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.

Activity on norephinephine 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 amount 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 neurotranmitters, 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. It is expected that most future antidepressants will probably work on multiple neurotransmitters, like the SNRIs and novel antidepressants such as bupropion (tradenames Wellbutrin® and Zyban®).

SNRIs currently available:

• Venlafaxine (tradename 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.

• Nefazodone (tradename Serzone®) is an antidepressant with efficacy similar to SSRIs. It has been discontinued in several countries due to rare cases of unexpected liver failure.

• Milnacipran (tradename Ixel®) has shown to be significantly effective in the treatment of depression and Fibromyalgia syndrome (FMS). Although it has not yet been approved by the 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®) is a new SNRI by Eli Lilly and Company, and has been approved for the treatment of depression and neuropathic pain in August of 2004.