In 2002, Laura Spencer was committed to Shadybrook because she thought that she killed Rick Webber after hitting him with a candlestick. Shadybrook becomes the permanent home to her after her mental breakdown and slip into catatonia. In 2006, Laura temporarily awakes and shares a tearful reunion with her family before slipping back into catatonia. Later in 2008, Laura awakes for good and moves to Paris, after spending almost 7 years at Shadybrook.
In 2005, Carly Corinthos became jealous and obsessed with Reese Marshall's role in Sonny and Michael Corinthos' life. Soon she had a complete breakdown and ends up being institutionalized after remembering Reese's true identity from when she was a teen. She later stands on the building's ledge, threatening to jump after hearing Sonny tell Jason Morgan that her life is over. Carly later recovers and escapes months after.
Elizabeth Webber was committed to Shadybrook in 2010, after having an affair with Nikolas Cassadine, which sent her down a dark path. She later checked herself into Shadybrook in 2011, hoping Lucky Spencer would come back to her out of sympathy.
In May 2012, Kate Howard was checked into Shadybrook to seek treatment for dissociative identity disorder. Her alternate personality Connie wreaked havoc in Sonny and Kate's lives until Kate was arrested and later committed. After Kate was integrated in 2013 she chose to use her birth name Connie Falconeri.
In January 2015, Heather Webber took residence at Shadybrook, where she befriended Nina Reeves. Heather planned to enact revenge on her son Franco Baldwin through Nina and attempted to inject her with LSD however Franco arrived in time to prevent this from happening.
In August 2015, Nina checked herself into Shadybrook and "befriended" a catatonic patient whom she called Heidi. Nina was later removed from the facility when she was arrested for Silas Clay's murder.
On November 1, 2019, Ava Jerome checked herself into Shadybrook with Laura and Julian’s help after having a mental breakdown caused by alcohol and Nikolas' return.
On March 1, 2021, Franco Baldwin plans to check himself into Shadybrook after almost attacking his stepson Cameron, due to the effects of his re-emerged brain tumor. He spends the night in a Metro Court suite and plans to head to Shadybrook the next day but instead he discovers Peter August was behind Drew’s kidnapping. Franco knocks out Peter and holds him hostage in his Art Studio and Loft. On March 9, Franco is shot and killed after struggling with Peter for a gun so he never makes it to Shadybrook.