Paxil is Forever

doctor please, some more of these

In a year of tumbling stock prices, accounting scandals, and shaky consumer spending, the British pharmaceutical giant GlaxoSmithKline has had remarkably good news to report so far. More than eight million prescriptions have been written for Advair, its asthma medication, in the year and a half it has been on the market; Trizivir has become the most frequently prescribed drug for new HIV patients; and despite competition from a new generic version, the antibiotic Augmentin is still selling well.

But it is the antidepressant drug Paxil that seems to be GlaxoSmithKline's unstoppable star. During the first half of this year, the drug's sales were up 18 percent in the United States. Every day an estimated 3,000 to 5,000 Americans begin taking Paxil. In 2001 alone, 25 million new scripts were written for the drug. Paxil's strong sales--$2.1 billion last year--are often cited by Wall Street analysts as one reason GlaxoSmithKline's stock remains an attractive prospect in an otherwise gloomy market.

Indeed, during the past 15 years the antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, have revolutionized mental health care. And for tens of millions of Americans, Paxil and its pharmaceutical cousins--Prozac, Zoloft, Celexa, and Luvox--have proven a godsend. They boast far fewer side effects than their predecessors and it's virtually impossible to take a lethal quantity of the new pills. Most people know someone who has been on one of the drugs for years.

Diana Watters

The SSRIs have been a boon to the pharmaceutical industry, too, becoming the third most commonly prescribed type of drug, with sales of more than $13 billion a year worldwide. A bonus: Many patients use SSRIs for years, which takes some of the sting out of the cost of bringing a new prescription drug to market.

For years Eli Lilly's Prozac was the most widely prescribed SSRI. Pfizer's Zoloft has likewise taken a turn as the top seller. But it's Paxil that has shone as a marketer's dream. When the drug was introduced in 1992, the market seemed so saturated with antidepressants that it was hard to imagine Paxil would ever catch up. A decade later, it's poised to become the world's best-selling SSRI. GlaxoSmithKline has steadily and energetically added to the list of disorders Paxil can be used to treat, and spent billions of dollars to make sure the buying public knows where to turn in case anxiety or melancholy sets in.

Unfortunately GlaxoSmithKline leaves out one little detail: For thousands of people, it seems that Paxil could well be addictive.

 

The chemical serotonin is present throughout the human body. Among other places, it exists in blood, in the mucous membranes of the gastrointestinal system, and in certain kinds of tumors. Serotonin plays a vital role in regulating sleep, appetite, sensory perception, body temperature, pain, and mood.

In the brain, serotonin acts as a neurotransmitter, a chemical messenger that facilitates communication between two nerve cells. Serotonin molecules are released from a "sender" cell into the space between nerve cells known as the synapse. From there, they are scooped back up by a "receiver" cell.

When physicians describe depression as an illness resulting from a chemical imbalance in the brain, one of the possibilities they speak of is an interruption in the supply of serotonin in the synapses. Perhaps too little of the chemical is being manufactured, for instance, or too little of its chemical precursors--the molecules used to make the neurotransmitter. Sometimes there aren't enough receptor sites, and sometimes serotonin is taken back up before it can get to those sites.

Research into serotonin's role in mood disorders has been going on for decades. Physicians have long known that in many instances, depression is caused by a lack of another chemical important to brain function, norepinephrine. Perhaps, they posited, a lack of serotonin somehow caused or allowed a dip in norepinephrine. If that were the case, the manipulation of serotonin levels would indirectly raise norepinephrine.

Before Prozac came on the U.S. market in 1988, depression was often treated with a class of drugs known as tricyclic antidepressants. These drugs were quite effective at manipulating both serotonin and norepinephrine but caused a wide range of bothersome side effects.

"In the old days, the pre-Prozac days of tricyclic antidepressants, you were told to treat endogenous depressions for six to 12 months and then to taper off," explains Kevin Turnquist, a psychiatrist with the Hennepin County Mental Health Initiative. "In most cases, it worked well for those people; in fact, the tricyclics worked slightly better. The problem was the side effects. A week's dose was lethal."

As a consequence, tricyclics were not widely prescribed. The advent of Prozac, Paxil, and the other selective serotonin reuptake inhibitors changed that. Although each is a slightly different chemical cocktail, the SSRIs all work in roughly the same way: They slow the action of brain cells that take serotonin out of the synapses, raising the amount of the chemical circulating in the brain. And they do it with relatively few side effects. "Plus," notes Turnquist, "you could just give one dose, start a patient on 20 milligrams and let them stay on it. It's much easier and safer for the doctor to prescribe."

