Originally Posted by
panic_down_under
But it does often enough to make trying higher doses worthwhile, Terry. If my doctors had not explored the upper dose limits I would have been leading the life of what the Japanese call a 'Hikikomori', a recluse imprisoned by agoraphobia, for the last 30 years.
Marketing is probably the major factor, but also most antidepressants were developed before their binding potential could be measured so their supposed effects were based mostly on circumstantial evidence and a fair amount of guessing. Even now binding assays are far from precise, with a 5-10 fold variation quite common even when tested by the same lab. Much of the data is also based on non human receptors and transporters which may reduce its value.
Plus, these are lab results which may or may not reflect what actually happens in a living brain. One of the reason the low serotonin hypothesis gained early credibility is that in test tubes antidepressants do what the hypothesis proposes. It was only dispelled when the invention of microdialysis pipettes allowed researchers to test the hypothesis within living brains. I remember reading a mid 1990s by Chantal Moret and Mike Briley in which they repeated an in vitro experiment they'd done a few years previously, this time using in living rats instead of rat brain slices, and being puzzled by the results failing to replicate the earlier finding. Researchers don't often express surprise in their papers, but they did.