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Stimulant therapy in children with attention-deficit/hyperactivity disorder and concomitant long QT syndrome: A safe combination?

ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is prevalent in about 11% of children in the United States. As such, ADHD is expected to be present in patients with long QT syndrome (LQTS), a rare, potentially lethal but highly treatable cardiac channelopathy. ADHD-directed stimulant therapy is relatively contraindicated in patients with LQTS because of concern for LQTS-triggered events.The purpose of this study was to evaluate the ADHD-directed treatment, outcome, and frequency of LQTS-triggered events in patients with LQTS and concomitant ADHD.A retrospective electronic medical record review of 357 pediatric patients with LQTS evaluated between 1999 and 2014 was performed to determine the prevalence of concomitant ADHD and the incidence of LQTS-triggered events in patients with LQTS, with or without concomitant ADHD.Overall, 28 patients (8%) were diagnosed with LQTS concomitant ADHD. There were no phenotypic differences between patients with LQTS and ADHD, and LQTS alone. ADHD-directed stimulant therapy was stopped or advised against in 19 patients (68%) at the time of first evaluation or after diagnosis. None of the 15 stimulant-treated patients experienced LQTS-triggered events in a combined 56 person-years of treatment. Perhaps paradoxically, there was a statistically lower LQTS-triggered event rate in the stimulant-treated ADHD group compared to the LQTS alone cohort.Among patients with mild- to moderate-risk LQTS, we found a prevalence of ADHD similar to that in the general population, which can be treated effectively and safely with stimulant therapy. Physicians should find reassurance in the low adverse event rate and should weigh the potential effects of suboptimal treatment of ADHD with the theoretical proarrhythmic risk from stimulant medications.

SUBMITTER: Rohatgi RK

PROVIDER: S-EPMC5084529 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Stimulant therapy in children with attention-deficit/hyperactivity disorder and concomitant long QT syndrome: A safe combination?

Rohatgi Ram K RK Bos J Martijn JM Ackerman Michael J MJ

Heart rhythm 20150505 8

<h4>Background</h4>Attention-deficit/hyperactivity disorder (ADHD) is prevalent in about 11% of children in the United States. As such, ADHD is expected to be present in patients with long QT syndrome (LQTS), a rare, potentially lethal but highly treatable cardiac channelopathy. ADHD-directed stimulant therapy is relatively contraindicated in patients with LQTS because of concern for LQTS-triggered events.<h4>Objective</h4>The purpose of this study was to evaluate the ADHD-directed treatment, ou ...[more]

PMID: 25956966

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Project description:Intra-subject variability (ISV) is the most consistent behavioral deficit in Attention Deficit Hyperactivity Disorder (ADHD). ISV may be associated with networks involved in sustaining task control (cingulo-opercular network: CON) and self-reflective lapses of attention (default mode network: DMN). The current study examined whether connectivity supporting attentional control is atypical in children with ADHD. Group differences in full-brain connection strength and brain-behavior associations with attentional control measures were examined for the late-developing CON and DMN in 50 children with ADHD and 50 typically-developing (TD) controls (ages 8-12 years). Children with ADHD had hyper-connectivity both within the CON and within the DMN. Full-brain behavioral associations were found for a number of between-network connections. Across both groups, more anti-correlation between DMN and occipital cortex supported better attentional control. However, in the TD group, this brain-behavior association was stronger and occurred for a more extensive set of DMN-occipital connections. Differential support for attentional control between the two groups occurred with a number of CON-DMN connections. For all CON-DMN connections identified, increased between-network anti-correlation was associated with better attentional control for the ADHD group, but worse attentional control in the TD group. A number of between-network connections with the medial frontal cortex, in particular, showed this relationship. Follow-up analyses revealed that these associations were specific to attentional control and were not due to individual differences in working memory, IQ, motor control, age, or scan motion. While CON-DMN anti-correlation is associated with improved attention in ADHD, other circuitry supports improved attention in TD children. Greater CON-DMN anti-correlation supported better attentional control in children with ADHD, but worse attentional control in TD children. On the other hand, greater DMN-occipital anti-correlation supported better attentional control in TD children.

Project description:ObjectiveBecause models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses. This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH) with guanfacine (GUAN), an α2A receptor agonist, would be clinically superior to either monotherapy and would have equal tolerability.MethodAn 8-week, double-blind, 3-arm, comparative trial randomized 7- to 14-year-olds with DSM-IV ADHD to GUAN (1-3 mg/day), DMPH (5-20 mg/day), or a combination (COMB) with fixed-flexible dosing. Outcome measures were the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Data on adverse events and safety measures were obtained.ResultsA total of 207 participants were randomized and received drug. Analyses showed significant treatment group main effects for ADHD-RS-IV ADHD total (p = .0001) and inattentive symptoms (p = .0001). COMB demonstrated small but consistently greater reductions in ADHD-RS-IV Inattentive subscale scores versus monotherapies (DMPH: p = .05; f(2) = .02; and GUAN: p = .02; f(2) = .02), and was associated with a greater positive response rate by CGI-I (p = .01). No serious cardiovascular events occurred. Sedation, somnolence, lethargy, and fatigue were greater in both guanfacine groups. All treatments were well tolerated.ConclusionCOMB showed consistent evidence of clinical benefits over monotherapies, possibly reflecting advantages of greater combined dopaminergic and α2A agonism. Adverse events were generally mild to moderate, and COMB treatment showed no differences in safety or tolerability.Clinical trial registration informationSingle Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); http://clinicaltrials.gov/; NCT00429273.

Dataset Information

Stimulant therapy in children with attention-deficit/hyperactivity disorder and concomitant long QT syndrome: A safe combination?

Publications

Stimulant therapy in children with attention-deficit/hyperactivity disorder and concomitant long QT syndrome: A safe combination?

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