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

by Alison Bass

  Marty believed he inherited his passionate nature from his Italian mother, who was a gifted artist and cook. But his drive, his need to excel in whatever task he applied himself to-that, he knew, came from his father. A stern, well-read man, Marty's father had always been interested in the sciences, but his own dad had died when he was in high school, so Marty's father had been forced to drop out of school and go to work to support the large family. The senior Teicher had become the manager of a millinery supply company in New York City and had scandalized his family by marrying a non-Jewish divorcee with a young child. He moved to Long Island and commuted back and forth to Manhattan, working long hours. Even as a child, Marty sensed that his father was not a happy man. Once his own children were born, Marty's father had insisted that his wife send her daughter from her first marriage to California to live with her father. It was a decision that would prove cataclysmic to Marty's half sister, who eventually died of a drug overdose, and one for which he, as a grown man, would look back and judge his father harshly. And yet the senior Teicher loved and indulged his oldest son.

  Like many kids, Marty loved building rockets and blowing things up in his chemistry lab. But he also had a sensitive, musical side. Blessed with a good ear, he learned to play the guitar at a young age. As a teenager, he would write his own songs and sing them to himself, strumming softly, late at night in his room. In college he toyed with the idea of becoming a "rock 'n' roller," but in the end he chose the vocation his father had envisioned for him: As a young child, Marty had suffered an unusual allergic disorder that prompted capillaries to burst and caused massive internal bleeding. He survived, and the illness left him and his family in awe of medical doctors and the miracles they could accomplish. By 1981, he had earned not only a PhD in developmental psychology from Johns Hopkins but an MD from Yale Medical School. He married Bev, his college sweetheart, when they were both in graduate school. She was a biochemistry doctoral candidate, also at Johns Hopkins, as bright and competitive as Marty, and determined to have both a family and a career. When Teicher embarked on his psychiatric residency at McLean, he was the father of a baby boy. But by the time his second child arrived, Teicher's full-speed-ahead style had hit a speed bump. His marriage was suffering. His wife felt that he cared more about his patients and his career than he did about his family. Teicher traced the strain between them back to the time his wife had a minor car accident while he was on call at the hospital. Their son was in the backseat, and even though neither she nor the baby was injured in the collision, Bev had been seriously rattled. She had called Marty at the hospital and asked him to come home. He did manage to find someone to cover for him, but he had felt he should go back to the hospital after a few hours. Bev had never forgiven him.

  WHEN CINDY MCGREENERY buzzed Marty that day with the news that a fellow psychiatrist wanted to talk to him about Prozac, he asked, "Are you sure this one is for real?" Cindy said yes. Dr. Allen Sandler was a psychiatrist practicing in Washington, D.C.

  "Okay, put him through."

  Sandler sounded distressed as he told Teicher about his patient, a prominent forty-nine-year-old attorney in Washington, D.C., who was depressed but had never been suicidal. Five or six days after starting Prozac, the man jumped off a bridge and killed himself. Sandler said he had just read Teicher's article in the American Journal of Psychiatry and had made the connection between his patient's death and the drug he had prescribed for him. He said he felt deeply guilty and wished that he had known about this side effect before prescribing Prozac.

  The man's estate, Sandler went on, was now tied up in probate because he had not executed a will. As a result, his wife was having a terrible time making ends meet. She was thinking of suing Lilly, he said. Would it be possible for Teicher to talk to her and the attorney she had retained-as a professional favor?

  Teicher groaned inwardly. Until now, he had resisted getting involved in any legal action against Lilly. But this case did sound horrendous. And since the publication of their Prozac paper, he and his colleagues had come across more patients who had become agitated and preoccupied with suicide after taking the drug. Several patients had turned uncharacteristically aggressive while on Prozac; some began mutilating themselves. In a follow-up article that Teicher and his colleagues would publish in 1993, they cited the case of one woman, with no prior history of depression, who began cutting herself after taking a high dose of Prozac. Her self-mutilation was so "incessant" that it eventually required plastic surgery, the McLean authors wrote. After this patient was taken off Prozac, her self-destructive behavior and suicidal thoughts disappeared.

