This is part two of a 2002 article about Paxil marketing and withdrawal by Beth Hawkins.
Listen to enough people who can’t seem to stop taking Paxil and you start to notice a common thread: When they first ask a doctor about their withdrawal, they all too often hear that whatever they are experiencing, it has nothing to do with Paxil. They are routinely told that any “discontinuation effects” should clear up in a few days. When they are still ill a week, two weeks, or sometimes months later, they may be told that the symptoms signal a return of their depression.
About a year ago, Randi Morrison (not her real name) drove herself to the emergency room. The diarrhea and upset stomach that had been dogging her for weeks just kept getting worse and worse. She’d lost a lot of weight and started having crying jags. Her family was panicked. At the ER, it didn’t occur to her to tell anyone that she’d been weaning herself slowly off Paxil for weeks. And it didn’t occur to the hospital staff that after eight years of taking the drug, she might be addicted. “They first said I had an eating disorder,” Morrison recalls. “The [doctor] asked me if I had a ‘fond liking’ of laxatives. Then she asked me how much methamphetamine I had done that day. No one ever asked me what medication I was on, what else was going on. I think they just drew conclusions.”
When it finally occurred to Morrison, a Brooklyn Park resident, to mention that she had become ill when she began decreasing her Paxil dosage, “they said, ‘then obviously you need to be on this medication.’ And me not knowing it was the medication causing it, I agreed. I felt kind of lethargic for a couple of days, but my stomach problems went away and I stopped–mostly–crying.”
Morrison tried again to quit Paxil in the winter, with the help of her psychiatrist. Again, she spent a couple of months tapering off the drug. But this time the effects were worse than before. “By the time I took the last pill, I was okay for a day or two,” she recounts. “On day three, I was incredibly tired. I had to call in sick to work. I mostly just slept that day. But as the week went on it just turned into a fucking nightmare. One minute I was bawling, the next I was enraged.”
“I remember wanting to stab my mom with a fork,” she continues. “I went to staring at a blank wall and laughing. I had tremors. I would be really hot and shaky at some times, and I was sweating tons and tons of this rancid, metallic sweat. I got these electrical zaps if I turned my head, or even just from eye movement.
“I called the doctor and was told to go back on it and then try tapering off again. I hung up on him. I called pharmacists and they said there was no proof that this stuff even occurred. So I hung up on them.”
A hairdresser with a hefty client list, Morrison quit going to work. “It’s incredibly hard work to make people feel pretty when you feel like shit,” she says. “It was like getting off crack, for chrissakes.”
Tales like Morrison’s don’t make Kevin Turnquist so much as blink. “If you spend an hour online, you’ll know as much about this as the majority of general practitioners,” he says. Indeed, more than 25 percent of psychiatrists and nearly 75 percent of other physicians are unaware that patients might have trouble discontinuing the drug, according to the Harvard Mental Health Letter.
One of the differences between Paxil and its pharmaceutical cousins is its half-life, the length of time the drug takes to leave a person’s system. Whereas Prozac lingers in the body for two to four days, Paxil wears off in about 20 hours. And a short half-life is one characteristic that can make a drug habit-forming. “The brain likes things to change very gradually,” explains Turnquist.
In 1993, five months after Paxil went on the market in the United States, a study presented at the American Psychiatric Association’s annual meeting found that up to 42 percent of individuals suffered withdrawal symptoms when they stopped taking the drug. At the same time, Great Britain’s counterpart to the FDA, the Committee on the Safety of Medicines, reported 78 cases of Paxil withdrawal.
In fact, since 1994 some 16 studies found “withdrawal syndrome” in up to half of individuals attempting to quit taking SSRIs; all the studies noted that the problem was the worst with Paxil. In an Australian study, Paxil caused withdrawal three times as often as Zoloft and four times as often as Prozac. (The second-highest rate of withdrawal is reported with another SSRI with a short half-life, Luvox.)
A Canadian study found that a number of women who took Paxil during the last trimester of their pregnancies gave birth to babies that went through withdrawal. Many of the researchers concluded that the withdrawal symptoms could be mistaken as physical illness or a relapse into depression. Warnings about the withdrawal symptoms were placed on Paxil’s label in several European nations.
