Serotonin-norepinephrine reuptake inhibitor

Overview
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used in the treatment of clinical depression and other affective disorders. They are also sometimes used to treat anxiety disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD) and chronic neuropathic pain. They act upon two neurotransmitters in the brain that are known to play an important part in mood, namely, serotonin and norepinephrine. This can be contrasted with the more widely-used selective serotonin reuptake inhibitors (SSRIs), which act only on serotonin.

Mode of action
Activity on norepinephrine reuptake is thought necessary for an antidepressant to be effective on neuropathic pain, a property shared with the older tricyclic antidepressants but not with the SSRIs.

Depression is thought to be caused by a lack of information flow between neurons in certain parts of the brain. Neurons pass information to each other by means of chemicals known as neurotransmitters, which shoot across the tiny synapses between the cells. After firing, most of the neurotransmitter is reabsorbed by the presynaptic cell in a process called reuptake.

Antidepressants work by increasing the number of neurotransmitters active in the synapse, thereby enhancing neuronal activity and increasing the responsiveness of mood. Modern antidepressants usually achieve this effect by blocking the transporter proteins that reabsorb certain neurotransmitters, hence the name "reuptake inhibitors".

SNRIs were developed more recently than SSRIs, and there are relatively few of them. Their efficacy as well as their tolerability appears to be somewhat better than the SSRIs, owing to their compound effect.

Adverse effects
As with the SSRIs, abrupt discontinuation of SNRI-medication usually leads to a discontinuation syndrome which could include states of anxiety and further symptoms. It is therefore recommended to slowly taper down the dose under the supervision of a psychopharmacologist when discontinuing SNRIs. Due to the effects on increasing Norepinephrine synaptic activity, these drugs are contraindicated in patients with hypertension, heart disease, or risk of stroke.

SNRIs currently available

 * venlafaxine (tradenames Effexor XR®, Effexor®) is the first and most commonly used SNRI. Although it also works on dopamine somewhat at high dosages, the majority of its effect is on serotonin and norepinephrine.


 * desvenlafaxine (tradename Pristiq®) is the active metabolite of venlafaxine and is believed to work in the same manner. It will be introduced by Wyeth in late 2007-early 2008.


 * nefazodone (tradename Serzone®) is an antidepressant with efficacy similar to SSRIs, but without the sexual side effects. In fact, Serzone at times may act similarly to Wellbutrin in its neutral or at times positive effect on function. It has been discontinued in several countries due to rare cases of liver failure. The tradename "Serzone®" has been discontinued, however generic nefazodone is currently available (May 06). However, the liver failure is rare, and a simple blood test every 6 months to assess liver enzyme levels is sufficient.  Nefazodone has an active metabolite which at higher doses (> 250mg/day) can increase anxiety.  One of the benefits nefazodone has over Effexor® and  Cymbalta® is its enhanced sedation when taken at bedtime.


 * milnacipran (tradename Dalcipran®/ Portugal; Ixel®/ France) has shown to be significantly effective in the treatment of depression and Fibromyalgia syndrome (FMS). Although it has not yet been approved by the Food and Drug Administration (FDA) for use in the United States, it has been commercially available in Europe and Asia for several years.


 * desipramine (tradenames Norpramine®, Pertofraneis®) is technically a tricyclic antidepressant, and is usually categorized as such. It works, however, on both serotonin and norepinephrine, so it can also be considered an SNRI.


 * duloxetine (tradename Cymbalta®) by Eli Lilly and Company, also inhibits serotonin reuptake and has been approved for the treatment of depression and neuropathic pain in August of 2004.

Please note that some of the above medications may not be considered "true" SNRIs; refer to specific peer-reviewed scientific journals for more in-depth coverage on classifications and pharmaco-kinetics.