Psychomotor functioning and alertness with guanfacine extended release in subjects with
Scott H Kollins1, Frank A López, Bradley D Vince
1Duke ADHD Program, Duke University Medical Center, Durham, North Carolina 27705, USA. kolli001@mc.duke.edu
Objectives:
To determine whether treatment with guanfacine extended release (GXR) in subjects with attention-deficit/hyperactivity disorder (ADHD) disrupted psychomotor functioning and alertness, or impacted daytime sleepiness.
Method:
This was a randomized, double-blind, placebo-controlled, multicenter, phase 2, dose-optimization, noninferiority, laboratory classroom study of GXR (1, 2, and 3 mg/day) in 182 subjects aged 6 to 17 years with ADHD. Psychomotor functioning and alertness were assessed through several measures, including the Choice Reaction Time (CRT) test from the Cambridge Neuropsychological Test Automated Battery. Sedative effects were examined via spontaneously reported adverse events of sedation, somnolence, and hypersomnia as well as fatigue and lethargy, and with two validated subject- and observer-rated sleepiness scales. Standard efficacy measures for ADHD also were included. Cardiovascular and laboratory parameters were assessed.
Results:
There were no significant differences between the GXR and placebo groups on measures of psychomotor functioning or alertness from the CRT at endpoint (least-square mean difference: 2.5 [95% confidence interval (CI): -22.9, 28.0], p = 0.8 for CRT; 2.5 [95% CI: -21.5, 26.4], p = 0.84 for correct responses; 15.5 [95% CI: -45.1, 14.1], p = 0.30 for movement time; and -8.2 [95% CI: -54.1, 37.6] p = 0.72 for total time). Most sedative adverse events were mild to moderate, occurred during dose titration, decreased with dose maintenance, and resolved during the study period. One subject in the GXR group discontinued due to fatigue and somnolence. GXR was not associated with increased daytime sleepiness. GXR treatment was associated with significant improvement in ADHD symptoms (6.3 [95% CI: 2.7, 9.8], p = 0.001 for ADHD Rating Scale IV total scores at endpoint).
Conclusions:
At doses that resulted in significant improvement in ADHD symptoms, impairment on cognitive tasks was not observed. Daytime sleepiness did not differ with GXR compared with placebo. Results suggest that the beneficial effects of GXR on ADHD symptoms are independent of sedation.
More Related Videos
Related Concept Videos
01:30Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings.
01:24Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of its...
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
01:29Anxiolytic Drugs: Benzodiazepines and Buspirone
01:23Antidepressant Drugs: MAOIs and Other Agents
01:23Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...