Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive–compulsive disorder responses

Considerable evidence is now available to support the pivotal role of the serotonin (5-HT) system in exerting the antidepressant response in humans. Different types of antidepressant treatments enhance 5-HT neurotransmission via different pre- or postsynaptic mechanisms. The time course for the occurrence of these adaptive changes in the brain of laboratory animals is consistent with the delayed onset of the antidepressant response in humans. The drugs effective in obsessive–compulsive disorder (OCD) also enhance 5-HT neurotransmission in brain regions involved in mediating OCD symptoms but with a more prolonged delay, consistently with the longer time necessary to obtain an optimal therapeutic effect in OCD than in depression. The elucidation of these mechanisms of action lead to the development of new pharmacologic strategies to potentiate the therapeutic effect of the drugs currently available and to the identification of novel targets to accelerate and further improve treatment response in depression and OCD.