Fluoxetine (Prozac) Since Its Approval for Use

Fluoxetine (Prozac)

Since its approval for use in the United States by the FDA in 1987, fluoxetine (commonly known as Prozac) has been the subject of great debate. Fluoxetine, now available in generic form, has been proven useful in the treatment of depression, anxiety, obsessive-compulsive disorder, some eating disorders, panic disorder, insomnia, migraines, schizophrenia, and more (Schmetzer, 2002). However, this drug does have a range of possible side effects including sexual dysfunction, anxiety, insomnia, agitation, tremors, irritability, hypomania, impulsivity, and gastrointestinal distress (Kerr, 2008). In addition, it may be too early to tell what the consequences of long-term (more than 20 years) use of fluoxetine might be on the human brain (Murray, 2006).

As a psychoactive drug, fluoxetine works by affecting the neurotransmitters serotonin and norepinephrine. Neurotransmitters in the brain are synthesized in neurons, stored in vesicles, and upon nerve impulse stimulation, are released into the synaptic cleft. Here they interact with certain receptor neurons to produce their various effects. The actions of both serotonin and norepinephrine are dissolved by diffusion, metabolism, or reuptake (Borne, 1994). Fluoxetine belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRIs), because of its potent inhibition of serotonin reuptake at transmitter neuron synapses. In some people, the brain seems to excessively reabsorb the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) after release, presumably to save chemical energy through frequent reuse. However, this efficiency can result in depression if it takes place too quickly; in these cases, the serotonin never has a chance to activate the receiver neuron. This is where SSRIs such as fluoxetine come in; they "selectively" inhibit this hyper-efficiency of uptake, prolonging and magnifying the effects of serotonin in the synapses (Olfson, 2002) Serotonin, when functioning properly as a neurotransmitter, affects "appetite, sleep, memory and learning, temperature regulation, mood, behavior (including sexual and hallucinogenic behavior), cardiovascular function, muscle contraction, endocrine regulation, and depression (Borne, 1994)." In addition, serotonin has analgesic, pain-suppressing effects which are not fully understood (Borne, 1994).

Serotonin is a fascinating neurotransmitter; scientists have already discovered more than 15 different subtype categories of serotonin receptors geared to perform different functions affecting the nervous system. These include (to name just a few): 5-HT sub 1A, which is known to affect sexual behavior, food intake, body temperature, and depression; 5-HT sub 1C, is involved in analgesia, sleep, and function of the cardiovascular system; 5-HT sub 1D, shown to have an effect on migraine headaches; and 5-HT sub 3, receptors apparently involved in aspects of anxiety, cognitive, and psychotic abnormalities (Borne, 1994).