This medication is a norepinephrine reuptake inhibitor, initially developed as an antidepressant. It was brought to the market as the first drug for adult ADD, rather than one of the last for depression. It differs notably from other “stimulants” though in its mechanism and risks.
In early clinical trials, this agent was found to be effective in major depressive episodes. It was noted that it shared its basic mechanism of pure norepinephrine effects with desipramine, which had been proven effective in childhood ADD. Eli Lilly, the company which was developing atomoxetine, made an economic decision to shift to ADD, rather than major depressive disorder (MDD), but even in ADD, there were multiple other agents, mostly amphetamines, that were FDA-indicated in children. However, no agents were FDA-indicated in adults for ADD. Indeed, the whole concept of adult ADD was not used much, and it was not part of DSM-IV.
After obtaining academic support, Eli Lilly convinced the FDA to provide the first indication for ADD in adults. The latter designation was then added to DSM-5.
Atomoxetine blocks reuptake of norepinephrine at the synapse. Unlike other “stimulants” it does not have direct or indirect agonism of dopamine activity.
The main side effect of this agent, as with the other pure noradrenergic drug desipramine, is anxiety and feeling agitated or overstimulated. Desipramine, which is a tricyclic antidepressant, was also associated with cardiac arrhythmias, but this has not been the case with atomoxetine.
The clinical trials with atomoxetine showed some cases of increased suicidal thoughts with this agent, versus no cases with placebo, which led to a FDA black-box warning in 2005.