Models of antidepressant action

Although immediate pharmacologic targets can be identified for most antidep ressant treatments, elucidation of the critical biological mechanisms leadi ng to symptom relief has defied decades of research. Tn this review, select ed neurotransmitter, biochemical, and anatomic models of antidepressant act ion are considered with regard to their explanatory power and therapeutic a pplicability. Monoamine models have been a focus of research attention on a ntidepressant action, an appropriate emphasis in that virtually ail antidep ressant medications have high affinity for monoamine substrates. Furthermor e, prevailing monoamine models have suggested some promising therapeutic st rategies. Nevertheless, these models are ultimately incomplete and do not f ully explain important clinical limitations of current treatment: delayed r esponse, incomplete efficacy, and unsustained remissions. Continued therape utic advancements will likely require the development of models of antidepr essant action that extend beyond the monoamines.