHD. The spectral power index was higher in children with ADHD than in controls. Canceling time was shorter at low and medium frequencies of oscillation and longer at higher frequencies in children with ADHD. After 1 month of MPH, the surface area and mean velocity of the CoP decreased significantly under the most complex conditions (unstable platform in the absence of proprioceptive and visual inputs). The spectral power index decreased significantly after MPH while the canceling time did not change. Poor postural control in children with ADHD supports the hypothesis of cerebellar dysfunction in this disorder. Postural control could be improved by a more efficient processing of sensory inputs (a high-level process), as suggested by the decrease in spectral power index after MPH without changes in the canceling time (a low-level process).

Project description:ObjectiveSleep problems is the most common side effect of methylphenidate (MPH) treatment in ADHD youth and carry potential to negatively impact long-term self-regulatory functioning. This study aimed to examine whether applying machine learning approaches to pre-treatment demographic, clinical questionnaire, environmental, neuropsychological, genetic, and neuroimaging features can predict sleep side effects following MPH administration.MethodThe present study included 83 ADHD subjects as a training dataset. The participants were enrolled in an 8-week, open-label trial of MPH. The Barkley Stimulant Side Effects Rating Scale was used to determine the presence/absence of sleep problems at the 2nd week of treatment. Prediction of sleep side effects were performed with step-wise addition of variables measured at baseline: demographics (age, gender, IQ, height/weight) and clinical variables (ADHD Rating Scale-IV (ADHD-RS) and Disruptive Behavior Disorder rating scale) at stage 1, neuropsychological test (continuous performance test (CPT), Stroop color word test) and genetic/environmental variables (dopamine and norepinephrine receptor gene (DAT1, DRD4, ADRA2A, and SLC6A2) polymorphisms, blood lead, and urine cotinine level) at stage 2, and structural connectivities of frontostriatal circuits at stage 3. Three different machine learning algorithms ((Logistic Ridge Regression (LR), support vector machine (SVM), J48) were used for data analysis. Robustness of classifier model was validated in the independent dataset of 36 ADHD subjects.ResultsClassification accuracy of LR was 95.5% (area under receiver operating characteristic curve (AUC) 0.99), followed by SVM (91.0%, AUC 0.85) and J48 (90.0%, AUC 0.87) at stage 3 for predicting sleep problems. The inattention symptoms of ADHD-RS, CPT response time variability, the DAT1, ADRA2A DraI, and SLC6A2 A-3081T polymorphisms, and the structural connectivities between frontal and striatal brain regions were identified as the most differentiating subset of features. Validation analysis achieved accuracy of 86.1% (AUC 0.92) at stage 3 with J48.ConclusionsOur results provide preliminary support to the combination of multimodal classifier, in particular, neuroimaging features, as an informative method that can assist in predicting MPH side effects in ADHD.

Dataset Information

Potential Negative Effects of Dextromethorphan as an Add-On Therapy to Methylphenidate in Children With ADHD.

Publications

Potential Negative Effects of Dextromethorphan as an Add-On Therapy to Methylphenidate in Children With ADHD.

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