The Selective serotonin reuptake inhibitor reference article from the English Wikipedia on 24-Jul-2004
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Selective serotonin reuptake inhibitor

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Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants. They act within the brain to increase the amount of the neurotransmitter serotonin (5-hydroxy-tryptamine or 5-HT) by inhibiting its re-uptake at synapsess. One notable characteristic of SSRIs is that, unlike other classes of antidepressants, SSRIs were rationally designed drugs. Instead of being discovered by accident, SSRIs were specifically designed while considering the biological causes of depression. SSRIs can also be used to treat anxiety disorders, obsessive-compulsive disorder, and eating disorders.

SSRIs are not thought to be strictly addictive, but discontinuing their use is known to produce both somatic and psychological withdrawal symptoms, a phenomenon known as "SSRI discontinuation syndrome" (Tamam & Ozpoyraz, 2002). Their effectiveness does not appear to be higher than tricyclic antidepressants which were the most commonly used class of antidepressants before the SSRIs. However, SSRIs have the important advantage that the toxic dose is high, and, therefore, they are much more difficult to use as a means to commit suicide.

Many drugs in this class are familiar through advertising, including

In the brain, information is passed between two neurons (nerve cells) via a synapse, a small gap between the cells. The neuron that sends the information releases neurotransmitters (with serotonin among them) into that gap. The neurotransmitters are then recognized by receptors on the surface of the recipient cell, which upon this stimulation in turn relays the signal. About 10% of the neurotransmitters are lost in this process, the other 90% are released from the receptors and taken up again by monoamine transporters in the sending cell (thus reuptake).

Depression has been linked to a lack of stimulation of the recipient neuron at a synapse. To stimulate the recipient cell, SSRIs inhibit the reuptake of serotonin. As a result, the serotonin stays in the synaptic gap longer than it normally would, and has the chance to be recognized again (and again) by the receptors of the recipient cell, which can finally be stimulated that way.

Why not give serotonin directly? First, serotonin ingested orally will not cross the blood-brain barrier, and therefore won't have an effect on brain functions. Second, pure serotonin would turn on every synapse it reaches, whereas SSRIs only enhance a signal that is already present, but too weak to come through.

SSRIs are described as 'selective' because they affect only the reuptake pumps responsible for serotonin, as opposed to earlier antidepressants which affect other monoamine neurotransmitters as well. Because of this, SSRIs lack some of the side effects of the more general drugs.

Serotonin is made from tryptophan, an amino acid. If depression is caused by lack of serotonin, rather than insensitivity to it, SSRIs alone will not work well, whereas supplementing with tryptophan will. In 1989 the FDA made tryptophan available by prescription only in response to an outbreak of eosinophilia-myalgia syndrome caused by impure L-tryptophan supplements sold over-the-counter. Some critics have suggested that this appears to have been done to make money for the manufacturers of SSRIs.

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