SSRIs exert a neurogenic effect on the hippocampus and increase the amount of neurotrophic factors there, and also alter the count/ratio of certain serotonin receptors.

To my knowledge this behavior isn't readily found in placebo trials when comparing against SSRIs, and a placebo would not be able to target a certain region.

Serotonin releasing agents(or rather tri-amine releasing agents) were some of the first antidepressants ever made, and were extremely successful. Consequently they had some severe side effects, and also sometimes worked "too well"(causing euphoria) so they had a short lived existence.

Example being a-met