Possible neurobiological mechanisms underlying faster onset of antidepressant action

All antidepressant drugs have a delayed onset of action. There is, however, evidence that some agents may attenuate depressive symptoms more rapidly than others. The present review examines the mechanisms by which selective serotonin reuptake inhibitors, the dual 5-HT norepinephrine reuptake inhibitor venlafaxine, and the alpha2-adrenoceptor antagonist mirtazapine alter 5-HT and/or norepinephrine neurotransmission. Particular attention is given to the time course with which these effects manifest themselves in relation to the possibility that these 3 types of drugs may act more rapidly, or exert a greater antidepressant action, than other agents. Based on the effects of antidepressant drugs presently available, strategies to accelerate or augment the antidepressant response are described, some of which have already been examined in patients.