2 ideas from testing I have done.
1) GW Guardian, although labelled as GroupWise Guardian, this is a MS server and Exchange compliant system, VERY ROBUST!!! VERY expensive!!
2) GWAVA, again designd for GroupWise but I believe this is also available for Exchange and Lotus Notes. This is a FANTASTIC solution and by far he most powerful and robust scanning system I have ever used. Both of these products scan BEFORE the mail is in the server or delivered to the client. They incorporate your existing AV solution and are very resourceful. GWAVA took a little fiddling, as fo most, but their new interface allows it to scan YOUR mail and create HAM/APM lists based on a heuristic scamn of what you want and what you don't, this is VERY accurate and with a client receiving nearly 1500 emails per week, I managed to get it down to 0-1 false positive trapped each week with NO spam hitting the desktops. Less expensive than Guardian too.
GW Guardian : http://www.gwtools.com/products.cfm?doc_id=307&p=16&CFID=109003&CFTOKEN=12628667
GWAVA: http://www.gwava.com (their support is pretty good too)