Norepinephrine and Antidepressants


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 creation of desired behavioral effects of most classes of antidepressant compounds including the SSRIs.

in fact, norepinephrine was the first endogenous chemical linked with depression. for me SSRIs totally do not help and make things worse, NERIs or just "ok" and opioids or other good reward drugs are the only thing i really respond too.

My doctor lets me have a low dose of the non-controled, mild synthetic opioid tramadol (Ultram). other than that i remain untreated with treatment resistant major depression becuase ive tried everything else already.

the tramadol is actually the most decent thing i have had, better than regular opioids. regular opioids kick in fast then start letting you down right away. tramadol kicks in slow and stays consistent with a long platue and is more stimulating.

anyway, to stay on the topic of norepinepherine, not only is tramadol a milder mu agonist, but it also inhibitors norepinephrine and serotonin reuptake. judging from the subjective feeling of it alone, id have to guess it has more affinity for norepinephrine than serotonin.

I tried Atomoxetine (Strattera), the norepinephrine reuptake inhibitor, and i can say without hisitation that for me, its a whole lot better than SSRIs. sometimes it fought social anxiety well too but then after a few weeks it wasnt working as well and i just decided to quit it rather than go up in dose, because it still had side effects and didnt feel clean. still it was cleaner than those icky SSRIs. it was a good thing i went off of it anyway because i got tramadol next.

P.S. i dont like MAOIs =(