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Steven Soderbergh said goodbye to directing, and the Berlinale which has hosted him more often than any other film festival, with the taut thriller "Side Effects" that drew cheers Tuesday.
The Hitchcock-inspired picture about intrigue and corruption in the pharmaceuticals industry is one of 19 movies vying for the festival's Golden Bear top prize.
Starring Jude Law, Catherine Zeta-Jones and Rooney Mara, the film is also what Soderbergh said is his last before he turns his back on Hollywood and devotes his time to painting and other pursuits.
"I just liked the idea of making a thriller as I near the twilight of my career," the 50-year-old director, who won an Oscar for his 2000 narcotics drama "Traffic", told reporters.
"Honestly, however long this break ends up being, I wanted this thing to be fun to make and to watch."
Rooney jumped in: "Did you just call it a break and not your retirement?" Soderbergh replied with a smirk: "Whatever."
Mara plays Emily, the wife of a Wall Street executive convicted of insider trading (Channing Tatum) who has just been released from prison.
She has a history of psychiatric treatment and finds it difficult to adjust to the new situation at home.
Enter Law as her new therapist who puts her on an experimental drug that a major company pays him to field test and that Emily's former psychiatrist (Zeta-Jones) also recommends.
When Emily's husband winds up stabbed with her fingerprints all over the kitchen knife, she says she cannot remember a thing about his killing and blames her medication.
The case of the shattered glamour couple captures the attention of the New York media and the suspicion shifts to the therapist who gave Emily the prescription.
Further plot twists come hot on their heels in what Soderbergh called an attempt to play with the expectations of the thriller genre.
"I've always tried to approach each film as if it destroys all the films that come before it," he said.
"I wanted to make something very, very lean, I wanted it to be all muscle. I didn't want an extra shot, an extra moment."
Law's character, a British doctor chasing success in New York, said he prepared for the part by talking to psychiatrists and patients about the widespread use of anti-depressants in US society and their omnipresent ads.
"I think it can be quite alarming," he said. "It's obvious that we have a tendency nowadays to look for the shortcuts. The advertising, which as we all know can have a certain sort of bias, has an effect on our relationship with pharmaceuticals which isn't necessarily a good thing."
Soderbergh captured Cannes' Palme d'Or top prize with his 1989 debut feature "Sex, Lies and Videotape" and went on to make a wildly diverse set of hits such as "Erin Brockovich", "Contagion" and the "Ocean's" movies with George Clooney and Matt Damon.
He has a long history with the Berlinale, presenting five of his films at the festival, more than at any other festival.
A jury led by Chinese director Wong Kar Wai will hand out its Golden and Silver Bear prizes on Saturday.