Since steady state keeps coming up, it should probably be a maintained page rather than a recurring thread. I am happy to draft it if someone with more direct experience will review it.
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Practice · Dosing & titration · continued
[2026 update] What steady state means for the decision to escalate posts 31–60
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
g.ibarra, post #10: I changed my mind about steady state after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens. Go to post
Split dosing within a week is sometimes proposed to smooth tolerability. With a week-long half-life the concentration is already smooth, so what it would change is the timing of the peak rather than its existence.
If this contradicts something upthread, the upthread version may well be the better one.
Sensible. I would want the same detail before I acted on it either.
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ppm_error, post #7: 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. Go to post
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.
s.oyelaran, post #15: 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. Go to post
Post #32 describes the usual case. This is about the unusual one.
Checked the steady state claim against the primary source this morning. It survives, with a narrower scope than the version quoted here. Posting the narrower scope.
k.brandl_de, post #33: Sensible. I would want the same detail before I acted on it either. Go to post
The arithmetic in post #38 is right; the assumption feeding it is the part to check.
Steady state came up in a thread eighteen months ago and was answered well. I cannot find it, which is itself the problem, so here is the reconstruction.
Answering the question post #36 raises rather than the one it answers.
A note on how steady state gets discussed rather than on steady state itself: the confident posts get the replies and the careful ones get ignored, and the careful ones have been right more often.
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Building on post #40 rather than restating 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.
It is worth stating the boring hypothesis before the interesting one.
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s.oyelaran, post #15: 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. Go to post
Everything in post #42 holds. The case it does not cover is the one I have.
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".
a.pereira, post #6: Confirming post #3 from a second method, which matters more than confirming it from a second person. The most useful thing anyone has posted about steady state in this category was a table of what had been measured and by whom. That is what I would want again. Go to post
I have been on both sides of the steady state argument in this category within eighteen months, which should tell you how strong the evidence for either side is.
Taking post #45 at face value and following it one step further.
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.
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c.marchetti, post #22: Post #19 is right about the mechanism and I think understates the practical bit. For anyone finding this later: the short answer on steady state is that it depends on one thing, and the rest of the thread is people identifying which thing. Go to post
Whatever the answer on steady state turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, invite the correction.
Reaching a dose and staying there for a year: the question of whether a stable dose remains effective over years is mostly answered by the withdrawal trials and by real-world reports. The dose does not seem to stop working, but the longest trials are not indefinitely long.
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Seconded. It reads as careful rather than confident, which is the right register.
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Building on post #49 rather than restating 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.
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Collapsed as off-topic by two members at trust level 3 or above
What would change my mind on steady state is a second dataset collected by someone with no stake in the first. Until then I hold it loosely and I would rather say so than pretend to more.
On steady state, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.
If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.
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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.
This is the sort of thing the wiki should carry and currently does not.
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j.marchetti, post #51: Building on post #49 rather than restating 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. Go to post
Taking post #53 at face value and following it one step further.
A request rather than an answer: could whoever has the primary source for steady state post it? I have seen the claim three times this month and each version had lost a qualifier.
s.cardoso, post #9: Second this, and I would have said it less carefully. Go to post
Post #54 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.
Speaking only to steady state as I have actually seen it, rather than as it is usually described: the effect is real, it is smaller than the thread suggests, and the variance between people is larger than the effect.
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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.
The short version is the first sentence; the rest is why.
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I keep a log for steady state specifically because my memory of it turned out to be systematically wrong in one direction. Six weeks of notes cost nothing and settled it.
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