Reaching a dose and staying there for a year: a longitudinal note — does this still hold? posts 31–40

I had written a reply contradicting post #29 and deleted it. Here is what survived.

Dose and effect are not linear across the studied range for every compound in this class. Assuming a doubled dose gives a doubled effect is the reasoning error behind most disappointment.

The strength of my opinion here exceeds the strength of my evidence.

Nothing to add on the substance. Thank you for taking the question at face value.

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.

Coming back to post #33, because the follow-up matters more than the original answer.

Escalating before steady state means you are judging a dose you have not yet fully experienced. That is the whole argument against compressing the schedule and it is a good one.

The part I am sure of is shorter than the part I have written.

If symptoms reset at each step, that is the expected pattern rather than a sign that the previous adaptation was imaginary. Every dose increase is a new exposure.

A missed dose in a weekly schedule is not a trough to chase. With a week-long half-life you are perturbing a slowly moving average, and the labelling for licensed products in this class says take it if the next dose is far enough away and skip it otherwise.

Flagging that the sources on this are thinner than the confidence in the thread suggests.

This follows post #37 rather than contradicting it.

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.

The number is defensible. The precision I gave it is not.

Grateful for the specificity. Vague answers to this question are what sent me looking.

Building on post #37 rather than restating it.

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.