Atomoxetine

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. 

Atomoxetine is rapidly absorbed after oral administration, is highly protein bound, and reaches peak plasma concentrations in 1-2 hours (Farid et al. 1985). It is primarily metabolized by the CYP 2D6 isoenzyme, and its half-life differs between extensive 2D6 metab-olizers and poor 2D6 metabolizers (5.2 hours and 21.6 hours, respectively) (Farid et al. 1985). 

Atomoxetine is contraindicated in patients with narrow-angle glaucoma or in combination with an MAOI. 

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

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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... 

The proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

Atomoxetine is the most recent addition to the ADHD armamentarium in both children and adults. In clinical studies, atomoxetine has demonstrated superior efficacy over placebo and equivalent efficacy when compared with a suboptimal immediate-release methylphenidate dose.17 20 However, it is not clear whether atomoxetine is superior to typical methylphenidate doses or other stimulant formulations. Atomoxetine may be used as a second- or third-line medication for ADHD. 

Atomoxetine is similar to extended-acting stimulants in that it can be given once daily in many patients. Atomoxetine appears to lack any abuse potential and is not a controlled substance.22 One big disadvantage of atomoxetine is cost compared with other ADHD medications (Table 39-4). 

Due to the high cost and lack of long-term efficacy and comparison studies with stimulants, atomoxetine should be... 

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]. 

Arginine vasopressin (AVP), 281 Aromatase, 272 Arousal, 133-134 Atomoxetine, 425 Atropine, 308, 399-300 Attention, 117, 125, 127, 130-134, 137 Attentional performance, 146, 160-161 Attention deficit hyperactive disorder (ADHD), 117-118... 

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. 

Monoamine oxidase inhibitors Paroxetine Protriptyline Sertraline Venlafaxine Stimulants Atomoxetine Dextroamphetamine Methylphenidate Modaflnil Pemoline... 

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. 

However, these side effects can be experienced with reboxetine or atomoxetine. Although they are seldom severe, one may need to take steps to remedy the side effects. The first step is to use the smallest effective dose. When this fails, using a second medication such as a benzodiazepine to counteract sleep difficulties or anxiety can be tried. However, without compelling reasons to stay with one of these medications, the best remedy is often to change to a different antidepressant. 

Q33 Patients receiving atomoxetine therapy should be advised ... 

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. 

Concomitant use In children up to 70 kg body weight administered strong CYP2D6 inhibitors, initiate atomoxetine at 0.5 mg/kg/day and only increase to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well-tolerated. 

Discontinuation Atomoxetine can be discontinued without being tapered. 

Pharmacology Atomoxetine is a selective norepinephrine reuptake inhibitor. The precise mechanism by which it produces its therapeutic effects in ADHD is unknown, but it is thought to be related to selective inhibition of the presynaptic norepinephrine transporter, as determined in ex vivo uptake and neurotransmitter depletion studies. Pharmacokinetics ... 

Absorption/Distribution - Atomoxetine is well absorbed after oral administration and is minimally affected by food. It is rapidly absorbed after oral administration, with absolute bioavailability of about 63% in extensive metabolizers (EMs) and 94% in poor metabolizers (PMs). Maximal plasma concentrations (Cmax) reached approximately 1 to 2 hours after dosing. At... 

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