On a Friday afternoon last month, Dr. Joseph Glenmullen, author of "Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Effective Alternatives," left his office at Harvard University Health Services to visit New York. While he was away, two men from Eli Lilly & Co., the pharmaceutical company that produces Prozac, paid his office an unscheduled visit. Given what Glenmullen writes about the drug, he assumed they weren't there for his autograph.
Eli Lilly maintains that the visit was a routine sales call to the clinic. One of the representatives even left a card. But whatever the reason for Eli Lilly's call, the Indianapolis giant has loomed large in the psychiatrist's life since his harshly critical look at the long-term effects of antidepressants was published April 5.
Lilly representatives and other critics have slammed the book as misleading and lacking in scientific rigor. A company letter to an Indianapolis reporter called it "the work of a storyteller, not a scientist" and concluded that it was "a fear-mongering publication." The book has also grabbed the attention of ABC's "20/20," which interviewed Glenmullen and Eli Lilly representatives for a segment on antidepressants. The segment, taped last month, has yet to air. Some speculate that the delay is linked to the network's relationship with Lilly, which has been a prime-time advertiser on ABC since early April when the book was released.
Glenmullen argues that his critics' objectivity is tainted by the fact that many of them receive money from Lilly. But even some researchers who have no connection with Lilly -- who have, in fact, been harsh critics of Prozac and other antidepressants -- have problems with Glenmullen's book. Two major researchers have accused him of simply recycling their ideas without acknowledgment.
Glenmullen is a 49-year-old Harvard Medical School graduate and untenured clinical psychiatry instructor at Harvard University. He says he first noticed the side effects of antidepressants on his patients in private practice 10 years ago, but his research on the subject has never appeared in any medical journal.
His 338-page book, begun in 1996, relies on dozens of studies from medical journals, magazine articles, FDA documents and Glenmullen's own clinical experience to chronicle the dangers of Prozac-type antidepressants and suggest alternative therapies.
Some of the side effects he enumerates -- sexual dysfunction, weight gain and tremors -- have been well documented. "The fact is that any drug, and certainly all of the antidepressants, have side effects," says Dr. Harvey Ruben, the director of continuing education for the department of psychiatry at Yale University.
What has raised eyebrows is Glenmullen's statistics. "Prozac Backlash" says that the selective seratonin reuptake inhibitors, or SSRIs, in Prozac lead to sexual dysfunction in 60 percent of all users. Prozac's packaging, by contrast, asserts that that 2 to 5 percent of users will suffer such problems. (Eli Lilly now maintains a figure in the 20-30 percent range and plans to update its literature.)
Glenmullen also suggests another long-term side effect of antidepressants: suicide. He estimates that between 1 and 3 percent of his patients became suicidal on antidepressants, a percentage experts consider serious. He also believes Eli Lilly has suppressed this information.
The Boston Globe recently published an internal Lilly document that revealed that the company was aware that akathisia -- a severe agitation that can lead to suicide -- occurs in at least 1 percent of users. It also mentions that the patent documentation for a new version of Prozac, R-fluoxetine, says the update will not produce such existing side effects as suicidal thoughts, self-mutilation and akathisia (listed as "one of [Prozac's] more significant side effects" in the patent). The patent is assigned to Marlborough, Mass., pharmaceutical company Sepracor, which will co-produce the drug with Lilly.
Lilly, however, claims that the Food and Drug Administration gives Prozac a clean bill of health in that regard. "In 1991, a panel of experts appointed by the FDA found no credible evidence of a causal link between the use of antidepressant drugs, including Prozac, and suicidal or violent behavior," the company said in a statement. The FDA still stands by its conclusions.
An estimated 28 million people in this country, almost one in 10 Americans, use antidepressants. Not surprisingly, Glenmullen's claims have caused a huge uproar in the mental health community: If his figures are correct, nearly 17 million people suffer from SSRI-related sexual dysfunction.
Yet Glenmullen does not advise patients to stop using SSRIs. "I'm not a Prozac foe," Glenmullen told Salon. He claims he harbors no animus against either the drug or Eli Lilly, but only for doctors who use Prozac as a panacea. "I'm a foe of it being over-prescribed, used trivially, and of patients not being warned of side effects or offered alternatives." He advocates the use of antidepressants for patients with moderate to severe symptoms. He does, however, suggest that patients with mild depression consider other alternatives, such as St. John's Wort (an herbal remedy that itself has recently been under siege for its lack of conclusive effect).
