.25 is totally insufficient. I SAW a guy shoot himself in the TEMPLE with the muzzle against the skin. The round hit no bone. It went through the temple, cut the right optic nerve and exited the left eyeball. It also blew out the sinuses. The guy is blind for life, but he got up and ran around until I got him down and compressed the wound until the ambulance arrived. The guy was being stupid with a firearm and shot himself.
Doctor said that he could have easily died had the round been bigger or smaller. A .22 could have been lethal and a 9mm too, but the .25 was so underpowered it couldn't penetrate the bag around the brain, instead it went around it. There was a burn mark on it though and it bruised some things up, but otherwise was unable to get through to the brain. Lucky, lucky guy.
I've also heard of .25's bouncing off the head. Seriously. When I saw this guy get shot I thought this was what happened at first, there was no blood and he was holding his head like he had a bad headache (and wasn't dead from a headshot!). But when he moved his hand from his temple, blood shot out three feet under pressure for a half second and I knew I needed to call 911.
I wouldn't depend on .25 for defense. This was an FMJ round and it couldn't penetrate the brain from the temple? What, are you going to shoot beween the tear duct and the eyeball for an unobstructed head on shot?
With all these new mini pieces out there, get something else. There are .45ACP titanium derringers, mini 9's, tiny .380's, and I have a scandium .357. I'd like to have the 2 shot .45ACP derringer in titanium, but they are going to have to come down from the $950 cloud they are occupying at the moment, way on down to the $400 bill of sale I'm willing to sign. That little thing is great for the pocket as a backup or whatever, only 5/8" and smaller than a cell phone!
If you have your heart on a mini auto, a real mini, the .22 would probably be a better choice. It is a fairly high pressure and velocity round, highly efficient for its size. A magnum would be better, and a 9mm or larger centerfire better still.