  For its part, Lilly dismissed the McLean researchers' findings as completely unfounded. In the month before the 1990 case report was published, the drug company had flown two of its top scientists to Boston to show Teicher and Cole computer printouts of clinical trial data on three thousand patients. The results, they insisted, showed no correlation between Prozac and an increased risk of suicidal thoughts or behavior. But based on what he was hearing from colleagues and patients themselves, Teicher was beginning to believe the link between Prozac and suicidality was not as rare as he had originally thought. He was also starting to question Lilly's sincerity in ferreting out the truth about its popular new drug. He and colleagues had asked the drug company for a grant to do a more thorough prospective study that would compare patients on Prozac with those taking a placebo pill. Teicher was eager to do the kind of rigorous research that could put to rest criticisms that his original case report was anecdotal and thus not scientifically sound. But Lilly declined to fund the study. So, as it turned out, did the American Association of Suicidology, a nonprofit group that underwrote research to understand and prevent suicide, and the National Alliance for Research on Schizophrenia and Affective Disorder, a private organization that also funded research. Both groups received substantial money from the pharmaceutical industry, but that was probably not the only reason they were reluctant to fund a controlled trial that would examine Prozac's safety in a larger population. Such a study would be extremely expensive and time-consuming, and many psychiatrists just didn't see the need. They believed in Prozac: they had seen with their own eyes the way it worked to lift the mood of some of their most severely depressed patients, people who had not been helped by the older antidepressants. Teicher himself still believed that Prozac had a place in his medicinal tool kit. His coauthor Jonathan Cole liked to tease the younger man by saying that he was going to hire a balloon to fly over Boston with a trailer that read MARTY TEICHER STILL PRESCRIBES PROZAC.

  "Okay," Teicher told Allen Sandler on the other end of the phone. "I'll talk to them"

  THE MORNING OF the FDA meeting in Rockville, Maryland, Teicher walked from his hotel to the conference hall with the eminent British researcher Stuart Montgomery. It was a warm, sunny day, and the two men strolled past well-groomed green lawns and a large library with an impressive marble facade. When they arrived at the Parklawn Building, the squat concrete facility that served as the FDA's headquarters, security was unusually tight. With all the publicity over the Scientologists' aggressive campaign and the media backlash against them, FDA officials feared that things might get out of hand. All the attendees were required to walk through a metal detector and present their IDs. While there were only a handful of demonstrators outside with signs that read PROZAC KILLS, it was clear the FDA was leaving nothing to chance.

  The hall where the meeting would take place was huge. In the front of the room, Teicher and the other consultants sat at one wood-grained vinyl table, along with most members of the Psychopharmacological Drugs Advisory Committee. At another table presided a number of top FDA officials and the chair of the advisory panel, Dr. Daniel Casey, a psychiatrist with the Veterans Administration Medical Center and Oregon Health and Science University in Portland, Oregon.

  Casey was wearing a bulletproof vest.

  Fanning out from the tables on both sides were more chairs in a bleacherlike arrangement. To Teicher
's left huddled the lawyers and representatives from Lilly and other pharmaceutical companies, dressed almost identically in dark suits and crisp white shirts. To his right were more FDA officials and government scientists. Facing the conference tables were long rows of chairs for the public; tall microphones had been set up at the front of each aisle.

  Dozens of people had flown in to testify from as far away as Arizona, California, Florida, and even France. Teicher found himself moved, as speaker after speaker told devastating tales of loved ones who had killed themselves. Lee Ann Westover, the wife of the pop singer Del Shannon, recounted how her husband suddenly became agitated and sleepless after being prescribed Prozac for stress. "I want you to know suicide was totally out of character for my husband," she told the committee. Yet Del Shannon killed himself on February 8, 1990. Another woman, Sally Barrett, told how her seventeen-year-old daughter had shot herself to death after taking Prozac. A man by the name of Tucker Moneymaker, of Halifax, Virginia, said his wife, a churchgoing Cub Scout leader, had killed both of their sons after she was prescribed Prozac for "nerves." She shot herself as well and "is now in jail for murder," Moneymaker said.

