Strattera®

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. 

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. 

Atomoxetine (Strattera) Galantamine (Razadyne) Lisdexamfetamine (Vyvanse)... 

Atomoxetine (Strattera) [ADHD/Selective Norepinephrine Reuptake Inhioiter] WARNING Severe liver injury may rarely occur D/C w/ jaundice or TLFT, T frequency of suicidal thoughts Uses ADHD Action Selective norepinephrine reuptake inhibitor Dose Adults Children >70 kg. 40 mg X 3 d, T to 80-100 mg -s- daily-bid Feds <70 kg. 0.5 mg/kg x 3 d, then T 1.2 mg/kg daily or bid (max 1.4 mg/kg or 100 mg) Caution [C, /-] Contra ... 

Children and adolescents taking atomoxetine should be monitored for the appearance or worsening of aggressive or hostile behavior because these symptoms were noted more frequently in children and adolescents taking atomoxetine than in those taking placebo in clinical trials (Strattera 2005). 

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. 

Strattera (package insert). Indianapolis, IN, Eli Lilly and Co, 2005 Swanson JM, Volkow ND Pharmacokinetic and pharmacodynamic properties of stimulants implications for the design of new treatments for ADHD. Behav Brain Res 130 73-78, 2002 Swanson J, Gupta S, Lam A, et al Development of a new once-daily formulation of methylphenidate for the treatment of attention-deficit/hyperac-tivity disorder proof of concept and proof of product studies. Arch Gen Psychiatry 60 204-211, 2003... 

This chapter will focus on the drugs most commonly and specifically prescribed to children stimulants such as Ritalin, Concerta, Dexedrine, Adderall, and Strattera. A list can be found in the appendix. 

The stimulant drugs, including all methylphenidate and amphetamine products, produce a wide array of adverse effects on the brain and mind as well as the overall body. Strattera, marketed by Eli Lilly as a nonstimulant, shares most of these adverse effects. Table 11.1 summarizes the adverse drug reaction data from eight controlled clinic trials. Table 11.2... 

Eli Lilly promoted and continues to promote Strattera as the nonstimulant drug to treat ADHD (Eli Lilly and Company, 2006). While the company maintains this position, the drug is nonetheless listed under Central Nervous System Stimulants in the Physicians Desk Reference (2007, p. 208). Lilly s extremely shrewd marketing ploy of promoting Strattera as a nonstimulant is meant to allay the concerns of parents and doctors about their children taking stimulants for ADHD. 

It is true that Strattera has not been demonstrated to cause dependence and abuse like Ritalin, Adderall, and the other stimulant drugs used to treat ADHD and therefore has not been placed in Schedule II by the DEA. But Strattera is a highly stimulating drug. According to the label for Strattera, as found in the Physicians Desk Reference (2007, p. 1817, Table 1), in the clinical trials used for FDA approval, irritability was reported in 8% of subjects, crying in 2%, and mood swings in 2%. 

In overdose, like any stimulant, Strattera can cause severe seizures (Sawant et al., 2004). 

Strattera is the one ADHD treatment that has received a black-box warning concerning increased suicidality. After a review and analysis of 13 clinical trials conducted with children, all but one for the treatment of ADHD, the FDA (2005c) identified an increased risk of suicidal thinking for Strattera. The bold black-box warning included in the label can be found in the 2007 Physicians Desk Reference ... 

Suicidal ideation in Child and Adolescents—STRATTERA (atomoxetine) increased the risk of suicidal ideation in short-term studies in children or adolescents with Attention-Deficit Hyperactivity Disorder (ADHD). Anyone considering the use of STRATTERA in a child or adolescent must balance this risk with the clinical needs. Patients who are started on therapy should be monitored closely for suicidality (suicidal thinking and behavior), clinical worsening, or unusual changes in behavior. 

Suicidality has been identified as a safety issue for STRATTERA (ato-moxetine), and this information is clearly conveyed in current labeling. A causal association between other drug therapies of ADHD and suicidality cannot be ruled out on the basis of this review. Further evaluation of this issue is recommended. (FDA, 2006b)... 

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). 

With the exception of Strattera, all of the stimulants approved for the treatment of attention-deficit/hyperactivity disorder cause potentially... 

Eli Lilly and Company. (2006). Strattera. Retrieved June 8, 2007, from http //www.strat tera.com... 

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