Older antidepressant drugs included tricyclic antidepressants like doxepin (Adapin, Sinequan) and imipramine (Tofranil), as well as monoamine oxidase inhibitors (MAOIs) like phenelzine (Nardil) and tranylcypromine (Parnate). MAOIs prevent the breakdown of monoamine neurotransmitters (including serotonin), and therefore increase concentrations of the neurotransmitter in the brain. MAOI therapy has been associated with many adverse drug reactions, unlike the newer class of SSRIs like citalopram (Celexa), paroxetine (Paxil), fluoxetine (Prozac), sertraline (Zoloft), as well as the SNRI’s like Venlafaxine (Effexor) and duloxetine (Cymbalta). Other antidepressant drugs include bupropion (Wellbutrin), buspirone (Buspar), and nefazodone (Serzone).
SSRIs and SNRIs affect the chemicals that nerves in the brain use to send messages to one another. These chemical messengers, called neurotransmitters, are released by one nerve and taken up by other nerves. Neurotransmitters are chemicals released from a nerve cell which transmit an impulse from a nerve cell to another. When these messengers of neurologic information are not taken up by other nerves, are taken up by the same nerves that released them back to their storage vehicles for later use. This process is termed “reuptake.” Selective serotonin reuptake inhibitors (SSRIs) work by inhibiting the reuptake of serotonin, which allows more serotonin to be available to be taken up by other nerves. Serotonin-norepinephrine reuptake inhibitors (SNRIs), on the other hand, increase the amount of serotonin and norepinephrine available to postsynaptic cells in the brain.
- Serotonin is a neurotransmitter responsible for overall feelings of well-being. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, obsessive-compulsive disorder (OCD), and many others.
- Norepinephrine (a.k.a. noradrenaline) basically controls alertness and arousal. Along with dopamine, norepinephrine has come to be recognized as playing a large role in attention and focus. It is released from adrenal glands as a hormone into the blood, but it is also a neurotransmitter in the nervous where it is released from noradrenergic neurons during synaptic transmission. Along with epinephrine, norepinephrine underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing skeletal muscle readiness.
- Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment and reinforcement to motivate a person proactively to perform certain activities. Dopamine also has important roles in behavior and cognition, motor activity, and many others. There is some recent evidence showing that the norepinephrine transporter also transports some dopamine as well, implying that SNRIs may also increase dopamine transmission. Therefore, the antidepressant effects associated with increasing norepinephrine levels may also be partly due to the concurrent increase in dopamine.