I just lay the phone down, wait until they have realised nobody is responding, then hang up. I don't get many, though - 7 or 8 a day would drive me nuts - we registered with TPS ages ago and it does seem to work for us. (I wonder if it makes a difference where you live?)
I work in a call centre - holiday cottage bookings, mostly incoming, no cold calling at all, occasional outgoing calls to customers with problems, property owners etc. We have thousands of different lines and numbers, incoming calls are allocated at random, and I had a very strange one this week; as soon as I answered the woman shrieked at me "where did you get my number?" It transpired that her number is ex-d; she had had a call from one of our lines, hung up as soon as the person spoke to her but without asking them how they got the number or why they were ringing which would have been intelligent (but obviously not for someone with severe paranoia), got the number from 1471 - it's an 0870 number so you'd think she'd realise she was wasting her time - and rung straight back, and I was the lucky one she connected to.
She wouldn't have it that I hadn't a clue who had rung, or why, or how they came to call her number - I suggested a wrong number but apparently in her mind that's impossible if you're ex-d - she threatened, in a triumphant way, to report us to the police, FFS. In the end I transferred her to the switchboard, not realising it was 6pm and receptionist was long gone; I don't know if she tried again.
The sad thing is it's entirely possible that someone at her house had booked a holiday as a surprise for her - maybe because she is obviously completely over-wrought! - and someone had rung in connection with that. God knows what the outcome was though.