Effects of long-term atomoxetine treatment for young children with attention-deficit/hyperactivity disorder
ABSTRACT The purpose of this 13-study (seven double-blind/placebo-controlled, six open-label) meta-analysis is to determine the effectiveness and tolerability of long-term atomoxetine treatment among young children with attention-deficit/hyperactivity disorder (ADHD).
Data were pooled from 6- and 7-year-olds (N = 272) who met DSM-IV criteria for ADHD, received atomoxetine treatment, and were enrolled in clinical trials of > or =2 years. Of these, 97 subjects reached the 24-month time point, providing data for long-term trend analysis of safety and effectiveness.
Effectiveness for most subjects was maintained over long-term treatment, as demonstrated by total scores and total T scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version, investigator administered and scored. During the 2-year period, 25.7% discontinued because of lack of effectiveness, but adverse events were clinically minor and transient, and only 4.0% of children discontinued because of an adverse event. Notable effects on growth were seen during early phases of the study, with attenuation occurring by the 2-year time point. Statistically significant increases in pulse and blood pressure and decreases in cardiac PR interval were seen, but no changes were deemed both statistically significant and clinically meaningful among any vital signs, electrocardiographic measures, or laboratory tests.
Long-term atomoxetine treatment appears generally well tolerated and effective in the treatment of young children with ADHD.
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- "Two additional meta-analyses assessed reported the effect of longterm use of ATX on height and weight. The first showed a decrease in weight (average 2.5 kg) and in height (average 2.7 cm) after 2 years of treatment with ATX in 6–7-year-old children in relation to baseline percentiles (Kratochvil et al. 2006). The second metaanalysis reported a less evident effect on weight and height, 0.87 kg and 0.44 cm, respectively (Spencer et al. 2005). "
ABSTRACT: Abstract Objective: This study was conducted to assess the long-term effect of methylphenidate (MPH) or atomoxetine (ATX) on growth in attention-deficit/hyperactivity disorder (ADHD) drug-naïve children. Design: The study was an observational, post-marketing, fourth phase study. Methods: Data on height and weight were collected at baseline and every 6 months up to 24 months. Results: Both ATX and MPH lead to decreased height gain (assessed by means of z-scores); the effect was significantly higher for ATX than for MPH. At any time, height z-score decrease in the ATX group was higher than the corresponding decrease observed in the MPH group, but the difference was significantly relevant only during the first year of treatment. An increment of average weight was observed both in patients treated with MPH and in those treated with ATX. However, using Tanner's percentile, a subset of patients showed a degree of growth lower than expected. This negative effect was significantly higher for ATX than for MPH. Conclusions: We conclude that ADHD drugs show a negative effect on linear growth in children in middle term. Such effect appears more evident for ATX than for MPH.Journal of child and adolescent psychopharmacology 09/2013; 23(7). DOI:10.1089/cap.2012.0086 · 3.07 Impact Factor
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- "Pharmacological analysis of the effects of amphetamine has indicated that DA neurotransmission plays an important, opposing role in the modulation of impulsive action and impulsive choice (Cole and Robbins 1989; Pattij et al. 2007; van Gaalen et al. 2006a, 2006b, 2009). Atomoxetine is a potent NA reuptake inhibitor with no appreciable affinity for the DA or 5-HT transporter (Bolden-Watson and Richelson 1993), which has been shown to be effective in the treatment of ADHD (Kratochvil et al. 2006; Simpson and Perry 2003; Spencer et al. 2002; Wilens et al. 2006). Although selective inhibition of NA reuptake has been reported to have beneficial effects on impulsive action in the 5-CSRTT (Blondeau and Dellu- Hagedorn 2007; Navarra et al. 2008; Paine et al. 2007; Paterson et al. 2011; Robinson et al. 2008; Sun et al. 2011; Van Gaalen et al. 2006a), its effects on impulsive choice are inconclusive (Robinson et al. 2008; Sun et al. 2011; Van Gaalen et al. 2006b). "
