Table of Contents

Volume 1, Issue 11                                                                                 November, 2015

Drug of the Month:

An antidepressant masquerading as an ADD drug

Atomoxetine structure

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. 

Clinical efficacy and inefficacy

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.  

Biological mechanism

Atomoxetine blocks reuptake of norepinephrine at the synapse.  Unlike other “stimulants” it does not have direct or indirect agonism of dopamine activity.  

Fast facts: Atomoxetine

Typical dose:  40-80 mg/d ( range: 10-100 mg/d )

Biological mechanism: Norepinephrine reuptake inhibitor

Typical side effects: anxiety, insomnia

Less common but important side effects: none

Medically important side effects:  none

Clinically proven efficacy: Treatment of major depressive episodes and ADD

Side effects and dosing

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.

The PL Bottom Line

  • Atomoxetine is an antidepressant masquerading as a “stimulant” for adult ADD. 
  • It is a norepinephrine reuptake inhibitor, like desipramine, which tends to cause anxiety.

PL Reflection

And what goal could be more sacred than that of caring for a brother in distress, especially when the affliction is distinctly human and therefore more obvious than others, and when it respects neither reason nor rank nor riches?

R Emil Kraepelin

One Hundred Years of Psychiatry

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