The opening post is right about the mechanism and I think understates the practical bit. What I would want before treating micro-titration as settled: the method, the sample, and whether anyone tried to find the opposite result. Two of the three are usually missing.
Micro-titration: a disputed topic, argued properly Writing it up because I had to work it out twice and would rather nobody else did.
Two things I would like separated before anyone answers on micro-titration, 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 opening post is right about the mechanism and I think understates the practical bit.
What I would want before treating micro-titration as settled: the method, the sample, and whether anyone tried to find the opposite result. Two of the three are usually missing.
The reason micro-titration keeps being re-asked is that the answer is conditional and people quote it without the condition. It is not that the answer is unknown.
Post #5 answers the question as asked. The question underneath it is different.
Taking micro-titration seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.
The starting dose in most of these programmes is a tolerance step and produces little effect by design. Judging the compound at the starting dose is judging the wrong thing.
Small correction to my own earlier position on micro-titration. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.
Worth separating micro-titration as a question about the compound from micro-titration as a question about the documentation. They get answered by different people and only one of them is answerable here.
Micro-titration: the concept of increments smaller than the labelled steps. It has no evidence base from trials but is described by some people. The downside is that very small increments are hard to measure accurately with a syringe.
The honest answer is that it depends, and here is what it depends on.
Right — I had this wrong and I am glad to have read it before it mattered.
Coming back to post #13, 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.
Take the reasoning and check the arithmetic; I do not always get it right.
Adding a null result on micro-titration. I looked, carefully, and found nothing, and null results deserve posting precisely because they never are.
This follows post #14 rather than contradicting it.
A titration plan written down in advance is easier to stick to and easier to abandon deliberately. An improvised one becomes a series of decisions made on the worst day of each week.
The variance between people here is larger than the effect being discussed.
Where the micro-titration reasoning breaks down for me is the step from the group result to the individual case. That step is almost never argued for.
Micro-titration looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.
On post #16 — agreed on the reasoning, with one qualification.
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.
Worth separating two things that post #17 runs together.
I would keep micro-titration and the decision it usually gets used for separate in this thread. They are related and they are not the same question, and merging them is why the last one went badly.
Agreed on all of that, and I have nothing to add to it.
Holding a dose indefinitely: the trials did not study indefinite holding at a non-maximum dose. The trials escalated to a target and then held that. What happens if you stay at an intermediate dose for years is not formally studied and extrapolation is the best available reasoning.
No disagreement from me. Posting only so the question does not look ignored.
Coming back to post #26, because the follow-up matters more than the original answer.
Micro-titration is worth one more sentence than it usually gets, and the sentence is the one about how the number was arrived at.
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.
Not the whole picture, but the part of it I can speak to.
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.