Yet, even as the research was suggesting that SmithKline should both change Paxil’s label and work to educate doctors about its withdrawal symptoms, the drug company seemed to be more interested in damage control. For example, in 1997, a report on more than 13,000 British patients’ experience with SSRIs concluded that Paxil was far more likely to cause withdrawal than its competitors. According to a class-action lawsuit filed against SmithKline, the company reacted by ordering its sales representatives to tell U.S. physicians that the damning study had found no difference between Paxil’s withdrawal rates and those of other antidepressants.
The company may, in fact, have known about the withdrawal symptoms much earlier, according to the suit. One hundred and eight patients who dropped out of a clinical trial of the drug told the manufacturer that they had experienced withdrawal. When it reported on the trial to the FDA, the suit alleges, the drug company reclassified these patients as having relapsed. (Typically the FDA uses only the data submitted by a pharmaceutical company when considering whether to approve a new drug.)
The watchdog organization Public Citizen has warned that the FDA is increasingly dependent on the pharmaceutical industry for funding. In 1992, under pressure from AIDS activists and drug companies, Congress passed the Prescription Drug User Fee Act, which allows manufacturers to pay the agency to review products more quickly. The move has cut the average length of time it takes to bring a new drug to market from 30 months to 15. At the same time, however, there’s been an increase in the number of drugs the agency has had to take off the market, according to the Washington, D.C.-based nonprofit.
In May, Congress increased the share of the agency’s funding that comes from drug companies. The provision was neatly hidden in a rider to the $3 billion Bioterrorism Preparedness Act. Sen. Ted Kennedy, author of the rider and head of the Senate Health, Education, Labor, and Pensions Committee, failed to hold a hearing on the controversial law. The pharmaceutical concerns did have to make one small concession: Recognizing that the FDA was ill-equipped to track drugs once they had hit the market, Congress ordered that some of the fees be used to monitor new drugs.
The wing of the agency that tracks adverse drug effects operates with a shoestring budget of $15 million and a staff of 72 and depends on voluntary and unreliable reporting by doctors, according to a May 2000 article in Washington Monthly. By comparison, the portion of the FDA that approves and monitors new drugs has some 1,300 employees and a budget of roughly $290 million.
It’s a far cry from the systems other countries have in place to monitor the safety of new and popular drugs. “What the Brits and the Aussies do is ask healthcare professionals to pay particular attention to possible adverse effects of both new drugs and those that are widely distributed or they are interested in,” says Larry Sasich, a research pharmacist with Public Citizen’s Health Research Group. “And they give healthcare professionals a lot more information, via a newsletter, for instance….Of course, gathering data is certainly easier in countries with national healthcare systems, because prescriptions can be tracked.”
Last December, nine years after Paxil came on the market, the FDA ordered GlaxoSmithKline to begin warning consumers that they might have trouble discontinuing Paxil. Ever PR-savvy, the company rewrote the label to note that the drug sometimes causes “discontinuation effects.” Even as it was drafting the warning, GlaxoSmithKline argued that Paxil isn’t addictive. In the company’s view, in order for a substance to be deemed addictive it must cause withdrawal symptoms that produce “drug-seeking behavior.” And who ever heard of someone jonesing badly enough to steal Paxil from their neighborhood drugstore?
Nonetheless, on August 16 Mariana Pfaelzer, the federal judge hearing Murphy’s and Morrison’s case, ordered GlaxoSmithKline to stop advertising Paxil as non-habit-forming.
“We are very disappointed in the ruling,” said David Stout, president of U.S. Pharmaceuticals at the company. “The U.S. Food and Drug Administration–and not the courts–has the expertise and responsibility for reviewing and regulating pharmaceutical ads.” The company had submitted the ad in question to the agency for review, he noted, and heard no objections.
“GSK is strongly behind the safety and efficacy of Paxil,” he continued. “Physicians’ organizations like the American Psychiatric Association have stated that antidepressants are not habit-forming. It is also important to note that the court has made no finding that Paxil is addictive or induces dependency.”
