5mg → 10mg → 15mg titration — clinical guidance and real-world data

Dr.Martinez said:

The trials generally allowed a step to be held or reduced and then retried, and people who did that mostly arrived at the same place a few weeks…

Agreeing with Dr.Martinez, and the qualification matters more than the agreement. Four weeks is the pharmacokinetics, not caution. With a one-week half-life you need four to five half-lives to reach steady state, so at two weeks you are dosing on top of a concentration that has not finished rising. Escalating then stacks exposure and you get the side-effect burden of the higher dose before you have seen the benefit of the current one.

Dr.Martinez said:

The trials generally allowed a step to be held or reduced and then retried, and people who did that mostly arrived at the same place a few weeks…

I disagree that the ladder is purely tolerability. The maintenance and regain data cluster at the top doses, so a ladder abandoned halfway leaves you outside the evidence base for the part that matters most — keeping it off.

That is the short version; the long version is somebody else's post.

Short answer first, then the reasoning. Holding longer is the underrated move. A step that is uncomfortable at week two is frequently comfortable at week six with no change in dose, because the gastric-emptying component tachyphylaxes while the appetite effect persists. Escalating at week two throws that adaptation away.

pete_manc_UK said:

Four weeks is the pharmacokinetics, not caution.

Agreed, and subgroup analyses deserve particular suspicion. With enough subgroups something is significant by chance, and pre-registered subgroups are a different animal from ones found afterwards.