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Katie Holmes, Matt Lauer, Tom Cruise

Getty Images; NBC; WireImage

Matt Lauer had no choice but to address the elephant in the room.

On Tuesday, the Today co-host interviewed Katie Holmes, who plays a poet struggling with bipolar disorder in director/screenwriter Paul Dalio's film Touched With Fire. Given his tense interview in 2005 with her ex-husband Tom Cruise, in which they debated the merits of pharmaceutical drugs, Lauer asked Holmes how she felt taking on such a dramatic role. "This was a huge challenge and one that I felt pressured to create an authentic character," Holmes said, "because so many people do suffer and I wanted to bring a realistic portrayal to the role."

"But you can't just read about something like that," Lauer told Holmes, who divorced Cruise in the summer of 2012. "Have you had people close to you—family, friends—who've had this condition?"

"You know, I have not had many experiences, no, with knowing people with this, but when I met with Paul, our director, he told me that this was his story and shed more light on what he's gone through and why we were making this movie and how important it is to him," Holmes said of doing her research for the role. "This movie, the cast, the crew—everybody was so inspired by him that there was just this energy on set to create something very authentic and very real."

Lauer said the movie asks viewers an important question: "Is it beneficial to treat these people with drugs?" He then referred to his now infamous interview with Cruise, reminding Holmes, "You and I both remember a heated discussion I got into on that subject here in this studio. How do you think the movie comes down on that? Where do you think it leads the viewer?"

Holmes didn't answer outright. Instead, she praised Dalio for shedding a light on people who are struggling with bipolar disorder. "What I think that our director did a wonderful job with is this movie kind of just shows, 'This is it.' These are these two characters in love story—which he's saying is kind of its own mania, to fall in love," the actress said. "But he puts the question out there for the audience to make that decision."

"They can live their lives when they're on the medication, but they don't feel like they're living full lives on the medication, which is a very difficult balance," Lauer said. "Right," Holmes said.

Cruise had a different take when he appeared on Today in 2005.

As a Scientologist, Cruise doesn't believe in the use of pharmaceutical drugs or therapy of any kind. At one point, Cruise called Lauer "glib" and argued the co-host didn't know what he was talking about. Lauer had mentioned Brooke Shields, whom Cruise had criticized for promoting medication to deal with postpartum depression. After the actor started a detailed discussion of the use of the prescription drug Ritalin, Lauer told the War of the World star, "It's very impressive to listen to you, because clearly, you've done the homework. And you know the subject."

Cruise fired back, "And you should."

The actor also told Lauer, "You don't know the history of psychiatry. I do."

Lauer told Cruise he had known people who had been helped by psychiatric drugs, including Shields. As a result, Cruise accused Lauer of advocating the use of Ritalin. "I'm not prescribing Ritalin, Tom, and I'm not asking anyone else to do it," Lauer assured him. Cruise wanted to make himself clear before the interview ended. "I've never agreed with psychiatry, ever," he tsaid. "Before I was a Scientologist I never agreed with psychiatry, and when I started studying the history of psychiatry, I understood more and more why I didn't believe in psychology."

Cruise, who was engaged to Holmes at the time, insisted that "there is no such thing as a chemical imbalance," and that through "vitamins and exercise," a person's problems can be cured. "Drugs are not the answer," Cruise told Lauer. "I think there's a better quality of life."

In a 2005 Facebook Q&A with Today fans, Lauer called that 2005 interview his most "awkward" ever. "It was one of those unforgettable moments that became a part of pop culture," he said.

(E! and NBC are both members of the NBCUniversal family.)