Quote Originally Posted by panic_down_under View Post
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.
I don't disagree, Ian. For many that extra helps greatly, it's just that for some the med is a dud and they switch and maybe even increase with that until they find what works. But GP's can also be a bit over zealous upping doses far too quickly or even when the patient is responding well already.

I can understand the drugs companies trialling, getting licenced and then never caring as the watch their reps pull the cash in for them. But the medical professionals you would think would be altering the status of drugs where needed. It just seems led by the companies with often little interest from the docs in changing things because the drugs are plastering over problems in patients.