Possible Neurobiological Mechanisms Underlying Faster Onset of Antidepressant Action

All antidepressant drugs have a delayed onset of action. There is, however, evidence that someagents may attenuate depressive symptoms more rapidly than others. The present review examines themechanisms by which selective serotonin reuptake inhibitors, the dual 5-HT norepinephrine reuptakeinhibitor venlafaxine, and the α₂-adrenoceptor antagonist mirtazapine alter 5-HT and/or norepinephrineneurotransmission. Particular attention is given to the time course with which these effects manifestthemselves in relation to the possibility that these 3 types of drugs may act more rapidly, or exerta greater antidepressant action, than other agents. Based on the effects of antidepressant drugs presentlyavailable, strategies to accelerate or augment the antidepressant response are described, some ofwhich have already been examined in patients.