To gild the lily, the pharmaceutical industry touted the SSRIs as non-habit-forming. "Paxil is not a controlled substance," explains GlaxoSmithKline's promotional literature. "Paxil belongs to a class of medications called SSRIs, which have not been shown to be associated with addiction." The claim is repeated in all of the ads for Paxil, and in the drug information GlaxoSmithKline gives to doctors.

Kevin Murphy found all of this information comforting when he and his wife struggled with the decision to put their 11-year-old daughter Kelly on medication. She'd been having panic attacks for a while and had tried several kinds of therapy. Nothing worked, so the Murphys, who live in Lino Lakes, swallowed their concerns and took Kelly to see a psychiatrist. "He prescribed a couple of medications that didn't do anything," Kevin Murphy recalls. "He switched her over to Paxil, and Paxil worked pretty quickly.

"We had talked to the doctor and said what we'd really like to do is have her on it for a year and then take her off of it in the hope that her body would have unlearned the panic response," he continues. "As we drew near the end of that year, her doctor said very casually that it's always a good idea to taper off of this very gradually. She was already cracking a 10-milligram tablet in half, then she started cracking that in half, too, to get to 2.5 milligrams.

"Finally, she was off of it altogether for a couple of days and then she started to have panic attacks. Her heart would just race, and then she'd think she was going to be sick--and she hates being sick. So we called the doctor, and he said to put her back on it."

For the next three-plus years, they tried other tactics for weaning her off the drug. They tried switching her to Celexa, another SSRI. That failed. They tried the same tactic, but using Prozac. They tried anti-nausea drugs, acupuncture--"everything," Murphy says, "but nothing helped."

In addition to excruciating stomach pain, Kelly was so nauseated she couldn't sleep or eat. Doctors examined her upper gastrointestinal system. She had a CT scan, an ultrasound, and countless other tests. Each showed her to be healthy. And yet each time she stopped taking Paxil, she found herself homebound. And each time, she went back on Paxil--at a higher dosage.

Kelly's mother, Maureen Murphy, was forced to quit her job to stay home with her. She missed months of school. "We had to get a tutor for her so she wouldn't fail school," Kevin Murphy says. "She lost 10 pounds. She would be up until 1:00, 2:00, 3:00 a.m. trying to sleep.

"And all the while her psychiatrist said, 'This is really weird. I'll check with the drug company and see what's going on.' And they told him that nothing like this happens with this drug," he recalls. As for Kelly, he adds, "She told me several times she wished she were dead."

Right now she's trying one more time to taper off Paxil. On the advice of a psychiatrist, she switched to a liquid form of the drug so she could decrease her dose by one milligram each month.

Last fall, Murphy became one of 34 named plaintiffs in a class-action lawsuit filed in U.S. District Court in Los Angeles. Since then, some 6,000 people have joined the suit. Several other law firms are pursuing similar suits in the United States. In addition, suits have been filed in Canada (in British Columbia, Ontario, and Quebec) and in England.

 

In 1992, when Paxil hit the market, it faced a seemingly uphill battle to wrest customers from older SSRIs such as Prozac and Zoloft. The U.S. Food and Drug Administration had approved Paxil for the treatment of depression, like those drugs. But its manufacturer, SmithKline Beecham (because of a 2001 merger, now GlaxoSmithKline), was more interested in positioning Paxil as a remedy for anxiety disorders.

Before SSRIs, anxiety had been treated mostly with psychotherapy. In the most serious cases, psychiatrists turned to Valium and other benzodiazepines--again, drugs with a host of serious side effects. Just as Prozac had revolutionized the treatment of depression, SmithKline promised to change the treatment of anxiety disorders by providing a safe alternative.

The company quickly secured permission to market Paxil for the treatment of panic disorder and obsessive-compulsive disorder. By mid-1995, Paxil had become the fastest-growing SSRI in the United States. In 1996, sales of the drug had climbed 54 percent to $291 million.

Impressive though those numbers may be, SmithKline was on the verge of a much bigger marketing coup: The company had been working to win approval from the U.S. Food and Drug Administration to market Paxil as a treatment for the first of a series of little-known mental health ills. In 1999, the FDA agreed to allow Paxil's prescription for the previously rare "social anxiety disorder."

SmithKline hired a New York public relations firm to raise awareness about the syndrome. According to the trade journal PR News, Cohn & Wolfe "developed a plan to educate reporters, consumers, and, in some cases, physicians, in an effort to encourage diagnosis and treatment."

All indications are that the agency earned its fee. "Paxil's reintroduction secured nearly 1.1 billion media impressions in 1999, with 400 million generated in the month that the drug was granted FDA approval," raved PR News. "Media highlights included the cover of U.S. News and World Report, The Howard Stern Show, Parade, National Examiner, the New York Times, Good Morning America, and Vogue. Ninety-six percent of media coverage delivered the key message, 'Paxil is the first and only FDA-approved medication for the treatment of social anxiety disorder.'"

