One one of my sites we would get anywhere from 150-250 spam comments a day, on a regular basis. Akismet would toss most of the into the spam bucket, but I hadn't realized that my comments meta table was getting out of control because of how much info about comments Akismet was "tracking".

The helper plugin I started using was WP Conditional Captcha, because it came with a control to disable Akismet's comment history instead of having to fiddle with admin.php as one thread on wp.org suggested. I did have to manually delete all that historical data from my database, approx 80Mb worth of useless comment meta cluttering up the mysql database ever since they'd added that "feature" to Akismet, and the history cleanup they added in didn't (doesn't?) work.

I still get about 20-40 comments a day or so that I have to delete out of spam, maybe 5-10 per week that I have to manually mark as spam, but my database is still normal sized (for how old the site is), and my comments are mostly clean :)