Follow-up: Where the four-week escalation interval comes from, and what it is not posts 91–120
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
The strongest argument against my own position on four-week escalation interval, stated as well as I can state it, since nobody else has yet.
This follows post #94 rather than contradicting it.
Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.
That matches what I have seen, for whatever a single anecdote is worth.
If you are stepping up mainly because the schedule says so rather than because the current dose has stopped doing what you wanted, that is worth noticing before rather than afterwards.
I would put the burden of proof on the interesting explanation, not the dull one.
A note on scope: what I am saying about four-week escalation interval applies to the case in the first post and I would not extend it further without checking.
Four-week escalation interval is worth one more sentence than it usually gets, and the sentence is the one about how the number was arrived at.
Everything in post #99 holds. The case it does not cover is the one I have.
Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.
It took me longer than it should have to see that.
Fair, and the limits you put on it are the part I will remember.
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.
Post #104 answers the question as asked. The question underneath it is different.
An update on my earlier four-week escalation interval post: the pattern held for another six weeks and then stopped, which I did not predict and cannot explain.
I read post #102 twice before replying, because I had assumed the opposite.
What I would tell a new member reading about four-week escalation interval for the first time: the confident posts are not the reliable ones, and the reliable ones are longer.
The four-week step is a trial convention, not a pharmacological constant. It is roughly four half-lives for a week-long half-life, which is the interval at which you are assessing a stable concentration rather than a rising one.
Post #108 is right about the mechanism and I think understates the practical bit.
Two questions I would want answered before drawing anything from the four-week escalation interval data above: how were the cases selected, and what happened to the ones that dropped out.
Post #109 and I disagree about the size of the effect, not about the direction.
Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.
Scoping that to what I have actually seen rather than what I have read.
Practical experience of four-week escalation interval, offered as one case with the conditions stated, not as a general finding. Conditions first, because they are what make it interpretable.
The arithmetic of an intermediate dose: if the label says 1.0 mg and 2.0 mg, a dose strictly between them is off-label by definition. Some people compute it anyway. The reasoning is pharmacological — e.g., "I will split the difference between steps" — but it is reasoning from theory, not from evidence.
That is consistent with mine, for whatever one more account is worth.
Building on post #113 rather than restating it.
Four-week escalation interval was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.
Concentration and dose get conflated constantly in this subcategory. Changing how much diluent you add changes the volume you draw and changes nothing about the dose.
That is all the detail I have. Someone else will have more.
Collapsed as off-topic by two members at trust level 3 or above
Stepping down deliberately: the withdrawal trials show that stopping is followed by regain. The step-down literature is thinner. The conservative assumption is that stepping down is followed by some regain, with the magnitude unknown.
Post #117 is the version of this I will quote in future. One addition.
I would be cautious about generalising from the four-week escalation interval example above. It is a good example. It is one example.