Accutane, the acne medicine that was prescribed to a Florida youth who crashed a plane into a skyscraper on Saturday, has long been controversial, with critics and proponents debating whether the drug can cause depression and suicidal behavior.

While no definite link has been demonstrated, the Food and Drug Administration was concerned enough about the possibility to require the drug carry a warning:

"Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide," states the medicine's warning label, which was agreed to jointly by the agency and the manufacturer, Hoffmann-La Roche.

Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said one small study had showed that "when people took Accutane [they] became depressed and when they had the Accutane taken away, the depression went away."

"That's the evidence that there could be a causal link," he said.

Because the study was so small, a prospective trial is being designed with the company to study the matter. It is just as likely to find a link as not, he said.

Attention has focused again on Accutane after investigators found that a prescription for the drug had been written for Charles Bishop, 15, who crashed a small airplane into a Tampa building last week. Police said a note found in the wreckage professed solidarity with Osama bin Laden. After teachers described him as a bright and patriotic youth, his behavior seemed all the more incomprehensible.

Yesterday, the St. Petersburg Times reported that Bishop's parents had entered a suicide pact in 1984 while they were teenagers. After a problem with paperwork prevented them from getting married, the two tried to poison themselves with car exhaust fumes.

When that failed, they reportedly decided to slash each other with a butcher knife, which resulted in Bishop's father being hospitalized with stab wounds. The couple later had Bishop, got married and divorced.

Accutane has been on the market since 1982 and has been used by hundreds of thousands of people. A half-million prescriptions were written in the United States last year, the manufacturer said.

It is reserved for intractable cases of acne and is sold under an increased security prescription system, mostly because pregnant women taking the medicine are liable to have babies with birth defects. The medicine is not given to pregnant women, and doctors strongly urge women not to become pregnant while taking the medicine.

While the FDA has about 140 reports of suicide after people took Accutane, the rate of suicide remains extremely low,, making it difficult to pin down which cases might have occurred anyway and whether cases were caused by the medicine.

Carolyn Glynn, vice president for public affairs at Hoffmann-La Roche, said the rate of suicide in the group of 15- to 24-year-olds taking Accutane was lower than the rate of the general population.

"Acne is closely related to depression -- there are strong psychological scars that go with the condition," she said, explaining why Accutane could reduce depression.

Douglas Jacobs, a Harvard Medical School psychiatrist who conducted a review of the drug for Hoffman-La Roche, said "the overwhelming evidence is there is no causal link."

"My worry is it is going to be legislated out of existence, and then you will have many more suicidal kids because they can't get their acne cleared up," said Lawrence Green, a Rockville dermatologist.

Experts agreed that no conclusions could be drawn in Bishop's case without knowing whether he was taking the drug, whether he had a history of psychiatric illness and whether his behavior changed after he took the medicine.

James O'Donnell, a pharmacologist at Rush Medical College in Chicago, has testified against Hoffman-La Roche in court cases. He said that while he did not want the medicine banned, "we need to make sure there is no over-promotion by the company suggesting either in advertising or by their sales force that this is not a significant side effect."