Steven Soderbergh, rightly considered one of Hollywood’s smartest movie makers, is at his cleverest in “Side Effects,” a canny, cunning big idea thriller in a minor key, an engrossing zeitgeist whodunit about Wall Street, Big Pharma, prescription drugs and the power we give psychiatry and psychologists.

Put simply, it’s about a death, perhaps caused by an under-tested depression drug.

Channing Tatum plays a Wall Street type just getting out of prison for securities fraud.

Rooney Mara (“The Girl with the Dragon Tattoo”) is Emily, his seemingly-overwhelmed wife, a morose beauty burdened by the responsibilities she now carries (she’s the one working) and the memory of the life they lost.

Her attempted suicide-by-car puts her in the care of Dr. Jonathan Baker (Jude Law), a seemingly sincere psycho-therapist who must come up with a drug — on the fly — that keeps a distraught but apparently sane Emily out of the hospital.

We’ll do this and then that drug, he suggests. And if one or the other produces problems, we’ll prescribe something else to counter those. How about this new thing, the one she’s seen the ads for on TV – “Ablixa”?

“Side Effects” nicely describes the slow-moving “fog” of depression as waves of it overwhelm Emily. And it plays like a case-study in her treatment by drugs – her downcast behavior replaced by other manifestations of “not quite right.” Suddenly, she has energy and can function at work and in her marriage, where “new energy” translates to a vigorous sex life. But she’s up at all hours, sleepwalking. She can’t remember things.

Then, a crime happens and we wonder if it was the drug, the doctor (legally paid by the pharmaceutical company to test the drug on patients), the patient’s predisposition (Catherine Zeta-Jones plays her previous doctor) or something else that led to tragedy.

It’s a film that sees quiet menace in the everyday. Soderbergh elegantly suggests that if you’re suicidal, every trip down to the subway, every boat ride in the harbor, every moment behind the wheel or meal prepared with sharp knives has the threat of an impulsive, irreversible act.

Soderbergh, working from a Scott Z. Burns (“Contagion”) screenplay, transforms this tricky mystery into hints of something trickier – Wall Street machinations, the murky relationship between psycho-therapists and the courts, between doctors and pharmaceutical companies.

“You watch the commercials on TV,” one puzzled character complains. “People get better.”

Law uses his years of playing cads as useful baggage here, giving suspicious layers to this married, overextended workaholic. Tatum is never more believable — no matter what the character — than when he’s in a Soderbergh movie. He should single-handedly prevent Soderbergh from going through with his announced retirement.

And Mara, trussed up to resemble a young, troubled Kristen Scott-Thomas, retains the touch of “unstable” she wore so well in the Hollywood version of “The Girl with the Dragon Tattoo.” Is she sleepy-eyed, or psychotic, deeply depressed or poker-faced?

“Side Effects” loses some momentum in its third act, piling on implausibilities as it grasps for a satisfying conclusion. But even then Soderbergh never lets things slip from the implausible to the impossible. Remember, even in the “Ocean’s Eleven” movies, he was too smart to let that happen. Is he smart enough to see he has no business retiring after this year?

 (Roger Moore’s interview with Rooney Mara is here.)

MPAA Rating: R, for sexuality, nudity, violence and language.

Cast: Jude Law, Rooney Mara, Channing Tatum, Catherine Zeta-Jones

Credits: Directed by Steven Soderbergh, written by Scott Z. Burns. An Open Road release.

Running time:1:45