You are probably using server-stored profiles for your users. This can slow the software down radically as Password Safe needs to read and write to the configuration file continuously. For this reason, the configuration file for Password Safe should always be located locally.
In the case of a server-stored profile, however, all the profile data is managed by Microsoft on the server and kept synchronized automatically, but this is extremely slow.
It is best that you specify that the Password Safe configuration file is saved locally in a different folder.