The 60-year-old actress made the surprising revelation as she sat down with chat show host Queen Latifah to promote new film Nightcrawler with her co-star Jake Gyllenhaal.
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Rene Russo has revealed her battle with bipolar disorder
Both guests were asked about something they had to "push through" in their lives, and Rene decided to open up about her struggle with the disorder.
"My mum said my whole childhood… was stop and go," the actress said of the illness, which can see dramatic swings in both mood and energy levels.
"I literally crashed, hit a wall and couldn't get out of bed," Rene added of her decision to start taking medication. "I thought it was depression, but if you take antidepressants it speeds you up more.
Rene Russo with her Nightcrawler co-star Jake Gyllenhaal
"I haven't shared this," she continued. "I have friend who don't want to go on medication, and they are suffering."
Clearly moved by her bravery and honesty, Queen Latifah told the star, "Thank you so much for sharing that. That can really help some people."
The episode featuring Rene and Jake is set to air on 30 October.