Atomoxetine, a Novel Treatment for Attention‐Deficit—Hyperactivity Disorder

Abstract

Atomoxetine is the first nonstimulant drug approved by the United States Food and Drug Administration (FDA) for the treatment of attention-deficit-hyperactivity disorder (ADHD), and the only agent approved by the FDA for the treatment of ADHD in adults. Atomoxetine is a norepinephrine transport inhibitor that acts almost exclusively on the noradrenergic pathway. Its mechanism of action in the control and maintenance of ADHD symptoms is thought to be through the highly specific presynaptic inhibition of norepinephrine. Clinical trials to evaluate the short-term effects of atomoxetine in children and adults have shown that atomoxetine is effective in maintaining control of ADHD. Likewise, long-term trials have determined that atomoxetine is effective in preventing relapse of ADHD symptoms without an increase in adverse effects. A comparative trial of atomoxetine with methylphenidate in school-aged children indicated similar safety and efficacy without the abuse liability associated with some psychostimulants. The most commonly reported adverse effects in children and adolescents are dyspepsia, nausea, vomiting, decreased appetite, and weight loss. The rates of adverse events in the trials were similar for both the once- and twice-daily dosing regimens. The discontinuation rate was 3.5% in patients treated with atomoxetine versus 1.4% for placebo and appeared to be dose dependent, wit a higher percentage of discontinuation at dosages greater than 1.5 mg/kg/day. In clinical trials involving adults, the emergence of clinically significant or intolerable adverse events was low. The most common adverse events in adults were dry mouth, insomnia, nausea, decreased appetite, constipation, urinary retention or difficulties with micturition, erectile disturbance, dysmenorrhea, dizziness, and decreased libido. Sexual dysfunction occurred in approximately 2% of patients treated with atomoxetine. Atomoxetine should be used with caution in patients who have hypertension or any significant cardiovascular disorder. Overall, atomoxetine therapy in patient with ADHD appears to be effective in controlling symptoms and maintaining remission, with the advantages being comparable efficacy with that of methylphenidate, a favorable safety profile, and non-controlled substance status. Additional long-term studies are needed to determine its continued efficacy for those who require lifelong treatment, and comparative trials against other stimulant and nonstimulant agents.

Norepinephrine Transporter Blockade can Normalize the Prepulse Inhibition Deficits Found in Dopamine Transporter Knockout Mice

“…Nonetheless, it is interesting to note that selective serotonin reuptake inhibitors (SSRIs) are reported to be ineffective in ADHD (Findling, 1996), even though fluoxetine appears to reduce hyperactivity in DAT KO mice (Gainetdinov et al, 1999). In the present experiments, we found that the same class of drugs, selective noradrenaline reuptake inhibitors (NRIs), that has been recently shown to effectively treat ADHD symptoms (for a review, see Christman et al, 2004) can also normalize PPI function in DAT KO mice. Similarly, but in contrast to some previous observations (Gainetdinov et al, 1999), we have found that nisoxetine, an NRI, can reduce hyperactivity in DAT KO mice, while citalopram, an SSRI, does not (Fukushima and Sora, unpublished data).…”

Health Care Costs of Adults Treated for Attention-Deficit/Hyperactivity Disorder Who Received Alternative Drug Therapies

“…15 Both stimulant and nonstimulant treatments have been shown to be effective in improving ADHD symptoms. 17,19 Stimulant therapy led to improvement in 65% to 75% versus 5% to 30% of patients randomized to placebo. 19 Nonstimulant therapy has also been shown to improve symptoms assessed with the ADHD rating scales.…”

“…6,13,14 Common medications used for the treatment of ADHD in adults arestimulants (e.g., methylphenidate [MPH], mixed amphetamine salts [MAS], dextroamphetamine) or nonstimulants (e.g., atomoxetine). 4,8,[15][16][17] In the past, treatment options usually included either short-or intermediate-acting stimulants and antidepressants. 18 Recently,s timulant products have entered the marketplace in extended-release formulations; the first methylphenidate product that lasts 12 hours with once-daily dosing is osmotic release oral system (OROS)-MPH, and the once-daily amphetamine preparation is MAS-XR.…”

“…19 Nonstimulant therapy has also been shown to improve symptoms assessed with the ADHD rating scales. 17 Quantifying costs related to ADHD and to alternative therapies is important in order to understand the economic impact of the condition and provide abasis for the development of programs and policies to assist patients suffering from this disability.T he objective of this article is to comparer iskadjusted medical and total health carecosts of adults diagnosed with ADHD initiated on extended-release methylphenidate (OROS-MPH, Concerta), mixed amphetamine salts extended release (MAS-XR, Adderall XR), or atomoxetine (Strattera) from the perspective of alarge self-insured employer.…”

Animal Models of Attention-Deficit/Hyperactivity Disorder

“…Both psychostimulant drugs such as methylphenidate and D-amphetamine and non-psychostimulant medications such as atomoxetine are used as current pharmacotherapy for AD/HD. 2,3) To date, although various clinical studies such as molecular genetic studies and neuroimaging analyses have been reported, the etiology of AD/HD has yet to be revealed. Animal models can be useful to facilitate our understanding of this disorder because they are helpful in studying the behavioral consequences.…”