Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial

by Alison Bass

  Author's Note vii

  Prologue: 2004 1

  1. Martin Teicher and the Wonder Drugs, 1988-89 7

  2. Rose Firestein v. New York City, 1989 15

  3. Donna Howard's Quest to Help Her Adopted Daughter, 1990 23

  4. The Empire Strikes Back, September 1991 29

  5. Rose Firestein's Big Gamble: Suing the Pharmaceutical Industry, June 2004 47

  6. The Brown Connection, 1995 57

  7. Donna Howard Talks to the Press and Becomes a Pariah, January 1996 73

  8. The Humiliation of Martin Teicher, October 1996 79

  9. Eliot Spitzer's Crusaders Win Round One against GlaxoSmithKline but Get Knocked Off Course in Round Two, July 2004 91

  10. A Tale of Two Psychiatrists Named Martin, Spring 1998 103

  11. Tonya Brooks Becomes a Nomad, and Rose Firestein Fights to Protect Florida's Foster Children, 2000-2001 117

  12. Donna Howard Discovers That in the Nonprofit World of Patient Advocacy, Money Shouts, Fall 2002 125

  13. Rose Firestein Begins Probing the Paxil Puzzle, Summer 2003 137

  14. Rose Firestein's Epiphany, Winter 2004 153

  15. How Rose Firestein Found the Smoking Gun Memo and Converted the Skeptics, Spring 2004 165

  16. The New York AG v. GlaxoSmithKline, June 2004 179

  17. Wherein Rose Firestein Goes to Court and Annoys a Federal Judge, July 2004 187

  18. GlaxoSmithKline Comes to the Table, August 2004 197

  19. Martin Teicher Is Vindicated, and Rose Firestein Takes a Bow, Fall 2004 207

  Epilogue: Rose Firestein Gets Run Over and Survives, and Donna Howard Turns Out to Have Been Right All Along 221

  Acknowledgments 237

  Notes 239

  Index 253

  IN NOVEMBER 1995, when I was a reporter for the Boston Globe, I received a message from the city desk. A woman had called with an anonymous tip, something to do with the misappropriation of funds from the Massachusetts Department of Mental Health, the state agency that oversees the care of people with mental illness. The phone message was forwarded to me because I was the Globe's mental health reporter. When I called the number on the message slip, a woman named Donna Howard answered the phone. She said she worked in the psychiatry department at Brown University and had found evidence of wrongdoing by researchers in her department. Clinical trials were not being conducted properly, and her boss, Dr. Martin Keller, chair of Brown's psychiatry department, was collecting funding from a state mental health agency under false pretenses. Would I be interested in meeting with her? I would.

  It was the beginning of a series of stories I wrote that opened my eyes to the way medical research was being conducted in this country. The first story, which ran in the Boston Globe in January 1996, reported that the financially strapped mental health agency in Massachusetts was paying the psychiatry department at Brown University School of Medicine hundreds of thousands of dollars for research that apparently wasn't being conducted. I followed that story up with several articles about other research and billing controversies in the psychiatry department at Brown.

  At the same time, I was also covering the astonishingly successful emergence of a class of new antidepressants called SSRIs (selective serotonin reuptake inhibitors). These psychoactive drugs-Prozac, Zoloft, Paxil-were fast becoming blockbusters, earning their manufacturers billions of dollars in sales. However, there was growing concern about their safety. In 1990, Dr. Martin Teicher, a psychiatrist at McLean Hospital and Harvard Medical School, together with two colleagues, published the first case report linking Prozac to suicidal thoughts and behaviors in some patients. Their case report came under heavy fire from the pharmaceutical industry and prominent members of the psychiatric community. I remember interviewing Teicher at the time and thinking that he was either very brave or unusually foolhardy to buck the wave of excitement sweeping his profession over these new antidepressants. The mishaps that befell Teicher in the years after he questioned Prozac's safety are part of my narrative.

