On 2017 Apr 13, Konstantinos Fountoulakis commented:

This paper discusses possible mechanisms of antidepressant effect 1. Although the whole discussion is intriguing, it should be noted that the fundamental assumption of the authors is mistaken. More specifically, the authors start from the position that there is a latency time of approximately two weeks from initiation of antidepressant treatment to the manifestation of the treatment effect. This is an old concept, now proven wrong. We now know that the treatment response starts within days and it takes two weeks not for the treatment effect to appear but for the medication group to separate from placebo 2. This conclusion is so solid that it has been incorporated in the NICE CG90 guidelines for the treatment of depression (available at https://www.nice.org.uk/guidance/cg90/evidence/full-guidance-243833293, page 413). These two are completely different concepts, often confounded in the literature. However it is clear that medication significantly improves the chances of a patient to be better after two weeks in comparison to placebo, but improvement itself has started much earlier. We also know that the trajectories of patients we respond to medication are similar to the trajectories of those who improve under placebo. One of the possible consequences of this observation is that there might not be a physiological difference underlying response under medication in comparison to response under placebo; however the chances these physiological mechanisms are activated are higher under medication References 1. Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. The lancet Psychiatry 2017. 2. Posternak MA, Zimmerman M. Is there a delay in the antidepressant effect? A meta-analysis. The Journal of clinical psychiatry 2005; 66(2): 148-58.

On 2017 Apr 13, Konstantinos Fountoulakis commented:

This paper discusses possible mechanisms of antidepressant effect 1. Although the whole discussion is intriguing, it should be noted that the fundamental assumption of the authors is mistaken. More specifically, the authors start from the position that there is a latency time of approximately two weeks from initiation of antidepressant treatment to the manifestation of the treatment effect. This is an old concept, now proven wrong. We now know that the treatment response starts within days and it takes two weeks not for the treatment effect to appear but for the medication group to separate from placebo 2. This conclusion is so solid that it has been incorporated in the NICE CG90 guidelines for the treatment of depression (available at https://www.nice.org.uk/guidance/cg90/evidence/full-guidance-243833293, page 413). These two are completely different concepts, often confounded in the literature. However it is clear that medication significantly improves the chances of a patient to be better after two weeks in comparison to placebo, but improvement itself has started much earlier. We also know that the trajectories of patients we respond to medication are similar to the trajectories of those who improve under placebo. One of the possible consequences of this observation is that there might not be a physiological difference underlying response under medication in comparison to response under placebo; however the chances these physiological mechanisms are activated are higher under medication References 1. Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. The lancet Psychiatry 2017. 2. Posternak MA, Zimmerman M. Is there a delay in the antidepressant effect? A meta-analysis. The Journal of clinical psychiatry 2005; 66(2): 148-58.