I had some rather serious carpel tunnel in my right hand and after the operation had problems holding and controlling the pick when doing fast melody style flat picking. A while back I happened to try the Dunlop Big Stubby flat pick. It's made of 3mm thick Lexon and has a depression on each side. I hold it with the first finger curled and the other fingers relaxed. The depressions are placed between the end joint of the thumb and the last joint on the first finger. It seemed a bit awkward due to the thickness, however, after using it for a while it's my favorite pick. The depressions keep the pick where it belongs.   

Cap't Bob