  Then in 1999, I received another anonymous tip: Martin Keller, still Brown's chief of psychiatry, was earning hundreds of thousands of dollars in personal income from the very companies whose drugs he was touting in medical journals and at conferences. That tip led to a frontpage story in the Boston Globe on Keller's extensive financial ties to the pharmaceutical industry. Martin Keller declined to be interviewed for this book despite numerous requests left with his office and with the Brown University public relations office.

  The story continued to unfurl after I left the Globe. In 2003, the New York State attorney general's office began investigating the pharmaceutical industry. The investigation, led by a spunky newcomer to the AG's office named Rose Firestein, focused on drugmakers' widespread practice of disclosing only positive results about new drugs and withholding the negative research outcomes. What Firestein and her colleagues found raised serious questions about the veracity of Glaxo SmithKline's claims that Paxil was a safe and effective drug for children and adolescents. In this book, I recount the story of how Firestein found and assembled the clues that Martin Teicher, Donna Howard, and other whistle-blowers had left before her. My narrative tells the larger story of how pharmaceutical companies and their partners in the research community pulled the wool over the public's eyes with tacit assistance from the Food and Drug Administration, the premier agency in charge of protecting the nation's health.

  All of the people written about in this book exist. There are no imaginary scenes or characters. When I describe someone as feeling, thinking, or recalling something, the emotion, thought, or memory was explicitly described to me by the person to whom it is attributed. In the case of key scenes, I was nearly always able to contact others present to confirm that my subjects' memories were accurate. The names in this book are real, although I have used one person's middle name.

  The material for this book was culled from dozens of interviews with primary sources and key experts and from thousands of pages of university, corporate, and government documents. In addition, I reviewed transcripts of government meetings, disciplinary hearings, and legal proceedings and collected hundreds of relevant newspaper articles. Many of these documents are cited in the Notes.

  Alison Bass

  2008

  AT SIXTEEN, TONYA BROOKS was painfully shy, with long blond hair, round cheeks, and blue green eyes that changed color with the light. She earned decent grades at Pflugerville High School, twenty minutes outside Austin, Texas, but she was too uncomfortable around other kids her age to take part in extracurricular activities. Instead, she would come home after school every day and do her homework or watch television. She noticed a commercial on TV for a drug called Paxil. It showed a teenage boy, who, like her, felt self-conscious all the time, as if everyone were staring at him. After taking Paxil, the boy changed; he became confident and carefree, and wherever he went, friends flocked to him. Tonya wanted to be like that. But she didn't say anything to her parents about her longings or her fears.

  One day when she was almost sixteen and a half, Tonya drove to her favorite Subway to get a six-inch ham sub. As she pulled into the parking lot, she saw a group of kids she didn't know. I can't do this, she said to herself, and drove home. When her mother asked her where her sub was, Tonya started crying. "I can't go out anymore; I can't go anywhere," she said. "I don't know what's wrong with me."

  Her mother suggested they go and talk to the family doctor about Tonya's anxiety. Tonya asked the doctor about Paxil, and the do
ctor said it might help. So in January 2004, Tonya began taking Paxil. But instead of making her feel better, it made her restless, agitated, and unable to sleep. It also made her mean.

  Tonya used to care about her schoolwork and feel guilty when she didn't do well. Now she just didn't care. In fact, she didn't give a damn. And if her mother so much as asked how her day had gone, she would yell, "Don't talk to me. I hate you!"

  Tonya had always had a bump on her left elbow, but she had never given it much thought. A month or two after she started taking Paxil, she decided that the bump should be removed, so she asked her father how he would remove such a bump. He kidded that she could use an X-Acto knife. He thought Tonya was kidding too.

  She wasn't. She found her father's X-Acto knife and starting digging out the bump on her elbow. It started bleeding badly, and her dad put some Band-Aids on the wound. That evening, as Tonya was lying in bed unable to sleep, she realized that the cutting hadn't hurt. In a weird way, it had made her feel better.

