This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
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.
A modest claim, modestly supported.
Agreed, and I will stop repeating the version of this I had been repeating.
Adding a reference point for four-week escalation interval. Mine is a single case, collected without controls, and I am posting the method alongside it so it can be discounted appropriately.
I read post #35 twice before replying, because I had assumed the opposite.
Holding at a dose that is working is a legitimate position and it is not what the trial protocols did. The protocols escalated to a target because they were measuring the target dose, not finding each person's minimum.
Taking post #36 at face value and following it one step further.
Practical answer on four-week escalation interval, since the theoretical one is upthread: do the simplest check first, write down the result, and only then decide whether the complicated explanation is needed. It usually is not.
Titrating on tolerability rather than on the calendar: some people escalate when they tolerate a dose well, others escalate on the prescribed schedule regardless. The published trials used a calendar-based schedule. Tolerability-based escalation has no formal evidence base but is not uncommon in practice.
Written from notes rather than memory, which is why the numbers are specific.
Adding the measurement that post #36 says would settle it.
The version of four-week escalation interval that circulates here is a simplification of a simplification. It is not wrong, but it has lost the conditions under which it holds, and those conditions are where the interesting cases live.
I have no financial interest in anything named in this thread and I want to say so before I comment on four-week escalation interval, because it is the sort of subject where it matters.
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.
It is the kind of thing that is obvious once and never again.
Picking up post #39: that is the part I would want checked first.
Careful with the language on four-week escalation interval. "Not detected" and "not present" are different findings and the first is a statement about the method.
Four-week escalation interval: I have looked for the primary source twice and failed twice. Either it does not exist or it is somewhere I do not know to look, and I would like to know which.
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.
Where I would look next, rather than where I would stop.
The thing about four-week escalation interval that took me longest to accept is that a plausible mechanism is not evidence of an effect. It is a reason to look, not a result.
Following this. I have the same question and no better information than the first post.
I read post #43 twice before replying, because I had assumed the opposite.
Adding a small correction to the four-week escalation interval summary above rather than a disagreement with it. The substance holds; one of the figures is out by a factor that matters.
Post #47 and I disagree about the size of the effect, not about the direction.
An honest declaration on four-week escalation interval: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.
Having read the whole four-week escalation interval thread before replying: the question in the first post has not actually been answered yet, and three of us have answered a nearby one instead.
Post #50 answers the question as asked. The question underneath it is different.
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.
The right answer here may simply be that it has not been measured.
There is no published evidence about slower escalation because nobody studied it. That means the trials support not going faster and are silent on going slower, which is a different claim from "slower is fine".
The short answer was in the first line; everything after is the working.
Before the thread moves on from four-week escalation interval — what is the sample size behind the claim? I am not being difficult; I have seen the same figure quoted from an n of four and from an n of four hundred.
Worth separating two things that post #52 runs together.
Adding the boring version of four-week escalation interval, because the interesting version keeps getting posted and the boring one is usually right.
Check the ordinary explanations, in order, and stop when one of them accounts for what you are seeing. Most of the time the second one does.
Adding thanks rather than a view. I do not have a view worth the space.
Coming back to post #52, because the follow-up matters more than the original answer.
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.
I am describing what is, rather than arguing for what should be.
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.
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.
I had written a reply contradicting post #56 and deleted it. Here is what survived.
The question underneath four-week escalation interval is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.
Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.