Article: Atomoxetine

Atomoxetine
Systematic (IUPAC) name
(3S)-N-methyl-3-(2-methylphenoxy)-3-phenyl-propan-1-amine
Identifiers
CAS number	82248-59-7
ATC code	N06BA09
PubChem	54841
DrugBank	APRD00614
Chemical data
Formula	C17H21NO·HCl
Mol. weight	291.82 (255.355 without HCl)
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic, via CYP2D6
Half life	5 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	Unscheduled
Routes	Oral (Capsules: 5, 10, 18, 25, 40 and 60 mg)

Atomoxetine is the first non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). It is sold in the form of the hydrochloride salt of atomoxetine. It is manufactured and marketed under the brand name Strattera^® by Eli Lilly and Company. There is currently no generic available within the United States due to patent restrictions; however, a generic is available outside the United States, which is manufactured by Torrent Pharmaceuticals.

Atomoxetine is classified as a norepinephrine reuptake inhibitor, and is approved for use in children, adolescents, and adults. However, its efficacy has not been studied in children under 6 years old. Its advantage over stimulants for the treatment of ADHD is that it has less abuse potential than stimulants, is not scheduled as a controlled substance and has proven in clinical trials to offer 24 hour coverage of symptoms associated with ADHD in adults and children.

Nomenclature

Atomoxetine was originally known as "tomoxetine". However, the US FDA requested the name be changed because, in their opinion, the similarity of "tomoxetine" to "tamoxifen" (a breast cancer drug) could lead to dispensing errors at pharmacies.

Chemistry and Composition

Atomoxetine is designated chemically as (-)-N-Methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydrochloride, and has a molecular mass of 291.82. It has a solubility of 27.8 mg/mL in water. Atomoxetine is a white solid that exists as a granular powder inside the capsule, along with pregelatinized starch and dimethicone. The capsule shells contain gelatin, sodium lauryl sulfate, FD&C Blue No. 2, synthetic yellow iron oxide, titanium dioxide, red iron oxide, edible black ink, and trace amounts of other inactive ingredients.

Side effects

The most common side effect is drowsiness. This can be counteracted in some patients by measures as simple as a cup of coffee, or breathing exercises. While others become exhausted after a short while after taking the pills, and can sleep for up to 10+ hours. Some patients tend to feel lightheaded and/or dizziness as a minor side effect along with the drowsiness. Another common side effect is heartburn. This usually occurs when the medicine is taken without food, as per instruction.

Some studies suggest that Strattera has a tendency to exacerbate existing anxiety disorders, particularly social anxiety and panic attacks. This may be linked to the theory that the production and reuptake of norepinephrine in excess is the cause of such disorders.

A significant minority of adult male patients taking Strattera suffer minor to severe sexual side effects, including erectile dysfunction, retrograde ejaculation, painful orgasm, and the decoupling of orgasm from ejaculation, wherein ejaculation takes place up to ten seconds before or after orgasm.

In September 2005, Strattera was determined to increase risk of suicidal thoughts among children and adolescents; one attempted suicide and five cases of suicidal thoughts were reported out of 1,357 young patients taking Strattera, while none were reported out of a control group of 851 taking placebos. [1], [2]. The FDA has required that black box warnings be placed on all antidepressant medications warning they may result in increased risk of suicidal tendencies in children and adolescents, therefore Strattera bears such a warning.

Two confirmed cases of liver injury have been reported by Eli Lilly and Company out of approximately two million prescriptions written. In both cases upon discontinuation of atomoxetine, patients' liver functions returned to normal.

Potential for abuse

To date, the potential for abuse of Strattera has not been exhaustively researched. The two studies that have been performed suggest that atomoxetine has a low to moderate risk for abuse, since it has a long titration time (meaning that a it may have no effect on the user unless they've been taking it regularly for days) and does not produce strong stimulating effects like most other ADHD medications (which are usually dopamine reuptake inhibitors). Monkeys will not self-administer atomoxetine at the doses tested (Gasior et al, Neuropharm 30:758, 2005; Wee & Woolverton, Drug Alcohol Depend 75:271, 2004). However, rats, pigeons and monkeys trained to distinguish cocaine or methamphetamine from saline indicate that atomoxetine produces effects indistinguishable from low doses of cocaine or methamphetamine, but not at all like high doses of cocaine (Spealman, JPET 271:53, 1995; Sasaki et al., Psychopharm 120:303, 1995). No place preference studies have been conducted with atomoxetine.

Off-label Uses

The evidence of atomoxetine's efficacy on depression is somewhat contradictory. While Lilly's official trials indicated no improvement for depressed patients, many individuals, especially those with treatment-resistant depression, have seen significant positive results.^{[citation needed]}