Since its debut in 1982, Accutane has been hailed as a miracle drug and assailed for its severe side effects.

A potent drug with power to clear up persistent acne, it also has been linked to instances of depression and suicide.

But homicide?

That's what the defense attorney for John J. Mullarkey Jr. is expected to argue this week.

Jury selection is scheduled to start tomorrow for Mr. Mullarkey, 20, of Monroeville, who is charged with fatally stabbing his 16-year-old ex-girlfriend Demi Cuccia in 2007. The Gateway High School cheerleader was stabbed 16 times in the chest, and Mr. Mullarkey sliced his own throat in an apparent suicide attempt.

The case is believed to be one of only two homicides cases in which Accutane has been cited as a factor -- and the first to go to trial.

Mr. Mullarkey's attorney, Robert E. Stewart, has never denied that Mr. Mullarkey stabbed Demi. In court filings and previous proceedings, he indicated he will pursue a "diminished capacity" defense and will argue that Mr. Mullarkey was mentally impaired due to his use of Accutane.

Mr. Stewart also has said it is a case of first impression, meaning he has found no precedent for his planned Accutane defense.

To win a diminished-capacity defense, an attorney must show that a defendant could not form specific intent to kill because of some kind of mental impairment. Attorneys may present that argument when they are seeking a third-degree, rather than a first-degree murder conviction -- which carries a mandatory life sentence

The defense typically is used when the defendant was drunk or otherwise intoxicated. Neither Mr. Stewart nor prosecutors could be reached last week, but prosecutors are expected to rebut the Accutane argument.

Accutane, the brand name for the drug isotretinoin, was connected to severe birth defects in the 1980s and nearly taken off the market by the FDA as a result. Women who use it now are required to take a pregnancy test before starting treatment and are instructed to stop taking the drug immediately if they become pregnant.

In addition, Roche Pharmaceuticals, the drug's manufacturer, has paid millions of dollars to patients who filed lawsuits after suffering inflammatory bowel disease while taking Accutane.

Some advocates and researchers have blamed suicides on Accutane use, among them U.S. Rep. Bart Stupak, whose 17-year-old son died in 2000. The Michigan Democrat brought nationwide attention to the issue and held two congressional hearings on Accutane and depression.

But the only other known case in which a homicide suspect contended Accutane was a factor in a slaying occurred in 2006, when Hans Peterson, then 28, stabbed Chicago dermatologist David Cornbleet to death. Dr. Cornbleet had prescribed Accutane to Mr. Peterson, who later told police he killed his doctor because of the drug's debilitating side effects, including impotency.

Mr. Peterson fled to the Caribbean island of St. Martin, which is shared by the French and Dutch, and confessed to authorities there. Mr. Peterson, whose mother is French, claimed French citizenship and was jailed on the Caribbean island of Guadeloupe, which also is under French control. France does not extradite defendants who could face the death penalty.

In media interviews and online postings, Mr. Peterson's relatives said they noticed a marked difference in his behavior after he started taking the drug.

"It made my son psychotic," Dr. Thomas Peterson, a sports medicine specialist from Eugene, Ore., told WLS-TV in Chicago.

Accutane's label warns that it may cause depression, psychosis or suicide. In response to questions about Mr. Mullarkey's case, Roche Pharmaceuticals in a statement said 14 million people have used it worldwide, and: "Numerous studies have failed to find any cause-and-effect relationship between Accutane and psychiatric events or behaviors.

"Reports of violence and/or aggressive behavior in patients who have taken isotretinoin are rare," the company said. "Case reviews and analyses of reports of violence or aggressive behavior in these patients have shown no objective evidence of a cause-and-effect relationship between isotretinoin and aggression and/or violence in any of the cases."

A 2006 study led by Dr. Anick Berard, of CHU Sainte-Justine Research Centre in Montreal, showed that patients who took Accutane were 2.68 times as likely to be hospitalized for depression. Dr. Berard said her study, which tracked patients in Quebec, took into account that Accutane patients, most often adolescents with skin problems, are more likely to have low self-esteem.

Despite the drug's dangers, she said, dermatologists will fight to keep it on the market because it is the most effective way to treat severe acne. Dr. Berard said dermatologists should prescribe Accutane only after other treatments have failed and should schedule monthly check-ups for patients to monitor their mental health.

"I hope that now those who come and see [dermatologists] with acne and with an unstable mental state, if they do prescribe Accutane to these people, I hope that they will monitor them," Dr. Berard said.

"But a lot of physicians are working in silos: 'I'm a dermatologist. I work with acne. Psychiatrists deal with depression.' "

Pharmacist Daniel Wagner, who is scheduled to testify as a defense witness in Mr. Mullarkey's case, said Mr. Mullarkey, then 18, quit using the drug three days before the killing on Aug. 15, 2007, which apparently occurred in the midst of the couple's breakup.

Dr. Wagner, owner of NutriFarmacy in Hampton, said he doesn't have specific experience with Accutane. But he said he will testify about the dangerous effects of a cold-turkey withdrawal from a powerful drug.

"In my opinion, the issue is the cessation of the drug had something to do with the action," Dr. Wagner said. "It is a double-edged sword -- staying on it too long or going off too quickly."