Two enzymes act on one prescription, and one of them turns the first drug into the second. The guideline behind it was written for depression doses, and most people who take it here are taking a tenth as much for migraine.
Amitriptyline is one of the oldest and most used migraine preventives, and its handling depends on two enzymes at once. CYP2C19 converts amitriptyline into nortriptyline, which is itself an active drug, and CYP2D6 clears both. A poor metaboliser at CYP2D6 accumulates more drug than intended and is more likely to stop because of dry mouth, sedation or a racing heart; an ultrarapid metaboliser may never reach a useful level. CPIC recommends avoiding the drug or halving the starting dose at both extremes, and considering a therapeutic drug level if it is used anyway. One caveat matters more here than the recommendation does: the guideline was written for the doses used to treat depression, and migraine prophylaxis typically uses a fraction of them, so how much of this carries over to a 10 mg bedtime dose is genuinely not settled. This is a prescriber’s decision, not something to act on from a raw data file.
Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.