SSRIs

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SSRIs have just one direct effect - they block the nerve cells' reuptake of serotonin. Hence the name selective serotonin reuptake inhibitors (SSRIs).

Each time a nerve cell is stimulated, serotonin and other neurotransmitters are released into the synaptic cleft. Most of them are then reabsorbed into the nerve cell and recycled. SSRIs block this serotonin transport mechanism, preventing its reuptake.

This means that the serotonin receptors on the next cell are activated with higher then normal levels of serotonin and for a longer time. As a result, the cell will be stimulated more than usual. It is this increased serotonergic stimulation that helps people with depression.

Although the SSRIs have only one direct effect - inhibiting serotonin reuptake - they have many indirect effects:

The elevated levels of serotonin in the synaptic clefts affect the serotonin receptors in many different parts of the brain. This means that SSRIs impact on many different functions. This can explain the side effects associated with treatment with SSRIs... More about Serotonin.

Why do antidepressants take a few weeks to begin to work?

There are a number of unsolved mysteries in depression research - and the same goes for research into antidepressant drugs.

One of the mysteries when it comes to the biological effects of these drugs relates to the inhibition of serotonin reuptake in the brain. This inhibitory effect seems to begin very quickly after treatment starts.

The antidepressant drug rapidly impacts on the function of the nerve cells but its antidepressant effects:

• Sometimes never appear at all
• Sometimes take three to six weeks to appear
• Do not appear for at least two weeks after treatment starts

There are various possible explanations for this and it is currently uncertain which is responsible.

One explanation is that there will be a time lag between the start of any medicinal treatment and the medicine being distributed to the right places and beginning to exert its action.

Another is that the increase in serotonin and noradrenaline in the synaptic cleft results in the over stimulation of the receptors. This over stimulation will result in the nerve reducing the number of receptors. It may be only when the number of receptors decreases that the antidepressant effect will emerge.

A third explanation is that some of the serotonin receptors form part of a negative feedback mechanism, which slows down the whole serotonin system if it becomes too active. At the start of antidepressant treatment, when all the serotonin receptors are over stimulated, the feedback mechanism will be activated so intensely that the whole serotonin system may be paralysed. This is the exact opposite of the intended effect of the treatment. Only once the receptors involved in the feedback mechanism have acclimatized will the desired activation of the serotonin system - and so the desired antidepressant effect - kicks in.