The new criticism of Prozac comes at an awkward moment for Eli Lilly. Though Prozac remains the company's bestselling drug, it has encountered declining sales over the past year largely because of increased competition from rival drugs such as Zoloft, manufactured by Pfizer. In the first quarter of 2000, Prozac sales rose a scant 1 percent to $596.2 million. (Despite anemic sales growth, the figure represents roughly a quarter of Eli Lilly's total revenue, an extraordinary sales percentage for a single product.) With Sepracor, Lilly plans to market R-fluoxetine before Prozac's patent runs out in 2002.
Eli Lilly marketing and communications associate Laura Miller notes that her company initially became concerned when Glenmullen claimed, in the publicity package from the book's publisher, Simon & Schuster, that antidepressants "may effect a chemical lobotomy." But Eli Lilly refuses to respond to any specific charges in "Prozac Backlash."
"It's full of anecdotes that will frighten people off their medication," says Miller. "It's a disservice to patients."
The company's official statement on the book is this: "We stand by the safety and efficacy of Prozac ... No one should stop, or start, taking Prozac -- or any other prescription medication -- without physician supervision."
Other mental-health professionals echo Lilly's criticisms. "The truth about depression and its treatment is just the opposite of what the book claims," Mike Faenza, CEO of the National Mental Health Association, writes in his association's PR Newswire. "We're concerned that people may decide against seeking appropriate treatment for this serious illness after hearing about this book."
Tom Richardson, president of the Washington state chapter of the National Alliance for the Mentally Ill, wrote a negative review of the book in the April 14 edition of the Seattle Times. "The book is suggesting we all take St. John's Wort," he says.
NMHA and NAMI both receive significant funds from Eli Lilly, which refers journalists to the organizations for information. NMHA, in Alexandria, Va., receives around $1 million in funding. In its April 11 statement condemning "Prozac Backlash," it describes itself as "the country's oldest and largest nonprofit organization addressing all aspects of mental health and mental illness." It never discloses that Eli Lilly is one of its principal contributors.
"We get some funding from them for public education and advocacy work," says NMHA spokesman Patrick Cody. "The bulk of our money comes from the federal government." When pressed about a potential conflict of interest about criticizing the book, Cody denied that there was a problem. "We're not selling these antidepressants," he says.
NAMI, in Arlington, Va., received $2.87 million from Lilly between 1996 and 1999. Spokesman Bob Carolla didn't see any conflict. "As a matter of policy, we don't endorse or recommend any treatment," he said. Carolla added that the money the association received was for unrestricted education grants.
Eli Lilly also referred journalists seeking medical opinion on "Prozac Backlash" to Drs. Jerrold Rosenbaum and Anthony Rothschild. Rosenbaum, associate chief of psychiatry at Massachusetts General Hospital and a professor at Harvard Medical School, serves on Eli Lilly's board of advisors, as well the boards of several other pharmaceutical companies. He explains that they only pay him to visit them for a day or two and cover his expenses. "With psychopharmacology, this is unavoidable," says Rosenbaum. "I have a strong conflict of interest. This is my life." (Rosenbaum, who discloses his position freely, adds that he asked Lilly to stop giving out his name as a critic of the book.)
Doctors are bound to disclose their affiliations when they submit an article to a medical journal, or when they deliver a speech. But if a reporter wants to know if a physician is on an advisory board, or if he or she is being paid by a pharmaceutical company, the reporter must ask. When it comes to a physician's motivations for supporting or slamming a book, lack of disclosure has become a prevalent problem. "This is becoming very common. It's difficult to see who's being supported," says Nicholas Regush, a medical reporter at ABC who also writes a medical column for abc.com.
According to some, accusations from paid critics are standard procedure in medical publishing. Dr. Peter Breggin, author of "Talking Back to Prozac: What Doctor's Won't Tell You about Today's Most Controversial Drug," calls Eli Lilly "the stormtroopers of the drug industry," adding that MNHA and NAMI "are in the pocket of Eli Lilly." Breggin, who has been an expert witness in several lawsuits involving antidepressants, said that the company "tells untruths about their critics." Though he was paid by various states for his testimony, he claims he was not compensated by a pharmaceutical company for his services.
Thomas J. Moore, a medical researcher who helped Glenmullen with the book, said he himself has been the target of Eli Lilly campaigns to tarnish him. He's not surprised by the reception to Glenmullen's book. "If you publish material like that, you'll be discredited."
