Treatments atomoxetine

The most common treatment of ADHD is pharmacological. Psychostimulant diugs such as methylpheni-date and amphetamine or atomoxetin, an inhibitor of the noradrenaline transporter can be prescribed. These agents elicit the non-exocytotic release of... 

Gibson AP, Bettinger TL, Patel NC, Crismon ML (2006) Atomoxetine versus stimulants for treatment of attention deficit/hyperactivity disorder. Ann Pharmacother 40 1134-1142... 

Atomoxetine (9), a selective NRI, is the first non-stimulant drug approved for the treatment of ADHD [22]. Interestingly, in a recent 12-week, randomized, double blind, placebo-controlled trial in 30 obese women, atomoxetine demonstrated modest short-term weight loss efficacy relative to placebo [23]. 

Althongh some gronps have used the controversy snrronnding ADHD as a platform to attack the nse of psychiatric medications as a whole, we should not in onr haste to dismiss snch perspectives overlook the fact that these are fair and reasonable qnestions. For that reason, we will try in this chapter to address these questions as we discnss the diagnosis, the long-term conrse, and the treatment of ADHD. The treatment options have recently expanded with the FDA approval of atomoxetine (Strattera), a selective norepinephrine renptake inhibitor that is not a psychostimn-lant, for the treatment of ADHD. 

Atomoxetine (Strattera). Atomoxetine has recently been approved as a treatment for ADHD. Atomoxetine, similar to some of the antidepressants discussed later, is a preferential inhibitor of norepinephrine reuptake. Because nerve terminals in the cerebral cortex have no dopamine reuptake sites, dopamine is taken up at nearby norepinephrine reuptake sites. Consequently, all norepinephrine reuptake inhibitors increase the availability of dopamine in the prefrontal cortex, likely the primary mechanism of atomoxetine action in ADHD. 

First-line pharmacotherapy treatments include methylphenidate, dextroamphetamine, the mixed amphetamine salts (Adderall), and atomoxetine (see Table 8.3). When an early evening dose is indicated (e.g., completion of homework) it is typically at 25-50% of the doses prescribed earlier in the day. 

Starting Treatment in Adults with ADHD. Beginning treatment of an adult is not significantly different from doing so in a child. The stimulants and atomoxetine remain the most effective medications. Methylphenidate, dextroamphetamine, and Adderall appear to be equally effective in group trials, but individuals may respond preferentially to one medication or the other. 

Medications that enhance norepinephrine activity can do so in one of several ways. First, they can block the reuptake of norepinephrine back into the nerve cell once it has been released. This keeps the norepinephrine in the synapse longer and therefore makes it more active. The tricyclic antidepressants (TCAs), duloxetine (Cymbalta), and venlafaxine (Effexor) act in this manner, as does paroxetine (Paxil) at higher doses. Atomoxetine (Strattera), a treatment for ADHD, also works in this way. 

Maintenance treatment There is no evidence available from controlled trials to indicate how long the patient with ADHD should be treated with atomoxetine. However, pharmacological treatment of ADHD may be needed for extended periods. Periodically re-evaluate the long-term usefulness of the drug for the individual patient. 

MAOIs Do not take atomoxetine with an MAOl or within 2 weeks after discontinuing an MAOl. Do not initiate treatment with an MAOl within 2 weeks after discontinuing atomoxetine. With other drugs that affect brain monoamine concentrations, there... 

Children The safety and efficacy of atomoxetine in pediatric patients less than 6 years of age have not been established. The efficacy of atomoxetine beyond 9 weeks and safety of atomoxetine beyond 1 year of treatment have not been systematically evaluated. 

APPROVED TREATMENTS FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER AMPHETAMINE (ADDERALL ), METHYLPHENIDATE (RITALIN ), AND ATOMOXETINE (STRATERRA )... 

As of 2006, there are several branded medications approved for the treatment of ADHD however, there are only three chemicals that make up the primary active ingredients in these drugs the (5)-enantiomer of amphetamine (1), the 2(/ ),2 (7 )-enantiomer of methylphenidate (2), and the (/ )-enantiomer of atomoxetine (3). An older approved ADHD drug, pemoline (Cylert ), was withdrawn from the market in 2005 due to reported... 

