Аннотация:The serotonin hypothesis of depression has played an important role in the history of psychiatry, yet it has also been criticized for the delayed onset and inadequate efficacy of SSRIs. With evolvement of neuroscience, the neuroplasticity hypothesis of major depressive disorder (MDD) has been proposed and may provide a better framework for clarification the pathogenesis of MDD and antidepressant efficacy. In this paper, we firstly summarized the evidence challenging the monoamine hypothesis and proposed that the antidepressant efficacy of SSRIs is not derived from elevated monoamine (serotonin, noradrenaline, or dopamine) concentration or monoamine neurotransmission. Secondly, we reviewed the role of stress in the pathogenesis of MDD and gave a brief introduction to the neuroplasticity hypothesis of MDD. Thirdly, we explored the possible mechanisms underlying the antidepressant efficacy of typical antidepressants in the context of neuroplasticity theory. Fourth, we tried to provide an explanatory framework for the significant difference in onset of efficacy between typical antidepressants and ketamine. Finally, we provided a brief summarization about this paper and some perspectives for future studies.
