The first big problem with .22 LR is penetration. Especially when fired from a short barreled pistol. Even if you hit the right spot, it might not penetrate deep enough to do the damage you need it to.
The second big problem is reliable feeding in an automatic. Rimmed cartridges can get stuck on each other easily and cause "rim lock". Which can cause a malfunction.
Heavy clothing, wierd angles, large body can cause a failure to stop with any caliber, but with the .22 LR at the low velocity it will achieve when fired out of a handgun increases those chances even further.
Really, when you are using a .22 LR, you are making a gamble that whoever you are shooting doesn't want to get shot, and the threat of or actually being shot will stop the agression. (That is probably a pretty good gamble honestly)
That being said, if that is all you can afford/manage, then it is better than cussing.