You have to ask what is "self defense". I know that the situations that I have had here in my house/garden/neighborhood, a round nose 22LR would not just make a difference for the better, but the required difference.
If I were in an actual gun fight, I might just want something else (probably a fast handling rifle). Sometimes self defense is a matter of changing someones mind/attitude. A lead round nose in 38/three-fifty-etc is more than the candidate IMHO.
Have you ever noticed that in conflict of any kind, the one who intimidates most wins? It's the aggressors overbearing presence that gets them the advantage. Not what a bullet is made of. That is why hijackers were able to fly planes into skyscrapers... because they intimidated and terrified people. The folks who lost and died did not get cut with a box cutter. And I mean that most respectfully.
It's all in the mind. But carry what you feel confident with. There are times that having even a Leatherman have given me the confidence to walk right in to the shadow of the valley.