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 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atomoxetine (Strattera(R)) is a selective norepinephrine (noradrenaline) reuptake inhibitor that is not classified as a stimulant, and is indicated for use in patients with attention-deficit hyperactivity disorder (ADHD). Atomoxetine is effective and generally well tolerated. It is significantly more effective than placebo and standard current therapy and does not differ significantly from or is noninferior to immediate-release methylphenidate; however, it is significantly less effective than the extended-release methylphenidate formulation OROS(R) methylphenidate (hereafter referred to as osmotically released methylphenidate) and extended-release mixed amfetamine salts. Atomoxetine can be administered either as a single daily dose or split into two evenly divided doses, has a negligible risk of abuse or misuse, and is not a controlled substance in the US. Atomoxetine is particularly useful for patients at risk of substance abuse, as well as those who have co-morbid anxiety or tics, or who do not wish to take a controlled substance. Thus, atomoxetine is a useful option in the treatment of ADHD in children and adolescents. The mechanism of action of atomoxetine is unclear, but is thought to be related to its selective inhibition of presynaptic norepinephrine reuptake in the prefrontal cortex. Atomoxetine has a high affinity and selectivity for norepinephrine transporters, but little or no affinity for various neurotransmitter receptors. Atomoxetine has a demonstrated ability to selectively inhibit norepinephrine uptake in humans and animals, and studies have shown that it preferentially binds to areas of known high distribution of noradrenergic neurons, such as the fronto-cortical subsystem. Atomoxetine was generally associated with statistically, but not clinically, significant increases in both heart rate and blood pressure in pediatric patients with ADHD. While there was an initial loss in expected height and weight among atomoxetine recipients, this eventually returned to normal in the longer term. Data suggest that atomoxetine is unlikely to have any abuse potential. Atomoxetine appeared less likely than methylphenidate to exacerbate disordered sleep in pediatric patients with ADHD. Atomoxetine is rapidly absorbed, and demonstrates dose-proportional increases in plasma exposure. It undergoes extensive biotransformation, which is affected by poor metabolism by cytochrome P450 (CYP) 2D6 in a small percentage of the population; these patients have greater exposure to and slower elimination of atomoxetine than extensive metabolizers. Patients with hepatic insufficiency show an increase in atomoxetine exposure. CYP2D6 inhibitors, such as paroxetine, are associated with changes in atomoxetine pharmacokinetics similar to those observed among poor CYP2D6 metabolizers. Once- or twice-daily atomoxetine was effective in the short-term treatment of ADHD in children and adolescents, as observed in several well designed placebo-controlled trials. Atomoxetine also demonstrated efficacy in the longer term treatment of these patients. A single morning dose was shown to be effective into the evening, and discontinuation of atomoxetine was not associated with symptom rebound. Atomoxetine efficacy did not appear to differ between children and adolescents. Stimulant-naive patients also responded well to atomoxetine treatment. Atomoxetine did not differ significantly from or was noninferior to immediate-release methylphenidate in children and adolescents with ADHD with regard to efficacy, and was significantly more effective than standard current therapy (any combination of medicines [excluding atomoxetine] and/or behavioral counseling, or no treatment). However, atomoxetine was significantly less effective than osmotically released methylphenidate and extended-release mixed amfetamine salts. The efficacy of atomoxetine did not appear to be affected by the presence of co-morbid disorders, and symptoms of the co-morbid disorders were not affected or were improved by atomoxetine administration. Health-related quality of life (HR-QOL) appeared to be positively affected by atomoxetine in both short- and long-term studies; atomoxetine also improved HR-QOL to a greater extent than standard current therapy. Atomoxetine was generally well tolerated in children and adolescents with ADHD. Common adverse events included headache, abdominal pain, decreased appetite, vomiting, somnolence, and nausea. The majority of adverse events were mild or moderate; there was a very low incidence of serious adverse events. Few patients discontinued atomoxetine treatment because of adverse events. Atomoxetine discontinuation appeared to be well tolerated, with a low incidence of discontinuation-emergent adverse events. Atomoxetine appeared better tolerated among extensive CYP2D6 metabolizers than among poor metabolizers. Slight differences were evident in the adverse event profiles of atomoxetine and stimulants, both immediate- and extended-release. Somnolence appeared more common among atomoxetine recipients and insomnia appeared more common among stimulant recipients. A black-box warning for suicidal ideation has been published in the US prescribing information, based on findings from a meta-analysis showing that atomoxetine is associated with a significantly higher incidence of suicidal ideation than placebo. Rarely, atomoxetine may also be associated with serious liver injury; postmarketing data show that three patients have had liver-related adverse events deemed probably related to atomoxetine treatment. Treatment algorithms involving the initial use of atomoxetine appear cost effective versus algorithms involving initial methylphenidate (immediate- or extended-release), dexamfetamine, tricyclic antidepressants, or no treatment in stimulant-naive, -failed, and -contraindicated children and adolescents with ADHD. The incremental cost per quality-adjusted life-year is below commonly accepted cost-effectiveness thresholds, as shown in several Markov model analyses conducted from the perspective of various European countries, with a time horizon of 1 year.
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PMID:Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. 1944 48

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.
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PMID:Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. 2375 86

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder in children and adults characterized by a persistent pattern of impulsiveness, inattention and hyperactivity. It affects about 3-10% of children and 2-5% of adolescents and adults and occurs about four times more commonly in boys than girls. The cause of ADHD is unknown, but it has strong genetic and environment components. The first-line treatment options for ADHD include behavioral therapy, pharmacotherapy with stimulants or both. Methylphenidate and amphetamine salts are the stimulant drugs of choice for ADHD treatment. Amphetamines act by increasing presynaptic release of dopamine and other biogenic amines in the brain. Methylphenidate inhibits the reuptake of dopamine and norepinephrine and therefore its pharmacology is identical to that of amphetamines. Lisdex-amfetamine is a prodrug of dextroamphetamine with low feasibility for abuse. Atomoxetine, a selective norepinephrine reuptake inhibitor, is an alternative, non-stimulant drug for ADHD but it is less efficacious than stimulants. Stimulants are generally safe but are associated with adverse effects including headache, insomnia, anorexia and weight loss. There is increased awareness about serious cardiovascular and psychiatric adverse events with ADHD drugs including concern for growth suppression in children. Stimulants have a high potential for abuse and dependence, and should be handled safely to prevent misuse and abuse.
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PMID:Current pharmacotherapy of attention deficit hyperactivity disorder. 2419 Dec 57

Adverse drug reactions are common in drugs used during childhood and adolescence. Atomoxetine, a selective reuptake inhibitor, was introduced as a safe non-stimulant alternative treatment for attention deficit hyperactivity disorder. Described common side effects of atomoxetine include: headache, abdominal pain, decreased appetite, fatigue, nausea, vomiting and dizziness. In our case, we present an adolescent male who developed hypothermia under atomoxetine treatment. To our knowledge, this is the first report of a causal connection between atomoxetine intake and hypothermia. Because hypothermia is a life-threatening condition and can be treated when interfered immediately, clinicians should be aware of this adverse effect of atomoxetine.
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PMID:Atomoxetine Induced Hypothermia: A Case Report. 2773 58