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How Antidepressants Work Presented by Rainsville Family Practice Thomas L. Horton, MD Seratonin particles Neuron Synapse Receptor sites These symbols represent neurons or nerve cells in the brain. Thoughts and impulses are transmitted by neurons through tiny electric currents and messages carried by chemicals called neurotransmitters. The neurotransmitter we are discussing with regard to depression is seratonin. Neuron Seratonin Synapse When a neuron is activated, it releases seratonins into the synapse. These particles migrate across the synapse and activate the receptor sites on the next neuron, thus stimulating that neuron and relaying the impulse. After stimulating the receptor sites, the seratonins return to the first neuron and are reabsorbed to await the next impulse. The second neuron releases seratonins into the next synapse, and activates the third neuron. This process is repeated over and over until the impulse has been transmitted to the desired location in the brain. Clinical depression (in contrast to simple sadness, grief, etc.) is caused by, or exacerbated by, a deficiency of seratonins. This may be related to genetic predisposition, chronic stress, or illness, certain medications, or by other factors we do not fully understand. In any event, the first neuron cannot secrete enough messengers to activate the receptor sites adequately on the next neuron, therefore the signal is muted. The end result of a series of inadequate signals is the condition we recognize as depression. Antidepressants such as the seratonin reuptake inhibitors (SSRI’s) work to amplify the signal and make the brain function more normally. The seratonins are released normally and activate the receptor sites as usual. However, instead of being reabsorbed, they are blocked from returning to the first neuron. Think of it as “Gortex for the brain.” The particles can get out, but they cannot easily return. They are then free to activate more receptor sites. This allows the existing seratonins to create a stronger signal than would otherwise be possible. When the first neuron fails to reabsorb the seratonins, it begins to make new seratonin particle to replace the ones it is missing. This process may take weeks or months to completely restore a normal amount of seratonin. This is the reason we recommend taking SSRI’s for six months before stopping them. While some people seem to benefit from continued use after six months, it is hoped that most patients will have returned their seratonin levels to normal and will not need the support of the medication after six months.