I suspect that their overall effect is underestimated because they [have high variance]
Averaging is the right thing to do. High variance with zero mean really has zero mean.
If the drug is used differently in the field than in the studies, the studies may be misleading. In particular, if the patient tries several drugs, looking for one with positive effect, high variance of the individual drugs yields an overall positive outcome (if the drugs are not correlated). Some people claim that antidepressants are used this way, but others claim that they are used blindly.
Yes, the effect is usually stable for the same person on the same drug, so it's standard procedure to try a lot of antidepressants until one helps. Who claims that it's not? I've never heard of that, and it just sounds completely weird that a doctor wouldn't adjust treatment depending on results.
That's why averages aren't enough data. High-variance meds are better as long as the worst case is rarely lethal, since bad effects are felt only for as long as it takes to notice and switch whereas good ones are forever.
My name is Brent, and I'm probably insane.
I can perform various experimental tests to verify that I do not perform primate pack-bonding rituals correctly, which is about half of what we mean by "insane". This concerns me simply from a utilitarian perspective (separation from pack makes ego-depletion problems harder; it makes resources harder to come by; and it simply sucks to experience "from the inside"), but these are not the things that concern me most.
The thing that concerns me most is this:
What if the very tools that I use to make decisions are flawed?
I stumbled upon Bayesian techniques as a young child; I was lucky enough to have the opportunity to perform a lot of self-guided artificial intelligence "research" in Junior High and High School, due to growing up in a time and place when computers were utterly mysterious, so no one could really tell me what I was "supposed" to be doing with them - so I started making simple video games, had no opponents to play them against due to the aforementioned failures to correctly perform pack-bonding rituals, decided to create my own, became dissatisfied with the quality of my opponents, and suddenly found myself chewing on Hopfstaedter and Wiener and Minsky.
I'm filling in that bit of detail to explain that I have been attempting to operate as a rational intelligence for quite some time, so I believe that I've become very familiar with the kinds of "bugs" that I will tend to exhibit.
I've spent a very long time attempting to correct for my cognitive biases, edit out tendencies to seek comfortable-but-misleading inputs, and otherwise "force" myself to be rational, and often, the result is that my "will" will crack under the strain. My entire utility-table will suddenly flip on its head, and attempt to maximize my own self-destruction rather than allow me to continue to torture it with endlessly recursive, unsolvable problems that all tend to boil down to "you do not have sufficient social power, and humans are savage and cruel no matter how much you care about them."
Most of my energy is spent attempting to maintain positive, rational, long-term goals in the face of some kind of regedit-hack of my utility table itself, coming from somewhere in my subconscious that I can't seem to gain write-access to.
Clearly, the transhumanist solution would be to identify the underlying physical storage where the bug is occurring, and replace it with a less-malfunctioning piece of hardware.
Hopefully someday someone with more self-control, financial resources, and social resources than I will invent a method to do that, and I can get enough of a partial personectomy to create something viable with the remaining subroutines.
In the meantime, what is someone who wishes to be rational supposed to do, when the underlying hardware simply won't cooperate?