Selective serotonin reuptake inhibitors (SSRIs) are the focus of extensive research into finding beneficial pharmacological therapies. There is evidence that serotonergic pathways are the most closely related systems to mood disorders, especially depression, and thus SSRIs may lead to significant therapy. Clinical depression is one of the most common psychiatric disorders, with an incidence of about 4% and a life-time prevalence of 15-20%. Despite significant research, the neurobiological dysfunctions of major depression remain elusive. Findings implicate multiple abnormalities in serotonergic pathways in the cause of depression. Findings include 1) low concentrations of the major serotonin metabolite; 2) a low density of brain and platelet serotonin transporters in depressed individuals; 3) a high density of brain and platelet serotonin binding sites; and 4) a low concentration of tryptophan which is used in serotonin synthesis. Of these, the low level of SERTs in depressed patients has received the most attention. Still, while the precise cause of depression eludes neuroscientists, SSRIs have been shown to alleviate the mood disorder and are a common therapy for depression.

Fluoxetine, more commonly Prozac, is one antidepressant SSRI that has been a popular topic in medical as well as social and psychological discussions. Because of increased selectivity as compared to previous drugs (such as tricyclics and non-selective MAO inhibitors which have affinity for amines, acetylcholine, and norepinephrine transporters), SSRIs produce significantly fewer unwelcome side effects because they work exclusively on serotonin pathways.

Fluoxetine blocks SERT activity immediately, however, therapeutic effects are seen only after 2-3 weeks of treatment. A patient given Prozac may experience greater depression before feeling better. Initially, a SERT antagonist blocks the reuptake process, extracellular serotonin remains elevated and can activate receptors at greater distances from the presynaptic neuron. High levels of serotonin over an enduring time period create changes in the amount of pre- and postsynaptic receptors, the amount of serotonin produced, as well as in the number of SERTs expressed. Neurons may set the level of SERT expression based on the level of clearance needed. An increase in serotonin creates a change in SERT expression and consequently effects mood and other serotonin affected behaviors. It is these compensatory responses at receptors and transporters that is thought to produce therapeutic effects.

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