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The Antidepressant Dilemma (long read)
NY Times ^ | November 21, 2004 | JONATHAN MAHLER

Posted on 11/20/2004 7:07:55 PM PST by neverdem

Looking back, Mark and Cheryl Miller would have done a lot of things differently with their 13-year-old son, Matt. They probably would never have left Lenexa, Kan. They would have sent him to a different school, and they certainly would have chosen a different therapist. But most of all, they wouldn't have given him Zoloft. ''It's not a pleasant thing living with the thought that you had a hand in your son's death,'' Mark Miller told me recently. ''Making him take those pills was done out of love for Matt, but it was still the wrong thing to do.''

We were on our way back from Mark and Cheryl's Wednesday-night Bible-study class. I was riding with Mark, who had come straight from the advertising agency where he works as a vice president and creative director. A young-looking 55, with neatly combed hair and wire-rimmed glasses, he was wearing a striped Polo button-down and pressed blue jeans. A few minutes later Mark eased his white Volvo into the garage of their home, a meticulously decorated two-story Tudor in Overland Park, Kan. The Millers moved here from Lenexa, like Overland Park a suburb of Kansas City, in the summer of 1996, though they'd been talking about relocating for years. They liked Lenexa, but Mark was doing well, and they could afford a bigger house in a more upscale neighborhood.

Their new home was only 30 minutes away from their old one, but it meant a new school district for their two children. Their 15-year-old, Jenny, was going to be a freshman in high school and was nervous about the move. Her 12-year-old brother, Matt, a slight, fair-haired boy who wore skateboard-style clothing, was excited. As a Cub Scout, he had built the fastest pine-wood derby car in his age division, and he was looking forward to taking flying lessons at a flight school near their house when he turned 14.

School started, and Jenny was doing fine. She tried out for the drill team, and while she didn't make it, she did meet some new friends at the auditions. Things were a little harder for Matt at Harmony Middle School. First of all, it was big; the Overland Park area had become very popular in recent years, and Harmony had been forced to temporarily accommodate 700 students, nearly twice as many as it had been designed to. Starting in the seventh grade also put Matt at a disadvantage, as most of his classmates had already been together for a year. Though he was small for his age, Matt was popular with the girls. Still, he was clinging to his old friends more tightly than the Millers had hoped. On weekends, Mark and Cheryl often found themselves driving him to and from Lenexa.

For a while, the Millers thought Matt was just going through a normal period of adjustment; a few months in, though, they noticed a change. ''At the beginning of the school year, Matt was getting calls from girls all the time,'' Cheryl, a petite woman in a stylish gray jacket and black pants, told me. ''But around Christmas we saw things weren't connecting for him as well. The kids weren't letting him in. He started getting quiet, withdrawn.'' The Millers' theory is that the other boys were jealous. ''We think some of the guys were blocking him out because all of the girls were calling him,'' Mark said. ''He probably crossed somebody with someone's girlfriend.''

By midwinter the signs were more pronounced. His grades were falling. Always an A-B student -- he had excelled in math in particular -- he now had a D and an F. In February, Matt was caught forging his father's signature on several midterm progress reports. The Millers were called to the school for a conference. As the second semester continued, Matt's problems multiplied. One of his teachers reported that Matt was breaking pencils in class and failing to interact with his classmates. Several instances of ''unsatisfactory conduct'' were brought to the attention of the principal.

In April, the school put Matt in a special-needs class for an hour every afternoon. Neither his attitude nor his behavior improved, though he did start going steady with a girl in May. Around that time, a counselor at Harmony suggested to Mark and Cheryl that they seek therapy for Matt during the summer. The Millers, who knew by now that Matt was unhappy though they weren't sure why, thought this was a good idea. They were eager to help Matt while school was not in session; that way, he could start fresh in the fall. They initially wanted Matt to see a social worker recommended by the school, but their insurance did not cover that therapist. In the end, they chose a psychiatrist, telling themselves that this might be for the best in case medication was required. Matt didn't want to go. ''He said to me, 'Mom, I'm not crazy,''' Cheryl recalled. Mark added: ''I remember telling him, 'Matt, this is good.' We would all love to pay someone to help us work through our problems.''

On June 30, 1997, the Millers took Matt to see Dr. Douglas Geenens, a child psychiatrist referred to them by Matt's primary-care physician. In addition to the doctor and the Millers, both Mark and Cheryl remember there being two other people in the room, who Dr. Geenens explained were his trainees. Matt sat silently for almost the entire 50-minute session. Cheryl did most of the talking, sketching out Matt's emotional deterioration since the start of the calendar year.

