I've heard folks complain it gets slow with very large or old mailboxes. One reason that happens is that they need to be compacted, another is that the sqlites need to be vacuumed.

So, twice a year I compact my mailboxes, and I put a sqlite command loop to vacuum in my main cleanup script. Which I run maybe once a month.

Yes, strictly speaking I shouldn't need to do this, but my tbird install has been running happily for decades now.