Follow-up: Escalating every six weeks instead of four: what I observed over eight months

Escalating every six weeks instead of four: what I observed over eight months — setting out what I have, and where I think it stops being reliable.

Two things I would like separated before anyone answers on Escalating every six weeks instead, because they get bundled and then argued about as one thing.

The first is descriptive: what has actually been observed, by whom, and how. The second is causal: why. I am asking about the first only.

The four-week escalation interval is a convention from the pivotal trials, not a pharmacological constant. The pharmacological argument is that with a week-long half-life, four weeks approaches steady state and you can assess the dose fairly. That is an argument for not going faster. It is not an argument against going slower.

That distinction has done more work for me than anything else in this category.

Escalating before steady state means you are judging a dose you have not yet fully experienced. That is the whole argument against compressing the schedule and it is a good one.

Narrowing post #3, because the general version has more than one answer.

If symptoms reset at each step, that is the expected pattern rather than a sign that the previous adaptation was imaginary. Every dose increase is a new exposure.

Steady state means the plasma concentration is stable from dose to dose. That happens around 4 to 5 half-lives. Before that, the concentration is rising with each dose. Escalating before steady state means escalating on incomplete information about the dose you are on.

That is all I can say without guessing.