In depressed patients, antidepressants treatment typically takes 2-3weeks before it exerts its beneficial effect. It is believed that the underlying mechanism for antidepressant therapeutic effects is a remodeling of the strength of the synapse. In fact, antidepressant treatment induces the increase in expression of genes such as the neurotrophic factor BDNF, as well as other genes involved in synaptic plasticity , such as Arc, which encodes a protein of the cytoplasm , VGLUT1, which encodes a protein involved in the storage of vesicular glutamate in the presynaptic element, SHANK1B, a protein of the postsynaptic density which functionally and physically linked the metabotropic and the ionotropic glutamatergic receptors as well as binding Homer1A.
We demonstrated that the expression of the genes involved in synaptic plasticity are expressed in a time-and region-dependent manner during antidepressant treatment, suggestive of a remodeling of the synapse.
During the 2-3 weeks delay before antidepressants produce their therapeutic effect on the mood, patients are very vulnerable to suicidal thoughts. It is therefore very important to try and find ways to shorten the therapeutic onset of antidepressants. One way is to combine antidepressant treatment with other drugs such as alpha2 adrenoceptor blocker.