Serotonin and norepinephrine are two neurotransmitters that are identified as having strong effect on mood and many forms of mental or other illness, together or separately. If these chemicals exist in appropriate amounts and are not used too quickly by receptors in the brain, this often corresponds to more even mood. When they are used (reuptake) too quickly, mood may be difficult to control and conditions like depression or anxiety could occur. To greater or lesser degree, they also seem to have an impact on conditions like attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder or illnesses that cause chronic pain, such as fibromyalgia. Depending on the condition, medication that prevents quick reuptake of one or both of these neurotransmitters may be needed.
Even though serotonin and norepinephrine have similar roles, they’re not identical. Most serotonin resides in the gastrointestinal (GI) system and assists in GI tract function. Medications that increase this neurotransmitter’s levels (selective serotonin reuptake inhibitors or SSRIs) can sometimes cause gastric problems. The principal location of most serotonin also offers explanation for why food consumption and mood are sometimes related. Only about 20 percent of the serotonin in the body circulates through the central nervous system.
In contrast, norepinephrine in produced in the sympathetic nervous system and it can be released in high amounts by the adrenal glands during fight or flight responses. In addition to affecting mood stability, norepinephrine also seems indicated in helping to increase cognitive focus. “Antidepressant" medications used in the treatment of ADHD are often ineffective if they don’t inhibit the reuptake of norepinephrine.
Drug research has led to numerous medications that most specifically target serotonin levels. With the advent of tricyclic drugs, some medications began to act as reuptake inhibitors to both serotonin and norepinephrine. This meant they prevented receptors for these chemicals from initiating a reuptake process too quickly, giving the brain more access to available serotonin, as well as norepinephrine. Tricyclics had a heavy burden of side effects, and they were replaced by medications that acted on serotonin only — SSRIs.
It became evident that many people with depression or anxiety were not fully helped by SSRIs, and drug researchers developed a new set of medicines that again addressed norepinephrine and serotonin reuptake. These are called serotonin and norepinephrine reuptake inhibitors or SNRIs. Common SNRIs presently available include venlafaxine (Effexor®), desvenlafaxine (Pristiq®), and duloxetine (Cymbalta®). A few of the tricyclics are being re-branded as SNRIs and it’s unclear that side effect profiles of tricyclics and SNRIs are truly that different.
Research also suggests that certain conditions will respond better to SNRIs. Phobias, ADHD, generalized anxiety disorder, and major depressive disorder all might be best treated with a norepinephrine and serotonin reuptake inhibitor. This isn’t always the case, however, so treatment varies with the individual. There are disadvantages to drugs that simultaneously act on both neurotransmitters, including tendency to create discontinuation syndrome, which is similar to withdrawal. Additionally, inappropriate use of SNRIs in people with undiagnosed bipolar disorder may readily create mania or hypomania.