It would be a Starlight/Trixie episode. it would start out with Starlight asking Trixie about her family, and Trixie shows her a photo of her and her sisters, Screwloose and Shoeshine, who are twins. Starlight realizes that she only ever saw Shoeshine in ponyville, and asks about Screwloose. Trixie then takes her to the Asylum to meet Screwloose. Starlight and Trixie then decide to try to get her out of the Asylum. They do various things to help out Screwloose, and learn other patient’s stories alongside that, including the story of May Day, a pony who got teased so much for being a blank flank even as an adult that it drove her crazy, Fallen Sky, a pony who admitted himself to the mental hospital due to issues with schizophrenia, and Volcano, a pony who is absolute nuts. The trio eventually get Screwloose out, and even Fallen Sky and, with some effort, Volcano.

The main character would be fluttershy. The plot would be: Spike, Rainbow Dash, and Pinkie Pie all go into fluttershy’s shed looking for the elements of harmony (because Discord has returned and he’s evil again) but discover many dead/skinned animals all around the shed (with an appearance from derpy, who has been turned into a toaster cosy). Rainbow dash is captured by fluttershy and, after a short song, fluttershy kills her with a chainsaw. She is shortly taken in by the police and brought to the mental asylum.

@Mayojar77  
Bleh.

@The Chaos Hunger  
No, her becoming good happened.

@Mayojar77  
And Luna was truly evil all along and was destroyed when she returned and tried to take over the world again.

Trixie goes crazy after her loss with twilight again, a little too crazy…

Twilight was never Celestia’s personal student. It was all a dream she had while in a coma. She really was just a sickly Unicorn Noble filly. There were only ever five Elements of Harmony. Celestia doesn’t even take on students anyway.

Trixie visits her sister Screwloose in the psych ward.
 
She smuggles in some dog treats, just for her.

PLEASE not a male Screw Loose… please?

PLEASE not a male Screw Loose… please?

Either Twilight gets stressed enough that she can’t be left unattended, or Fluttershy’s social anxiety gets too harsh for her the handle the outside world.

@PonyPon  
Everypony, even AJ, finds even crazier versions of themselves, who are on the road to recovery.  
There’s a pony in a straightjacket and hockey mask, with a lock cutie mark.  
Increasingly frazzled versions of background ponies are in group sessions.

It turns out that Twilight never solved the whole “Switched Destinies” thing and the strain of trying caused her to completely snap.  
Everything from just before “A True, True Friend” onwards has just been her friend imagining what would have happened if she had.
 
Meanwhile, the other five, having grown accustomed to their “new destinies” take the time to visit her and play along with her delusions of Princesshood and visiting a world filled with shaved apes.

I just checked if Daemon had released a new chapter of Asylum and then I come here and see this. You scare me.

They have to break Screwloose out of an asylum at Scootalo’s behest (because she’s her mom).  
They meet all the nutjobs Equestria doesn’t have room for, and even find Discord making friends/receiving therapy.  
The lesson is that modern medicine is not evil, and they leave her there to get the care she needs.
 
Will add more to that if I think of any.

Twilight Sparkle, Rainbow Dash, Applejack, Rarity, Pinkie Pie, and Background Ponies #427-#470.  
It’s about asylum stuff.  
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Before anyone asks, Screwy Louie was the name I came up with for R63’d Screw Loose.