Long-term outcomes of stimulant medication in attention-deficit hyperactivity disorder
Western Clinical School, Nepean Campus, University of Sydney, Australia. Expert Review of Neurotherapeutics
(Impact Factor: 2.78).
05/2006; 6(4):551-61. DOI: 10.1586/14737188.8.131.521
The rate of prescribing of stimulant medication for the treatment of attention-deficit hyperactivity disorder (ADHD) has been progressively increasing in countries such as the USA and Australia. In the short term, stimulant medication is effective in reducing the symptoms of ADHD and appears well tolerated with relatively minor side effects. In the long term, much of the benefit of stimulant medication disappears after medication is ceased. Studies have demonstrated only marginal improvements in adult outcomes following a period of treatment in childhood. This may be owing to the beneficial effects being masked by the variability of the condition, the developmental changes in symptomatology that happen with maturation and the substantial influence of social and environmental factors. Stimulant medication may give some protection against later substance abuse. Stimulant medication may slightly elevate the blood pressure and possibly increase susceptibility to seizures and to tics and Tourette syndrome. Starting treatment with stimulant medication is usually associated with weight loss and a transient slowing of the height velocity, although it is believed that most children catch up during puberty. No studies were found that listed strokes or heart attacks as potential or actual complications, although one individual from a group of normal controls died suddenly of cardiac arrest in adolescence. It would appear that the medical complications associated with amphetamine addiction are not relevant to the therapeutic use of stimulant medication in the treatment of ADHD, although there is limited information on extended periods of treatment lasting 10 years or more.
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ABSTRACT: Roles of age and withdrawal were explored in mechanisms underlying the action of amphetamine (Amph), by monitoring the serotonergic and GABAergic expression in key brain regions of the rat. Postnatal 21 and 60 day-old male rats were intraperitoneally injected with D-Amph, 5 mg/kg, or saline, three times daily for 14 days and then withdrawn from Amph for 0 or 14 days; these animals received single injections on day 15 (W0d) or day 29 (W14d). Following Amph injections, though both age groups exhibited hyperlocomotion, stereotypy and behavioral sensitization, the juvenile showed 100-300% longer latencies to reach and 30%-42% shorter duration of maximal behavioral scores than the adult from day 2-29. Immunocytochemical analysis revealed down-regulation of 42-76% in 5-hydroxytryptamine (HT) immunoreactive processes in motor and somatosensory cortices, and hippocampus of both ages after Amph exposure at W0d. At W14d, the 5-HT resembled saline-control in the Amph-treated juvenile, whereas remained weakened in the adult. By contrast, densities of GAD67 (glutamic acid decarboxylase)-boutons were up-regulated by 35-545% in the neocortical areas, nucleus accumbens, caudate-putamen and hippocampus of all Amph-administered rats. After 14 days withdrawal, the juvenile recovered the decreased 5-HT fibers, but not the increased GABAergic, indicating unique roles of the two systems in response to Amph.
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ABSTRACT: The ability to be aware of and to interact with the external environment is a basic evolutionary requirement of all higher
organisms requiring intact alertness. Hypersomnia and excessive daytime sleepiness (EDS) relate to the inability to maintain
an alert state during the major waking periods of the day. Up until recently, somnolence arising due to sleep pathology was
misunderstood as a sign of laziness or even malingering by many medical practitioners and society-at-large. The discovery
of the orexin/hypocretin receptor system as a key mediator in abnormal daytime sleepiness as well as growing interest in the
daytime cognitive impact of common sleep disorders have played important roles in improving scientific and public awareness
of hypersomnia as a clinical entity. Hypersomnia, EDS and fatigue are among the most common manifestations of sleep disorders
affecting quality of life (QOL) and productivity. In an increasingly interconnected global economy where workload and productivity
have shifted towards cognitive as opposed to physical labour, research is now focusing more than ever on the impact of disorders
causing somnolence during desired wake time. Similarly, scholastic/academic motivation and performance deficits are being
noted in children and adolescents, in part due to the increased 24/7 availability of technology and entertainment options,
usually at the expense of sufficient sleep. Other important implications of somnolence include the direct and indirect consequences
of transport and occupational accidents, as well as disruption of family and social relationships. Clinical conditions causing
this condition include obstructive sleep apnea (OSA), narcolepsy, idiopathic hypersomnia (IH), circadian disturbances and
most commonly, self-imposed insufficient sleep syndrome. In conditions such as insomnia, restless legs syndrome (RLS) and
periodic limb movements in sleep (PLMS), the association with frank daytime somnolence is more controversial although patients
do complain of impaired daytime cognitive function. As the ‘baby-boom’ generation approaches old age, senescence-related deterioration
of sleep quality and quantity is increasingly recognized as an important factor impacting QOL by affecting memory, cognitive
function and vitality in activities of daily living (ADLs) including driving. Somnolence can be a serious and even life-threatening
impairment. Often there is a gap between the subjective complaints of patients regarding the impact of hypersomnia/EDS on
QOL and the ability to reliably measure this dysfunction. An important area of current research involves clarifying the nosology
of daytime EDS symptoms, ranging from somnolence to fatigue or neurocognitive impairment. Improvements in diagnostic instruments
assessing daytime function and ergonomic activities in relation to both healthy and pathological sleep processes will aid
in better delineating these subjective and objective parameters.
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