A popular honors student who played on his varsity high school basketball and baseball teams in rural Washington state, Corey Baadsgaard nevertheless would come home complaining that no one liked him.
His family physician prescribed Paxil, a popular antidepressant. But Baadsgaard, then 16, sunk deeper into depression. The doctor switched him to a different antidepressant, Effexor, and stepped up the dose over a three-week period from 40 milligrams to 300. The first morning Baadsgaard took 300 milligrams, he felt rotten and went back to bed.
Three years later, he said, he still has no memory of what happened next: no memory of taking a high-powered rifle into his third-period English class, of herding his classmates and teacher into a corner, of holding them at gunpoint for 45 minutes, of being persuaded by the principal into giving up his gun.
He spent 14 months in a juvenile detention center.
Baadsgaard and his father believe the antidepressants made him suicidal at first, then violent. The Food and Drug Administration -- based on such anecdotal evidence and the results of clinical trials -- is reconsidering its decision not to require that doctors and parents be warned about possible side effects of the drugs known as serotonin reuptake inhibitors.
The link to suicide was the focus of an FDA advisory committee meeting last month. But testimony from Baadsgaard and others who had turned violent while taking the drugs suggested to several members of the committee that the FDA should look more broadly at the medications' adverse effects.
Dr. Joseph Glenmullen, a Harvard Medical School psychiatrist who has studied serotonin reuptake inhibitors, said Baadsgaard's story was plausible. And he wondered whether antidepressants could help explain the rash of school shootings and murder-suicides over the last decade.
People who take antidepressants, Glenmullen said, can "become very distraught.... They feel like jumping out of their skin. The irritability and impulsivity can make people suicidal or homicidal."
Added Dr. David Healy, director of the North Wales Department of Psychological Medicine: "What is very, very clear is that people do become hostile on the drugs."
Glenmullen and Healy emphasized that parents, patients and doctors should be warned to watch for potentially dangerous reactions. However, both said they planned to continue prescribing the drugs to their patients.
The pharmaceutical companies and many doctors dispute the suggestion that antidepressants play a role in violent or suicidal acts.
Dr. Alastair Benbow, the European medical director for GlaxoSmithKline, Paxil's manufacturer, refused to comment on specific cases. But he said he didn't believe there was "any clear evidence that Paxil is linked with suicide, violence or aggression -- and certainly not homicide."
The source of aggressive behavior, doctors and mental health groups said, may lie with the illness and not the treatment. And failing to treat depression, they explained, could have consequences as grave as treating it.
"Suicide and violence are well-recognized outcomes of depression itself," Benbow said.
Although only one antidepressant, Prozac, is explicitly approved by the FDA for children, doctors routinely prescribe others to their young patients. The National Mental Health Assn. estimates that depression affects 1 in 33 children and 1 in 8 adolescents; Healy believes young people account for 1 million of the 20 million Americans who take antidepressants annually.
Most of the drugs carry no specific warnings about increasing the risk of suicide or violence.
But one company, Madison, N.J.-based Wyeth, warned doctors in a letter last summer that children taking Effexor in clinical trials had shown increased hostility and suicidal tendencies compared with children taking placebos. The company directed doctors not to prescribe Effexor to children.
And GlaxoSmithKline, during clinical tests on children with obsessive-compulsive disorder or depression, found that the percentage of children taking Paxil who became hostile -- which was defined as everything from angry thoughts to violent acts -- ranged from 6.3% to 9.2%. For those taking the placebo, the range was zero to 1%, according to published records.
Benbow said the trials provided evidence of increased hostility in children, particularly among those younger than 12 and with obsessive-compulsive disorder.
But Dr. Timothy Wilens, a pediatric pharmacologist at Massachusetts General Hospital in Boston, said that when he and his colleagues treated 82 children with antidepressants for a variety of psychiatric problems, "there were no serious outcomes" like suicide or homicide. Although a quarter of the patients had adverse responses like agitation, aggression, increased depression or irritability, Wilens said he didn't "know of any evidence that these medicines turn people into predators."
The link between antidepressant reuptake inhibitors and violence came under scrutiny 10 years ago in a trial stemming from the case of Joseph Westbecker, who weeks after starting Prozac killed himself and eight others at a Louisville, Ky., printing plant.
Twenty-seven survivors and relatives of the dead sued Eli Lilly, Prozac's manufacturer. The jury ruled in the company's favor after the plaintiffs' lawyers rested their case without presenting key evidence.
The judge suspected a behind-the-scenes deal between the drug company and the plaintiffs. An investigation showed that Lilly had given huge settlements to all the attack survivors and their lawyers.
In 1997, the judge changed the official record from a jury verdict in Lilly's favor to dismissal of a settled case. But the drug company had won the case in the eyes of public opinion.
"It's an example par excellence of the behind-the-scenes maneuvering that the companies have done repeatedly to obscure the side effects from public view," Glenmullen said.
Drug companies have not always won.
A federal jury in Wyoming in 2001 found against SmithKlineBeecham (now GlaxoSmithKline) in the case of Donald Schell, 60, who had been taking Paxil for two days when he killed his wife, daughter, granddaughter and himself. The jury found that Paxil could cause some people to become homicidal or suicidal, and that the drug was a "substantial" factor in the Schell murder-suicide. The company was ordered to pay relatives of the victims $6.4 million.
But most of the hundreds of cases against the makers of antidepressants have been dropped, dismissed or settled out of court. Only three have made it to trial, said Andy Vickery, a lawyer in the Schell case.
Vickery now represents defendants who have committed horrible acts while taking antidepressants. He recently decided to take on the case of Christopher Pittman, a youth who in 2001 killed his paternal grandparents and set their South Carolina house on fire. His trial is to begin in April.
At the FDA hearing, Pittman's father read a letter written by his son while he was in detention, about how while taking Zoloft he "took the lives of two people that [he] loved more than anything."
While on the drug, Pittman wrote, he "hated the whole world for no apparent reason." He got into fights and blew up at the smallest things. Things kept getting worse, he wrote.
"When I was lying in my bed that night, I couldn't sleep because my voice in my head kept echoing through my mind -- telling me to kill them -- until I got up, got the gun, and I went upstairs and I pulled the trigger," wrote Pittman, who is now 14.
In Baadsgaard's case, the violent outburst was completely out of character, said his father, Jay Baadsgaard. Corey never got into fights, his father said. In their family, he was the "hugger."
So, "as soon as it happened, we knew the drugs had to have something to do with it," Jay Baadsgaard said. Corey stopped taking the drugs while in juvenile detention and has not had any behavioral problems since, his father said.
Jay Baadsgaard remains angry at the drug companies, and said the drugs should be banned for children. "These drugs are hell," he told the FDA panel in February.
Corey Baadsgaard didn't go that far. He said he believed depressed kids should try counseling, and the drugs should be prescribed only as "the last resort."