  The testimony Teicher would remember most vividly involved a case he already knew something about. He had been interviewed by the FBI because the suspect in this murder-suicide had been taking Prozac and the FBI wanted to know if he thought the drug could have been a factor. The suspect's mother, a woman in her fifties, certainly thought so. In a halting French accent amplified by the microphone, Mrs. Richardson recounted how her son, a promising musician in his early twenties who managed a family-owned hotel on the French Riviera, had come home to the United States at Christmas complaining of headaches and low energy. His physician prescribed Prozac. A month after he returned to France, Mrs. Richardson said, she heard from a musician friend of his that her son wouldn't open his door to the cleaning lady. The cleaner had heard the young man singing opera at the top of his lungs and talking nonsense. "I sent him a telegram to call home immediately. The next day I called back and demanded they break into his apartment."

  Mrs. Richardson had gone over her allotted four minutes, and Casey interrupted her, telling her to wrap up in the next few seconds. She began sobbing. Her son, she said, had been found dead in his apartment with a young woman friend of his. She had been stabbed to death, and he had apparently killed himself with the same knife. "His hand was completely severed on the bed. There was a knife wound on his neck, cuts all over his body; the last blow was through his eye socket that pierced his brain. He died on the floor with the kitchen knife beside him."

  Mrs. Richardson had more to say, but her microphone was abruptly cut off. Ten or eleven more speakers came forward after her, and then finally Casey called a brief recess. It was time for the "scientific" part of the meeting. Dr. Paul Leber, director of the FDA's Division of Neuropharmacological Drug Products, led off. He stressed that the evidence to date from clinical trials-the only assessments "deemed reliable in the scientific community"-did not indicate an increased risk of suicidal thoughts, acts, or other violent behaviors from Prozac. The emphasis, Teicher thought wryly, was on the word "reliable," Leber having dismissed all of the anecdotal testimony with one sweep of his tongue.

  Teicher suspected that Leber had already made up his mind that the link between Prozac and suicidal behavior was a chimera, a delusion on the part of all the preceding speakers, who must have confused a natural worsening of depression with the effects of a new drug. Leber's words were judicious, but the FDA official made it clear that he didn't support stronger warnings on the drug's label about its possible suicide risks. "It is very difficult to tell, from where we sit, what more needs to be done at the present time," Leber said.

  Leber's attitude infuriated Teicher. He didn't understand why the FDA official, a respected psychiatrist from New York University, was being so closed-minded. It would take the distance of time for Teicher to understand what had happened that day. By then, a flood of lawsuits against Eli Lilly would force the disclosure of internal company memos from 1990. The Lilly corporate memos called Leber "our defender" and noted that "Lilly and FDA are working together on the suicide issue." Teicher didn't want to believe that Leber was in bed with the pharmaceutical industry; in all likelihood, Leber simply shared the concern of many psychiatrists that depressed patients might be scared off lifesaving drugs by publicity about their link to suicide. That afternoon, Leber concluded his remarks by saying that if a stronger warning was put on Prozac's label, "the result might cause overall injury to public health."

  Two other FDA officials voiced similar concerns. And then came the piece de resistance: a massive, two-hour-long presentation by scientists speaking on behalf of Eli Lilly. Dr. Jan Fawcett, an expert on suicide from Rush-Presbyterian-St. Luke's Medical Center in Chicago, talked about the incidence of suicide and the woeful undertreatment of depression in the United States. Dr. Charles Nemeroff, a psychiatrist from Emory University School of Medicine, gave what Teicher would remember as an elegant presentation, complete with detailed slides, on the research to date on Prozac and other SSRIs. Nemeroff dismissed Teicher's case study and a more recent finding of unexpected suicidal behavior among six adolescents on Prozac as being tainted by complicating factors.

  Nemeroff concluded that "there is simply no scientific evidence whatsoever ... that has established a cause-and-effect relationship between antidepressant therapy of any class and suicidal acts or ideation."

