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Selective serotonin reuptake inhibitor

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 synapses. 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.

Like other antidepressants, SSRIs are not addictive. 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 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. Third, the first letter of SSRI standing for "selective" indicates that not all synapses are affected, but only selectively those that are responsible for the the mood and, thus, the depression.

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

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