Matt's next appointment with Dr. Geenens was scheduled for July 21, a Monday. Mark and Cheryl recalled the details for me: Matt took a 30-minute test for attention deficit disorder and spent 15 minutes filling out a Children's Depression Inventory form, a standard tool for measuring depression in kids. At the end of the session, Dr. Geenens suggested that Matt try Zoloft. He gave the Millers three sample bottles with seven 50-milligram tablets in each and told them to make sure that Matt took one a day. The Millers had never heard of it. ''The only thing I was aware of was Prozac,'' Cheryl told me. ''I asked him why are you prescribing Zoloft?'' Dr. Geenens answered that Zoloft was newer and more refined than Prozac. Cheryl asked if there were any possible side effects. Dr. Geenens said they should be on the lookout for stomachaches or insomnia. The doctor had no appointments available until the middle of August, but he wanted the Millers to call in a week and let him know how Matt was doing.

Two days later, Mark took the kids to visit his mother at her apartment in Sioux City, Iowa. Their plan was to spend a few days there, then bring Mark's mom back to Overland Park for the weekend -- they had tickets to a play in Kansas City -- before dropping her back home on their way to a family vacation on a lake in Wisconsin. Matt spent much of his time in Sioux City swimming in the pool at his grandmother's apartment complex. They came back on Friday and all went out to dinner. ''He was sitting across from me, and I remember asking him to quit stomping on my feet,'' Cheryl told me. ''I think back to that now -- he couldn't sit still.'' At lunch after church a couple of days later, Matt's grandmother also noticed that he seemed restless and agitated.

The Millers were leaving early Monday morning for Wisconsin. On Sunday night, July 27, at around 11:30, Matt was still on the phone with his girlfriend. Mark went to his son's room to tell him to hang up and go to bed. ''I didn't yell at him, but I was firm,'' Mark recalled. Matt threw the phone down and angrily slammed the door in his father's face, something he'd never done before. Mark went back to his room and asked Cheryl if he should go back in and talk to him. Cheryl thought they ought to wait until the morning. ''He's finally just getting settled,'' she told Mark. ''We don't want to rile him up again.'' When Cheryl went in to wake Matt up the following morning, she found him hanging by a belt from a laundry hook in his closet.

It didn't take long for Mark's thoughts to turn to the Zoloft: ''It was the only thing that had changed that week. What else could we attribute it to? He's on a new medication, and he takes his life.'' When he spoke with Dr. Geenens later that morning, Mark asked if there was something in the drug that might have triggered suicidal behavior. The doctor told him that he wasn't aware of anything.

At the time, there wasn't much reason for Dr. Geenens to have known otherwise. Over the course of the past two years, however, the debate over whether antidepressants, particularly those known as S.S.R.I.'s -- selective serotonin reuptake inhibitors -- can trigger suicidal behavior in teenagers has migrated from the margins of the medical community to the front pages of newspapers. Adding to the controversy was public outrage at revelations that a number of pharmaceutical companies had deliberately withheld damning information about S.S.R.I.'s -- specifically, data from clinical trials that suggested that these drugs were both more dangerous and less effective for adolescents than millions of consumers had been led to believe.

Beneath the rancor was a complicated question. Patients who were being prescribed antidepressants were, by definition, vulnerable to suicidal behavior; it was difficult to determine where the effects of depression ended and the effects of the drug began. What's more, psychiatrists had been aware for decades that the risk of suicide increases when patients first start emerging from depression. Rollback, as this is known, is thought to be caused by a depressed patient's energy level rising ahead of his or her mood. No longer lethargic but still deeply unhappy, for a brief period some patients who had been too apathetic before to harm themselves now had the wherewithal to do so. Were patients taking S.S.R.I.'s experiencing rollback? Or was there something specific about S.S.R.I.'s that triggered suicidal impulses?

Things came to a head this fall with the F.D.A.'s affirmation of a link between antidepressants and suicide ''ideation,'' or suicidal thoughts, in adolescents. Now all antidepressants, including S.S.R.I.'s like Prozac, Zoloft, Paxil, Lexapro, Luvox and Celexa, must carry a black-box warning label, the regulatory agency's strongest kind, making a possible suicide link explicit and all but ensuring a significant decrease in their use among young people. Far from providing closure on this complicated issue, though, the F.D.A. ruling may ultimately raise more questions than it answers.

Many child psychiatrists, who as a group have come to rely on S.S.R.I.'s to treat adolescent depression, seem to think the F.D.A. overreached. Studies have shown that one out of every 20 teenagers has suffered at least one bout of severe depression in his or her life, and adolescent depression can be especially difficult for doctors to manage. Teenagers are often resistant to psychotherapy, and unlike adults, who can quit a job or leave a marriage that might be aggravating their unhappiness, adolescents are almost always stuck with their lots. Doctors who treat young people -- child psychiatrists, pediatricians and general practitioners alike -- were wary of tricyclics, the previous generation of antidepressants, because of the risk of overdose. (The difference between an effective dose and a lethal one could be as small as six tablets.) But it is much harder to OD on S.S.R.I.'s. While the F.D.A. has approved only Prozac for depression in children and adolescents, doctors are free to prescribe any of these drugs ''off label'' for a patient group not specified on the packaging. And they have: between the early 90's and 2001, the prescription rate of antidepressants for those under 18 more than tripled. In 2002, 11 million antidepressant prescriptions were written for children and adolescents in the United States. Doctors recommended the drugs primarily to treat depression, but also for other emotional problems, from anxiety to shyness to obsessive-compulsive disorder.