ABSTRACT: High levels of impulsivity are a core symptom of psychiatric disorders such as ADHD, mania, personality disorders and drug addiction. The effectiveness of drugs targeting dopamine (DA), noradrenaline (NA) and/or serotonin (5-HT) in the treatment of impulse control disorders emphasizes the role of monoaminergic neurotransmission in impulsivity. However, impulsive behavior is behaviorally and neurally heterogeneous, and several caveats remain in our understanding of the role of monoamines in impulse control. This study aims to investigate the role of DA, NA and 5-HT in two main behavioral dimensions of impulsivity. The effects of selective DA (GBR12909; 2.5-10 mg/kg), NA (atomoxetine; 0.3-3.0 mg/kg) and 5-HT (citalopram; 0.3-3.0 mg/kg) reuptake inhibitors as well as amphetamine (0.25-1.0 mg/kg) were evaluated on impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task (DRT). In the 5-CSRTT, neuropharmacological challenges were performed under baseline and long intertrial interval (ITI) conditions to enhance impulsive behavior in the task. Amphetamine and GBR12909 increased impulsive action and perseverative responding and decreased accuracy and response latency in the 5-CSRTT. Atomoxetine increased errors of omission and response latency under baseline conditions in the 5-CSRTT. Under a long ITI, atomoxetine also reduced premature and perseverative responding and increased accuracy. Citalopram improved impulse control in the 5-CSRTT. Amphetamine and GBR12909, but not citalopram or atomoxetine, reduced impulsive choice in the DRT. Elevation of DA neurotransmission increases impulsive action and reduces impulsive choice. Increasing NA or 5-HT neurotransmission reduces impulsive action.Psychopharmacology 12/2011; 219(2):313-26. DOI:10.1007/s00213-011-2576-x · 3.99 Impact Factor
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- "Whereas methylphenidate increases DA and NE in the prefrontal cortex as well as DA in the nucleus accumbens and striatum, atomoxetine does not alter DA in the nucleus accumbens or striatum, but works by increasing extracellular NE and DA levels in the prefrontal cortex, by blocking the NE transporter (NET) (Bymaster et al. 2002). Atomoxetine has proved to be efficient in reducing ADHD symptoms (Kratochvil et al., 2006; Wilens et al., 2006b; Adler et al., 2009), is usually well tolerated and in contrast to methylphenidate has little potential as a drug of abuse (Bymaster et al., 2002). The effects of atomoxetine on cognitive task performance have not been widely studied yet, but atomoxetine has been found to improve response inhibition in adults with ADHD (Chamberlain et al., 2007). "
ABSTRACT: Driving is a complex task and is susceptible to inattention and distraction. Moreover, alcohol has a detrimental effect on driving performance, possibly due to alcohol-induced attention deficits. The aim of the present study was to assess the effects of alcohol on simulated driving performance and attention orienting and allocation, as assessed by event-related potentials (ERPs). Thirty-two participants completed two test runs in the Divided Attention Steering Simulator (DASS) with blood alcohol concentrations (BACs) of 0.00%, 0.02%, 0.05%, 0.08% and 0.10%. Sixteen participants performed the second DASS test run with a passive auditory oddball to assess alcohol effects on involuntary attention shifting. Sixteen other participants performed the second DASS test run with an active auditory oddball to assess alcohol effects on dual-task performance and active attention allocation. Dose-dependent impairments were found for reaction times, the number of misses and steering error, even more so in dual-task conditions, especially in the active oddball group. ERP amplitudes to novel irrelevant events were also attenuated in a dose-dependent manner. The P3b amplitude to deviant target stimuli decreased with blood alcohol concentration only in the dual-task condition. It is concluded that alcohol increases distractibility and interference from secondary task stimuli, as well as reduces attentional capacity and dual-task integrality.Journal of Psychopharmacology 03/2010; 24(9):1333-48. DOI:10.1177/0269881109348168 · 2.81 Impact Factor