Earlier studies had suggested that perhaps two percent of the population suffered badly enough from social phobia to warrant treatment. Far worse than simple shyness, these people harbored "persistent irrational fear and the need to avoid any situation in which one might be exposed to scrutiny by others and potentially embarrassed or humiliated," according to one medical dictionary.

Following SmithKline's PR and advertising campaigns, however, sufferers were presenting themselves for medication in record numbers. "Paxil sales surpassed those of Zoloft," PR News reported, "and tied those of Prozac for the first time in history, and the Social Anxiety Disorder Coalition received nearly 12,000 calls to its 800 number."

A support group funded by the pharmaceutical industry, the coalition recruited patients to share their sagas with the media. Donny Osmond--diagnosed with the condition by the head of one of the coalition's member groups--recounted his struggles with the disorder on network television. "Never underestimate the power of a celebrity to invigorate a tired media story," observed PR News. A few weeks later, PR News recognized Cohn & Wolfe's campaign with its Platinum PR Award.

"Every marketer's dream is to find an unidentified or unknown market and develop it," Barry Brand, SmithKline's product director for Paxil, told Advertising Age. "That's what we were able to do with Paxil."

Last year, GlaxoSmithKline won FDA approval to sell Paxil for generalized anxiety disorder, a diagnosis that was created by psychiatrists as something of a catchall entry in the Diagnostic and Statistical Manual of Mental Disorders. Sales shot up 17 percent to $2.1 billion. A few months later, post-traumatic stress disorder was added to the list.

SmithKline's so-called public-awareness campaigns were just one half of a coordinated strategy, though. In 1997, the FDA relaxed its rules on pharmaceutical advertising to let the pharmaceutical industry bypass healthcare providers to market its wares "direct-to-consumer" (DTC in marketing shorthand). In 1996, drug companies spent $595 million on advertising. Within a year, spending rose to $843 million. By 2000, the amount had shot up to nearly $2.5 billion.

Paxil was the first central-nervous-system drug to be advertised by name on television, according to Advertising Age. With such tag lines as "Your life is waiting" and "What if you were allergic to people?", the spots targeted 18-to-34-year-old professionals.

In the weeks following the attack on the World Trade Center, Glaxo positioned Paxil as the perfect antidote to post-9/11 anxiety. "Your worst fears," agonized one woman, seated at a kitchen table, "the what-ifs... I can't control it." "I'm always thinking something terrible is going to happen," another woman fretted. "It's like a tape in my mind," a third confessed. "It just goes over and over and over."

"DTC is a great way to create demand," the trade journal Drug Topics quoted one marketing VP as saying. "Advertisers are trying to help consumers recognize a specific symptom and then recognize that something can be done to alleviate the symptom."

The ads pay off for drug companies. Ninety-one percent of people surveyed in 2000 by Prevention remembered seeing a drug ad; one third of them then asked their doctor about the medicine. Seventy-one percent of patients who asked for a drug they had seen advertised left with a prescription.

The statistics don't surprise the Mental Health Initiative's Turnquist. "I get phone calls from people who've seen the ads and they may be doing okay, but they say, 'Hey, I want to try this new drug,'" he says. "The patient sees an ad on TV, and there's a smiley, happy face bouncing across the screen, and they aren't feeling that well." It seems like it's worth a try, especially because the drug is billed as harmless.

The FDA's new rules on promotions freed drug companies from listing all of the side effects associated with every drug in every ad, but they still require accurate and balanced information about a drug. Nonetheless, the FDA frequently reprimands drug companies for TV and magazine ads that downplay a drug's risks, misstate its benefits, or wrongly characterize it as better than another.

In November 2000, for example, the agency took Eli Lilly to task for a TV spot for Sarafem, the name given to Prozac when it is sold as a treatment for premenstrual dysphoric disorder (PMDD). "Think it's PMS?" the voiceover asks, as a frustrated woman tries to wrestle a shopping cart. "It could be PMDD." The FDA complained that the ad made no distinction between PMS and the much more rare and serious PMDD; that jumpy graphics distracted viewers' attention from the list of side effects and risks; and that other vital information was listed in type that was all but invisible.

Poor compliance aside, the pharmaceutical industry has begun a campaign to have the FDA's authority over advertising loosened even further. The companies want to use much shorter lists of possible side effects in magazine ads, for instance. Leading the FDA's review of the rules is the agency's chief counsel, Daniel Troy, an attorney with a history of challenging the FDA on marketing issues, including attempts to restrict tobacco advertising.

 

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.

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