  Around this time, Tonya went back to their family doctor, who prescribed Ambien as a sleep aid. It didn't help much: she'd lie awake at night and think about how awful she felt. One afternoon, at her parttime job at the OfficeMax in Round Rock, five miles away, another employee there accused Tonya of stealing some money, which made her feel bad. On her break that day, she noticed that someone had left a box cutter lying around in the back of the store. She took it into the bathroom and cut into the underside of her wrist-not enough to open a vein, just enough to bleed. It didn't hurt, and again, it seemed to make her feel better.

  After that, she always cut herself in the same place, to keep the wound fresh. She covered the cuts with her watch and told no one. She didn't confide in anyone, mostly because she was afraid they would take her medicine away. She kept hoping the Paxil would start working, that it would make her feel better about herself.

  One evening, Tonya was counting the money in her till with another employee, a kindly gentleman in his sixties. "What happened to your wrist?" he asked. Tonya lied and said she had been working in the garage with her father and had been cut by a tool. "That's a weird place to get cut," the man said. "Are you sure you didn't do that on purpose?" She told him no, she was fine.

  As Tonya's cutting became more and more frequent, she felt so depressed, especially at night, that she started thinking seriously about killing herself. She began planning her own funeral, picking out tapes she wanted played. To her relatives, she would say strange things like, "I want you to be happy when I die."

  Cheryl Brooks, Tonya's mother, saw the radical change in her daughter but didn't understand what was happening. "She got mean, very sharp," Cheryl told me years later. But she had no idea Tonya was mutilating herself or that she felt suicidal. "I've got two older children and I didn't see it," Cheryl said, her voice pungent with regret. "I just didn't put two and two together."

  On the evening of May 30, 2004, Tonya swallowed all the pills in her Paxil and Ambien bottles. That night, she crawled into bed with her parents, thinking that she wanted to be near them when she died. Several times that night her mother had to take Tonya to the bathroom because she had the dry heaves. "I thought it was the flu," Cheryl said. "She was really, really sick."

  But she didn't die. On her way to work the next day, Tonya had a car accident. "She hit the curb on both sides of the road and blew out her tires," her mother recalled. "We had to pick her up and bring her home"

  That evening, Tonya's mother discovered the empty Paxil and Ambien bottles and confronted her daughter. Tonya lied and said she must have accidentally taken all the Paxil after she had taken the Ambien, when she was half-asleep. Her mother let it go.

  Three days later, Tonya took her daily dose of Paxil and Ambien and went to bed. It was June 2, the very day that Eliot Spitzer, the attorney general in far-off New York State, filed an unprecedented lawsuit against GlaxoSmithKline, the maker of Paxil, accusing the British-based pharmaceutical giant of consumer fraud. The action was a gamble, some might say an act of sheer chutzpah. No lawmaker had ever before accused the drug industry of fraud for deceiving doctors and patients about a new drug. The lawsuit was the brainchild of a newcomer to Spitzer's office, a feisty litigator named Rose Firestein, who knew a thing or two about loneliness and despair. Firestein had made a career out of defending the rights of vulnerable children, traveling all over the country to provide legal counsel on their behalf. In the past few years, though, she had lost much of her eyesight, making travel difficult. Instead of quitting and going on long-term disability, as her doctors counseled, she found a spot on Eliot Spitzer's team in lower Manhattan. There, she began investigating the way powerful psychoactive drugs such as Paxil were being tested and marketed for uses not approved by the FDA.

  By 2003, millions of Americans were taking Paxil and other antidepressants in the same class (such as Prozac, Zoloft, and Celexa), and these bestselling drugs were earning the pharmaceutical industry billions of dollars in profits. For many people, the drugs worked. They lifted the fog of despair from adults who had been crippled with depression for years; they eased the anxieties of others hobbled by self-doubt; they may have even kept some people from killing themselves. But the drugs also seemed to exert a paradoxical effect in some patients, particularly children, making them more agitated and suicidal, not less. At the New York State AG's office, Firestein and her colleagues were not interested in making a medical judgment about the value of these drugs. The question they posed was this: in its rush to create a bestselling drug, had GlaxoSmithKline deliberately suppressed important information about the safety and effectiveness of Paxil in children?

