Some might argue that one of the more capable .22 rimfire cartridges could be your carry gun.
Might have to work the double - triple tap more aggressively.
-and-
The problem is that no .22LR ammo I've ever found is inherently reliable enough to depend on for SD. WAY too many misfires, and that's before we even get into feeding and extraction problems (remember that the .22 RF cartridge was never designed to work in semiauto actions). It's actually amazing that they work as well as they do, all things considered--but it's still not reliable enough to suit me.
FWIW, the most reliable .22LR ammo I've ever found was CCI MiniMags, and I wouldn't even trust them.
If for some reason I absolutely HAD to rely on a .22LR for SD, it would have to be in something that doesn't rely on flawless feeding, and that wouldn't be stopped by a misfire. That narrows things down to a revolver--preferably a DA carrying 8, 9, or 10 shots.
Just my opinion, worth exactly what you paid for it.
Indeed, the use of the .22LR as a defensive weapon -specifically in the context of those with compromised physical capabilities (i.e. insufficient grip strength to manage recoil typical of modern defensive calibers) has been something that's been highly contested in the industry.
Overall, the main concern that I personally align with is the .22LR's lack of consistency in ignition, as well as the oftentimes fickle nature of .22LR autoloaders (be it handgun or rifle).
The former is often improved with the better manufacturers, but in my limited personal experience, it's still less reliable than even "range-fodder"-grade centerfire 9x19, .38 Special, .357 SIG, .40 S&W, or .45 ACP. That said, there also remains a possible compromise between centerfire and .22LR in the .22 WMR cartridge which, at least in terms of penetration (in calibrated ballistic gelatin), measures up to modern defensive caliber standards (expansion, however, is lacking).
The hardware issue is in my view probably the simpler of the two to fix: as
@Snake45 and
@HansGruber noted, one's odds can be improved significantly with weapon selection, specifically in terms of the flyweight snub revolver. Greg Ellifritz as well as other SMEs also suggest that for those who are able, to entertain the possibility of carrying *_two_* of these firearms, versus carrying loose reloads.
And it is really here that we come to the crux of the discussion - whether if "compromised" defenses are somehow worth the effort/expense. Here I found myself agreeing with the likes of Craig Douglas (ShivWorks - who lent his expertise on this now nearly 10-year-old M4C.net thread:
https://www.m4carbine.net/showthrea...e-22-LR-handgun-for-age-physically-restricted) - that "a gun" is better than no gun.