Adrenaline Packs A Powerful Punch In The Use Of Antidepressants
Philadelphia, PA -- Researchers from the University of Pennsylvania School of Medicine found that
norepinephrine (adrenaline) plays an important role in animals in determining behavioral effects in some of the
most commonly prescribed antidepressants, regardless of which biochemical pathway the drug uses to
alleviate symptoms of depression. This finding -- published in the May 2004 Proceedings of the National
Academy of Sciences -- should help scientists design more effective drugs for patients. Using genetically-altered mice unable to produce norepinephrine, they tested behavioral changes brought on
by two different antidepressant classes. With the exception of one drug, they found that those lacking
norepinephrine did not respond to the drugs. "Millions of Americans suffer from major depressive disorders
and this study helps us understand how antidepressant drugs are processed to produce clinical therapeutic
effects. It helps us understand how to redesign better drugs and which treatments will work better for which
patients," says the study's lead author, Irwin Lucki, PhD, Professor of Psychiatry and Pharmacology and
Director of the Behavioral Psychopharmacology Laboratory at Penn. There are currently two major classes of antidepressants used to treat depression: norepinephrine reuptake inhibitors (which work by increasing the synaptic activty of adrenaline in the brain); and selective serotonin
reuptake inhibitors (which elicit their effects by increasing the activity of serotnin in the brain). Previously, it was believed that SSRIs ? whose over-the-counter names include Prozac, Zoloft, Paxil, and
Celexia ? produced effects on the serotonergic system only; but the Penn researchers' findings showed that the effects of most SSRIs can also depend on responses
from the noradrenergic system. "This study is the first to use this unique animal model to test whether the
drugs are still effective in animals that lack norepinephrine, a key neurotransmitter in the brain," Lucki adds. The researchers tested eight commonly prescribed antidepressant drugs, including four SSRIs. The SSRI
medications tested were fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) and citalopram (Celexia). In
animal models, those able to produce norepinephrine experienced behavioral changes when given the
antidepressants. But all of the antidepressants, except citalopram, failed to work in the models lacking
norepinephrine. These results provide striking evidence that norepinephrine plays a critical role for the