The pharmaceutical companies are clearly making a product that most psychiatrists consider critical to treating depressed adolescents. Not prescribing these drugs may very well pose a greater threat than prescribing them. Studies have shown that areas in which antidepressant use among young people is widespread have experienced a dip in teenage suicide rates; according to Dr. John Mann, a suicide expert at Columbia University, fewer than 20 percent of the 4,000 adolescents who commit suicide in America each year are taking or have ever taken antidepressants. ''It would be ludicrous to think that antidepressants could actually contribute to suicide in the United States in any kind of significant way,'' Mann told me. ''The vast majority of teen suicides are actually committed in the absence of antidepressants.''

The F.D.A. was essentially forced to strike a balance between the cost of the few and the good of the many. Did the agency give too much weight to the few? ''For a family who has lost a child shortly after going on Prozac or some other S.S.R.I., I don't know what I can say to them,'' Dr. John Walkup, a child psychiatrist in Baltimore, told me. ''But it's dangerous to make public policy based on rare and tragic events.'' Still, as Mark and Cheryl Miller will tell you, it's no less dangerous to ignore them.

In the months after Matt's death, the Millers confronted a sort of grief that most parents cannot begin to imagine. Both of them took a month off from work. They started every day with an early-morning walk around a lake near their house. They talked about Matt and all of the things they might have done differently. Jenny made the drill team that fall, and the Millers attended every Friday-night football game to watch her perform at halftime. They found that they felt better when they were out of the house, so they took lots of weekend trips and visited family members on Thanksgiving and over Christmas. They also went out with friends and colleagues as much as possible. ''We both strived for normalcy again, which we knew would never be quite the same,'' Mark told me. Always religious people, the Millers immersed themselves even deeper in Christianity and met weekly with a Christian grief counselor.

But Mark was also hunting for answers. He soon found what he was looking for, or rather whom. During one Internet search, he happened across the Web site of Ann Blake Tracy, author of ''Prozac: Panacea or Pandora?'' a self-published 424-page screed against S.S.R.I.'s. Unless you are desperate, as most people typing words like ''suicide'' and ''antidepressants'' into Google most likely are, Tracy's Web site does not invite lingering. A picture of her in what looks like an out-of-focus 70's yearbook photo is surrounded by text that is the online equivalent of someone yelling outside the gate of the White House -- angry black-and-red type interrupted with WARNINGS about the dangers of going off these drugs cold turkey, and invitations to ''click here'' to read more personal horror stories.

Even among the most ardent opponents of S.S.R.I.'s, Tracy is an extremist. When I met her this fall, she told me that she began her campaign against antidepressants in 1989, when two friends in Salt Lake City, both Mormons, became alcoholics shortly after going on Prozac. Since then, she has come to believe that antidepressants have played a role in just about every high-profile act of violence the world has seen, from the death of the Princess of Wales (''When Princess Di was killed,'' she said, ''I called the police in Paris and said you've got a driver on Prozac'') to the 1999 shootings at Columbine High School to the terrorist attacks of Sept. 11. But as an early anti-S.S.R.I. activist, Tracy was a godsend to families like the Millers, who were relieved to discover someone who could vindicate their hunch about these drugs.

Mark pulled Tracy's number from her Web site and called her. After hearing Matt's story, she steered Mark to some other sources, and he continued his research. He soon learned that the possibility of a link between S.S.R.I.'s and suicide had first been raised many years earlier by two Harvard Medical School psychiatrists, Dr. Martin Teicher and Dr. Jonathan Cole, in a paper published in early 1990 in The American Journal of Psychiatry titled ''Emergence of Intense Suicidal Preoccupation During Fluoxetine Treatment.'' The doctors observed that six of their adult patients experienced ''intense, violent suicidal preoccupation'' within two to seven weeks of starting on fluoxetine, the generic name for Prozac, the first of the S.S.R.I.'s to reach the American market.

Teicher and Cole didn't want to overstate the significance of their findings -- five of the six patients had entertained thoughts of killing themselves at some point earlier in their lives -- but the onset of suicidal thinking had occurred so suddenly after the beginning of treatment that a prospective link was hard to ignore. ''The purpose of this report is to suggest the surprising possibility that fluoxetine may induce suicidal ideation in some patients,'' the doctors wrote, reporting that the phenomenon appeared in about 3.5 percent of their patients taking the drug.

About a year later, Dr. Robert A. King, a child and adolescent psychiatrist at the Child Study Center at Yale Medical School, noticed something similar in several of his patients between ages 10 and 17. Dr. King had prescribed Prozac for 42 of his young patients suffering from obsessive-compulsive disorder (but not depression), 6 of whom experienced what he later described in The Journal of the American Academy of Child and Adolescent Psychiatry as ''self-injurious ideation or behavior'' -- behavior that none of them ha