How do SSRI's work?

Answer 1

Selective serotonin reuptake inhibitors (SSRIs) achieve their therapeutic effect by modifying synaptic availability of the neurotransmitter serotinin. This is accomplished, first of all, by blocking the proteins that normally transport serotonin back into the cells that release them (presynaptic cell). In doing so, synaptic levels of serotonin are temporarily boosted. This phase is normally associated with an acute increase in anxiety. However, this subsides over several days as subtypes of postsynaptic5-HT receptors down-regulate in response to the excess serotonin. During this time another kind of protein called an autoreceptor (in this case 5-HT1 autoreceptors) located on the presynaptic cell begins to desensitize. Normally these types of receptor proteins provide a kind of feedback mechanism that limits the production of neurotransmitters.With these desensitized, the cell receives less feedback and the rate of serotonin synthesis and release increases. Since not all postsynaptic 5-HT receptors down-regulate in response to increased synaptic levels of serotonin - the ones that don't are able to bind more serotonin and this is thought to account for the longer term effects of SSRIs. Similar processes occur as 'secondary effects' on cells that release noradrenaline - as these express 5-HT2a heteroceptors - and this also is thought to contribute to their therapeutic efficacy. The reason serotonin is targeted by SSRIs in the first place is that the same regions of the brain that contain a high density of serotinin-releasing neurons (Raphe nuclei) are known to regulate mood directly as well as indirectly via interactions with other brain areas and neurotransmitter systems (like noradrenaline and dopamine in other parts of the limbic system as well as frontal cortex). However, because it's so complex, and no two brains are the same, responses to SSRIs can vary. In most cases of mild to moderate depression they offer a benefit .

Answer 2

It is observed in post-mortem examinations of depressed people that committed suicide that serotonin levels were low at some parts of the brain. SSRI's reduce the rate of destruction of serotonin therefore increasing it's concentration.

SSRIs definitely increase serotonin levels in all patients immediately, but anti-depressant action is NOT guaranteed and when it is achieved, it is after 20 days or more. So other factors may be contributing as well, but they are yet to be discovered.