Atomoxetine (Straterra , originally tomoxetine or tomoxetin, 3) was first described and synthesized by chemists at Eli Lilly in the late 1970s and was one of the few compounds that was known to display meaningful selectivity for the norepinephrine reuptake transporter (NET) versus the serotonin reuptake transporter (SERT) and the dopamine reuptake transporter (DAT) (Barnett, 1986 Molloy and Schmiegel, 1997). Atomoxetine was one of several structurally related and commercially successful monoamine reuptake inhibitors that were developed by Lilly for the treatment of various psychiatric disorders (Eig. 17.4). Fluoxetine (43) and duloxetine (44) have both gained approval in the United States as Prozac and Cymbalta , respectively, and nisoxetine (45) is widely used as a tool in biology. 

Atomoxetine is not commercially available but is currently undergoing investigational use as treatment for ADHD in children and adults. A recent randomized placebo-controlled trial was conducted in a pediatric outpatient population with ADHD (N = 297), and results suggest that atomoxetine is superior to placebo in reducing ADHD symptoms and in improving social and family functioning (Michelson et ah, 2001). 

Although purely speculative, atomoxetine may have uses in the treatment of depression and/or anxiety, either alone or in combination with other medications. 

Michelson, D., Paries, D., Wernicke, J., Kelsey, D., Kendrick, K., Sallee, RR., Spencer, T. (2001) Atomoxetine in the treatment of children and adolescents with attention deficit / hyperactivity disorder a randomized place to controlled, dose response study. Pediatrics 108 E83. 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

Atomoxetine is a nonstimulant medication approved by the U.S. FDA for the treatment of ADHD in children older than 6 years, ad-... 

Atomoxetine is a selective inhibitor of norepinephrine presynaptic reuptake transporters that has been shown to increase extracellular norepinephrine and dopamine concentrations in the prefrontal cortex in rats (Bymaster et al. 2002), which may account for its clinical efficacy in the treatment of ADHD symptomatology. However, atomoxetine does not appear to affect dopamine levels in the striatum or nucleus accumbens and consequently is not thought to carry the abuse potential associated with stimulant medications. 

Available safety data come from short-term trials of atomoxetine in the treatment of ADHD. Common side effects in studies of atomox-... 

Additionally, current product labeling contains a boxed warning regarding an increased risk of suicidal ideation in children and adolescents. Pooled analyses of 12 short-term atomoxetine trials showed an average risk of suicidal ideation of 0.4% in patients taking atomoxetine, compared with none in patients receiving placebo (Strattera 2005). Patients should be advised of the risks associated with atomoxetine prior to treatment. 

Adderall XR (package insert). Wayne, PA, Shire US Inc, 2004 Angrist B, d Hollosy M, Sanfilipo M, et al Central nervous system stimulants as symptomatic treatments for AIDS-related neuropsychiatric impairment. J Clin Psychophamiacol 12 268—272, 1992 Arnold LE, Lindsay RL, Connors CK, et al A douhle-hlind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention-deficit hyperactivity disorder. I Am Acad Child Adolesc Psychiatry 14 542—554, 2004 Belle DJ, Ernest CS, Sauer JM, et al Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. I Clin Pharmacol 42 1219-1227, 2002... 

Kratochvil CJ, Heiligenstein JH, Dittmann R, et al Atomoxetine and methylphenidate treatment in children with ADHD a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 41 776-784, 2002... 

Michelson D, Allen AJ, Busner J, et al Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder a randomized, placebo-controlled study. Am J Psychiatry 159 1896-1901, 2002... 

U.S. Modafinil in Narcolepsy Multicenter Study Group Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 54 1166-1175, 2000 Wernicke JF, Kratochvil CJ Safety profile of atomoxetine in the treatment of children and adolescents with ADHD. J Clin Psychiatry 63 (suppl 12) 50-55, 2002... 

Atomoxetine is a selective inhibitor of the norepinephrine reuptake transporter. Its actions, therefore, are mediated by potentiation of norepinephrine levels in noradrenergic synapses. It is used in the treatment of attention deficit disorders (see below). Atomoxetine has surprisingly little cardiovascular effect because it has a clonidine-like effect in the central nervous system to decrease sympathetic outflow while at the same time potentiating the effects of norepinephrine in the periphery. However, it may increase blood pressure in some patients. Norepinephrine reuptake is particularly important in the heart, particularly during sympathetic stimulation, and this... 

Strattera (atomoxetine), the supposedly safer nonstimulant treatment for ADHD, turned out to be highly stimulating and is the only ADHD treatment required to carry a black-box warning, with a heading about how it can cause Suicidal Ideation in Children and Adolescents (chapter 11). 

SSRIs, SNRIs, or mirtazapine for treatment-resistant depression (use combinations ot antidepressants with atomoxetine with caution as this may theoretically activate bipolar disorder and suicidal ideation)... 

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