  Nemeroff's words were echoed by Gary Tollefson, a Lilly scientist who summarized what he said were the results of the drug company's controlled clinical trials of Prozac in the United States and abroad. Using an impressive array of slides, Tollefson showed data culled from trials with fifty-six hundred adult patients who had been randomized into three groups: Prozac, placebo, and an older tricyclic antidepressant. The data, he concluded, showed no statistically significant difference between Prozac and placebo in the rate of suicidal acts or thoughts. Striking a chord with Leber and many of the other psychiatrists in the room, Tollefson concluded, "It is our feeling that the major public health concern relative to suicidality and depression is the current stigma, underrecognition and undertreatment of a very serious disease." In other words, it was not Prozac the FDA should be concerned about, but the legions of untreated Americans with depression.

  As Teicher watched Tollefson throw up slide after detailed slide, it struck him that the Lilly scientist had neglected to mention what he himself saw as a major flaw in the Prozac trials: it was very difficult to pick up suicidal side effects because the measurement used-the Hamilton depression scale-wasn't sensitive enough to differentiate between occasional fleeting suicidal thoughts and constant preoccupation with killing oneself. Only one question on the Hamilton scale, question 3, asked about suicidal thoughts, and question 4 inquired about actual suicide attempts. During the discussion period a little later, Teicher saw an opportunity to make that point. He noted that one patient he knew of in the Lilly-sponsored trial had "started out with a three because she had some very, very mild suicidal thought." "Then," he said, "during the course of treatment [with Prozac, her suicidal thoughts] became obsessive and unrelenting but [she] still scored a three; it did not go to four [the code for an actual suicide attempt]." So researchers using the Hamilton scale may simply not have picked up many instances of suicidal thoughts and behaviors short of actual suicide attempts. "The Hamilton item itself ... is a very coarse instrument," Teicher concluded. "That may be a problem in really interpreting those data"

  Tollefson dismissed that idea. He noted that the Lilly researchers had also looked at other indices of depression, and none of them showed any "deviant results." Before Teicher could respond, Leber jumped in and changed the topic.

  Only later would Teicher discover that Tollefson had also omitted from his talk that day information that would have been even more damaging to Lilly's defense of Prozac: One of the company's international clinical trials had indeed shown an increased r
isk of suicidal acts among patients taking Prozac (as compared to placebo). After seeing this data in 1984, the German regulatory authorities had declined to approve the drug's use. (When Prozac was finally approved in Germany six years later, it came with a clear warning that it could cause problems and that it might be necessary for physicians to coadminister a sedative to prevent the agitation and suicidal behaviors sometimes caused by the SSRL)

  Teicher understood that Eli Lilly had a lot riding on the advisory panel's decision that day. But he had no idea how much. No one did, not even Lilly. How could anyone predict that Prozac would soon be one of the bestselling drugs in pharmacological history? By the end of the decade, the drug would inspire several books, a Newsweek cover story, even lyrics to a song; and it would reap Eli Lilly annual sales of $2.6 billion. Lilly was not the only company that stood to benefit from the FDA's support that day. Zoloft, an SSRI manufactured by Pfizer, was on the verge of being approved by the FDA. (The federal agency would give Zoloft the green light in December 1991.) SmithKline Beecham (the company that later became GlaxoSmithKline when it merged with Glaxo Wellcome) had already submitted its application for Paxil, and the FDA would approve that too, in late December 1992. Pfizer and SmithKline thus had a vested interest in Prozac's surviving its first serious challenge.

  Late in the day, there was one effort to turn the tide. Dr. Ida Hellander, a young physician from the Public Citizen Health Research Group who had been invited as a consultant, spoke up. She said she was very disappointed that the panel had not heard much from the three researchers-Teicher, William Wirshing of Los Angeles, and Robert King of Yale, who had reported the most cases linking Prozac and suicidal thoughts and behavior. Wirshing and King had not been invited to the hearing. But, Hellander continued, "Teicher is here and I would really appreciate it if he could have a few moments to talk."