As troubling as these conflicts sound, they are still distractions from the central issue: Glenmullen's research and his credibility. Indeed, Glenmullen's credentials have been called into question. Skeptics wonder why he never published in any medical journals. Rosenbaum told an Indianapolis Star reporter than in the decades of his Harvard affiliation, he had never heard of Glenmullen, an observation that has been echoed by Eli Lilly.
"I'm especially qualified," Glenmullen responds, "because I'm someone whose research is not funded by pharmaceutical companies."
But other experts who claim no affiliation with Eli Lilly are also skeptical, if not infuriated. "When you take all the side effects the author claims can occur, it sounds like it's the worst agent ever made for man," says Yale's Ruben. "I hope that this book doesn't have wide popularity because it frightens people who are on the medication and doing well with it."
Ruben is also skeptical about conflict-of-interest claims. "All the major researchers are on the boards of major scientific companies," he observes. "The companies need people they don't own to advise them on their drugs. They aren't paying a huge amount to anyone."
Right now, criticism may be the least of Glenmullen's problems. Aside from the charges that "Prozac Backlash" is "anecdotal" -- a derisive way of saying that the book lacks scientific rigor -- some doctors have charged that Glenmullen used their work out of context, or worse, did not credit them.
In a statement distributed by Eli Lilly, University of Massachusetts professor of psychiatry Dr. Anthony Rothschild claims that the book is "misleading" and observes that "Dr. Glenmullen bolsters many of his own arguments and proves his hypotheses by borrowing liberally from others' work, including my own." According to Glenmullen, Rothschild also has ties to Lilly (Rothschild did not respond for comment).
Dr. Peter D. Kramer, author of "Listening to Prozac," says that Glenmullen "grossly misrepresents me" and "uses me as a straw man." Glenmullen, however, disagrees. "Dr. Kramer seems to be confused with the message of his own book," he says.
Breggin makes a more startling accusation: "To a great extent, he simply takes ideas that I developed in two or three other books, doesn't credit them, and cites new sources to confirm them. He takes an area in which I have been a central figure for 12 years and acts like I don't exist."
Glenmullen responds that "'Prozac Backlash' is coming out six years after Dr. Breggin's book and goes way beyond it."
Simon & Schuster dismisses the plagiarism accusations. "We stand behind the book 100 percent," says S&S publisher David Rosenthal.
To make matters worse, some suggest Glenmullen is simply courting controversy to stir up sales. His critics have mentioned that, as a clinical instructor, Glenmullen isn't paid. And being a part-time doctor at Harvard's health services isn't likely to be especially lucrative. Glenmullen, who also has a private practice, dismissed the speculation, saying that it doesn't address the research in his book.
But critics like Rosenbaum see cynicism, even in the title of Glenmullen's book. "His publisher is exploiting this issue," says Rosenbaum. "If this book were called 'SSRI Backlash,' it wouldn't sell."
As Eli Lilly tinkers with Prozac 2.0, the pharmaceutical company continues to advertise for Prozac on network television. Lilly ran a glossy prime-time ad campaign for Prozac on ABC early last April. Around the same time, "20/20" began shooting its investigative segment on the side effects of antidepressants. ABC would not provide a broadcast date. "We don't schedule until a day or two in advance," says ABC spokeswoman Dahlia Roemer.
The FDA has not done a comprehensive study of Prozac since its report nine years ago that ruled out any connection with suicide. Spokeswoman Susan Cruzan explains that the agency is on top of the problem. "It's looked into all the time. We inspect companies every two years," she says. "Pharmaceutical companies are obliged by law to report the side effects of their drugs to the FDA; part of the agency's inspection includes an examination of how the company keeps their records."
The FDA also monitors MedWatch, a program that allows professionals and patients to report any negative side effects. In other words, the FDA may be vigilant, but hardly proactive in this particular issue.
Meanwhile, unlike Glenmullen's medical critics, the mainstream press is welcoming the book with open arms.
"In Glenmullen's view, 75 percent of people on SSRIs can either go off the drug or dramatically reduce their dose. In any case they should read this book," concludes the New Yorker.
"While his accounts of his own experience with patients is helpful, Glenmullen's most valuable contribution is his reporting on what little monitoring has been done," Publishers Weekly points out.
While the side-effect controversy continues to play out, the story has the unintended consequence of making Elizabeth Wurtzel appear prescient. Her 1993 bestseller "Prozac Nation" provides the following wisdom: "I can't help feeling that anything that works so effectively, that's so transformative, has got to be hurting me at the other end, maybe sometime down the road."
Shares