  Thousands of miles away in Pflugerville, Texas, Tonya Brooks had no idea who Eliot Spitzer or Rose Firestein were or what they were up to. All she knew was that she was feeling sad and agitated and she couldn't sleep and she wanted to cut herself again. In the small hours of the night, Tonya propped up her left leg and started digging into it with a needle and her mother's cuticle scissors. Then she grabbed a paring knife from the kitchen.

  She sawed off some skin with the knife and discovered that it didn't hurt. Then she realized she didn't want to get her bed dirty, so she went into the bathroom. The wound got bigger and bloodier. It felt as if somebody else were doing the cutting.

  Suddenly, something in Tonya snapped. Sometime around two in the morning, she stumbled to her parents' bedroom and banged on the door. When Cheryl answered groggily, Tonya yelled, "I want my dad. Please tell Dad to come here"

  A few minutes later, her parents found her in the bathroom, blood all over the floor and a huge, gaping hole in her leg. Her mother screamed and fell to the floor. Her father grabbed gauze and tape to try to stanch the bleeding. He half-carried Tonya to the car, and they sped to the hospital, Cheryl driving like a maniac. Tonya lay bleeding in the backseat, her head cradled in her father's lap.

  he rhododendrons were in full, blush pink bloom as Martin Teicher hurried up the path to his lab at McLean Hospital in Belmont, Massachusetts. The psychiatrist paid no attention to the flowering bush or the magnificent maple tree that shaded the courtyard outside of the Mailman Research Center, making it such a hospitable spot for staff and patients to linger. All Teicher could think about was the startling admission that his patient had made in their weekly therapy session that afternoon. Ms. D., as he had taken to calling her, suffered from a depression so disabling that she could no longer work, although she had once been a successful business executive. When the thirty-nine-year-old woman first came under his care, Teicher had tried her on a potent antidepressant known as an MAO inhibitor. While the drug lifted her mood, it caused an extremely uncomfortable rash. So Teicher prescribed another antidepressant known as a tricyclic (for its three-ringed molecular structure), but this drug did nothing to dispel the woman's lethargy and sense of gloom. Electroshock therapy worked for a few months. Teicher then tried his patient on yet another tricyclic known as amitriptyline. Although the drug helped, it gave Ms. D. a rave
nous appetite. Her weight ballooned and she stopped taking the medicine. Ever since, she had lapsed into a deep despondency, sleeping all the time and withdrawing from family and friends.

  In the spring of 1988, Teicher decided to put Ms. D. on a new antidepressant about which he'd heard great things. Launched in the United States just a few months earlier, Prozac was a selective serotonin reuptake inhibitor (SSRI), so named because it blocked the uptake of a neurochemical called serotonin. Brain cells communicate by releasing "transmitter" substances into the space, or synapse, between them, and serotonin is one of the brain's key transmitters. Research indicated that in people with depression, the levels of a metabolite of serotonin appeared to be low. Some researchers theorized that if the surrounding brain cells were blocked from absorbing serotonin, the chemical would build up around the nerve endings of the brain and help alleviate depression. That hypothesis would later be discarded as too simplistic, but not before it became a compelling rationale for how Prozac worked.

  Yet the buzz about Prozac went beyond theory. A number of Teicher's colleagues had experimented with the drug before the Food and Drug Administration approved it for official use in January 1988, and several had experienced such good results that they'd taken to calling Prozac a wonder drug. It was easy to see why: The SSRI was the first new antidepressant to come along in a decade, and unlike older antidepressants, it could be prescribed in convenient one-a-day twenty-milligram capsules. Most important, it seemed to have none of the nasty side effects of the older drugs. Perhaps, some psychiatric researchers speculated, that was because Prozac influenced only one neurotransmitter in the brain; older antidepressants (such as the tricyclics) acted on several key neurotransmitters.

  In time, this theory would also prove to be flawed. The brain's circuitry is amazingly complex and interconnected, and dramatic changes in serotonin levels can trigger ripple effects in other important neurotransmitters, such as norepinephrine and dopamine. As many people would soon discover, Prozac and other SSRIs could cause far more dangerous side effects than their manufacturers initially let on.