Follow-up: The lowest dose that does anything: is that a real question? posts 61–76

Same experience here, different supplier, so it is at least not unique to one of them.

Post #59 answers the question as asked. The question underneath it is different.

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.

I have deliberately not rounded that, because the rounding is where the argument starts.

Splitting a weekly dose in two: the pharmacokinetic argument against is that you want the benefit of long half-life, which gives a slowly changing plasma level from a weekly dosing schedule. Splitting it flattens the curve further but loses the convenience of once-weekly dosing. The trade-off is convenience versus a slightly flatter concentration curve.

The version of lowest dose 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.

Nothing here is medical advice, and a titration question is one of the few where a prescriber can genuinely answer in a minute what a thread will take a week to circle.

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.

The rule of thumb is fine; the edge cases are where it earns its keep.

Worth separating two things that post #63 runs together.

Agreed on lowest dose, with one qualification that I think matters. The reasoning holds for the case as described. Change the starting assumption and it does not, and the starting assumption is the part nobody states.

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.

I had written a reply contradicting post #67 and deleted it. Here is what survived.

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.

Fine by me. I had wanted a stronger conclusion and there is not one available.

This is the first time the answer has come with its own limits attached. Appreciated.

Going back down a step is not a failure and the trials allowed it. Several protocols permitted a return to the previous dose for tolerability and then a second attempt at the step.

That is the shape of it. The detail is where I would expect to be corrected.

Writing down the date, the dose and the site each week takes fifteen seconds and is the single most useful record anyone here keeps. Memory reconstructs a titration history that never happened.

Not a conclusion. A place to stand while looking for one.

Post #72 describes the usual case. This is about the unusual one.

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.

If anyone has run this properly I would rather read that than my own guess.