The company contacted the FDA, and two days later the agency demanded that the judge lift the ban, arguing that the court had no authority to order GlaxoSmithKline to pull the ads. The agency wanted to reserve that power for itself. Last week, Judge Pfaelzer reversed herself and allowed the company to continue airing the ads.
In 1994, Jessica Porter (not her real name) went to see her nurse practitioner for a checkup. She had lost a lot of weight, and on being quizzed by the nurse she admitted that she was depressed and anxious. “I was in a somewhat desperate space,” she recalls. “I was really unhappy and I felt like I was wasting a lot of my life.”
The nurse suggested she try Paxil. Porter was quick to agree. “I had sort of had it in the back of my mind,” she says. “I just never felt like I was sad enough to seek out therapy.” The nurse gave her a prescription for a supply of 20-milligram tablets and a pill cutter. Porter was to start out taking 10 milligrams and work her way up to 20. If she had a particularly hard time, she could increase her own dose to 30 milligrams. “It had a decent effect,” she says. “It put a floor underneath me. With the drug I still had down times and anxious times, but they were never as bad.”
Porter stayed on Paxil for three years before she started having stomach problems. By that time, the nurse she had been seeing had left her practice, and Porter didn’t feel like she could call the psychiatrist who had renewed her prescription during brief annual visits. So she just quit taking the pills on her own. After a couple of days, she began to feel electrical shocks in her head. “Every time I turned I would have these zaps,” she says. “It felt like I had blacked out for a few seconds.
“I was feeling really bad, and feeling really anxious about feeling bad,” she says. “I was thinking, ‘This is me. This is what I’m like without any drug. How can I live like this?’” She called the psychiatrist and was told to go back on the drug and begin tapering off five milligrams at a time.
After she took her last pill, however, the symptoms returned. “I sought out a therapist, but I was having so much trouble with crying that she said, ‘We need to get you on something and then we can talk.’” She went back to the psychiatrist, who put her on Prozac. The doctor assured her she’d be able to stop taking the new medication if she wanted to quit.
Porter has grown used to the idea that she’ll take an antidepressant for the rest of her life. “Still, I always have the feeling that I ought to be able to do this myself,” she confesses. “My issue about it is sort of feeling guilty about it. Like, I have a good life. I have this, I have that, I should be able to get through this.”
Porter does have one major cause for remorse, however. A onetime poet, she has stopped writing and she’s sure it’s because of the antidepressants. She can’t articulate why she can’t create while she’s on medication, but she has accepted it as an inevitable side effect.
If Kevin Turnquist were to meet her, this part of her story would probably trouble him the most. He has a theory that a lack of novel experience–good and bad–puts unhealthy stress on the human brain. “Mundane jobs, boring routines, and the absence of real struggles for survival may all prove to contribute to depression’s increasing place in society,” Turnquist wrote recently in The Humanist. “We cannot discount the possibility that the activities that seem to add diversity to our modern existence don’t provide the sort of stimulation that healthy brains thrive on.”
The latest research indicates that there is a connection between the size of the piece of the brain involved in the formation of memories, the hippocampus, and depression. “One study suggests that the hippocampus may shrink by an average of 19 percent in depression,” Turnquist reports. “Other research has found that SSRI antidepressants and shock treatment, among other factors, restore the hippocampus to more normal volume. This increase in the size of the hippocampus is now considered to be a possible mechanism by which these treatments promote recovery from depressive illness.”
In Turnquist’s experience, many of the people who have a hard time quitting SSRIs are young women. Many didn’t respond well to the drug in the first place. “What you never see are studies about the characteristics of the people who have trouble getting off of this medication,” he says. “My guess is that these are people with chronic, low-grade depression. A lot of them have had awful childhoods. Some have been abused. One of the effects of an abusive childhood is a smaller or misshapen hippocampus.
“The drug companies work like crazy to keep them out of their studies,” he continues. “When you look at the entrance requirements for these trials, they don’t want people who are suicidal, they don’t want people with long-term depression. They want people with nice, circumscribed depressions. They don’t want people who are going to sue them.”
Nor is GlaxoSmithKline likely to pony up to fund research into Turnquist’s theory. After all, a prescription to do something new and stimulating–to exercise, travel, or turn off the TV–isn’t going to do anything for the price of the company’s stock.