Maintenance dosing: what is licensed, what is practised, and what is evidenced
Every withdrawal trial compared full dose against nothing. The clinically interesting comparison — full dose against a reduced one — has not been randomised.
Maintenance
Page 5 of 9 of this archive, newest first.
Do you need the top of the ladder?
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
When a symptom is information and when it is noise
The practice is near-universal, clinically sensible, and supported by observational data rather than randomised comparison. We say which is which.
Not everybody regains at the same rate, and nobody knows why
What returns, in what order, and how much of the benefit survives.
The eighteenth month, and the conversation that should have happened in the third
The dose-response curve in this class flattens near its top. That has direct consequences for whether the final rung is worth climbing.
Holding a dose is a decision, not a failure
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
The restart nobody plans for
We work through the residual-exposure table so the decision can be made from numbers rather than from feel.
Side effects, cost, supply, target: four reasons with four trajectories
Real-world persistence figures, with their definitions stated, because the definitions are doing most of the work.
Why people actually stop, in the order they actually stop
Why the reason for stopping changes what happens afterwards.
What happens when the drug is taken away: three randomised answers
What was withdrawn, from whom, after how long, and what was measured afterwards.
Stepping down is part of titration
Every major phase 3 protocol in this class allowed escalation to be delayed for tolerability. Almost no product label explains the mechanics of doing so.
Do you need the top of the ladder?
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
Maximum tolerated is not maximum approved
A plateau at an intermediate dose and a plateau at the maximum dose look identical from the outside and mean different things.
What a month without the drug does to tolerability
The convention — resume lower, re-escalate — is not caution. It follows directly from the elimination half-life.
The steps get smaller as the ladder gets higher, and that is deliberate
What the published pharmacokinetics permit, what the labels state, and where the two diverge.
The dose you were told to reach and the dose you will actually stay on
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
Seasonal use, holiday use, and the honest state of the evidence
The schedules in circulation, described accurately, with their evidentiary status attached.
Holding a dose is a decision, not a failure
Nausea and gastric delay attenuate over weeks at an unchanged dose. That single physiological fact is the entire justification for holding.
The lowest effective dose is a real concept with almost no data behind it
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
The arithmetic of a step: what doubling a dose actually asks of you
What the published pharmacokinetics permit, what the labels state, and where the two diverge.