I have a huge database, too and had to start multiple instances since similarity gets unstable with cache sizes between 50k and 100k entries. Each of the instances work on part of the data with its own smaller cache file. To achieve that you have to copy (or hard link) the similarity files to different directories (e.g. A_K and L_Z). With the /portable switch each of the directories gets its own configuration, cache and license files. After starting the instances you have to enter the license data for each of them and you will get several premium versions.
I would recommend to start the next instance not before the cache file has been read by the previous one, since concurrent HD access really slows down both instances because of excessive head movement (but not for SSD). When the cache file has been read, CPU usage dominates disk usage. You will only get a small increase in throughput since sometimes one instance can use more CPU time while the other waits for disk I/O to complete.