Alex You may be right but I am suspicious of categorical statements! And serotonin is not the same as serotonergic systems. What would you say about positive responses to HTP, 5HTP? It could be argued on your lines of "serotonin and sth else" that e.g. they work on depression because they raise niacin or sth. too. We don't know. Also since serotonin is neurochemically active is it not possible that in some patients raising serotonin will directly improve mood. Or indeed worsen it? I agree that the SSRI's work by rasing serotonin line is simplistic and I don't think the informed advocates of these drugs would maintain this. But interfering with serotonin systems does seem to affect mood. In Europe (not here in the UK) there is at least one SSREnhancer, (tianeptine) with an opposite action from SSRI's but effective in depression.