Inside the Happiness Business

Dr. Ronald A. Ruden practices medicine in a suite that resembles a vast underground hangar, below a high-rise on the Upper East Side. His waiting room is furnished with small café tables and colorful Macintosh computers, so idle patients can surf the Web. Ruden and his partner run one of the largest practices in the city. He personally sees nearly 200 patients a week, compared with 50 for most doctors, he says.

Ruden is an internist, not a psychiatrist, but on top of his bustling practice, he managed in his spare time to publish a book, The Craving Brain, sketching out some unconventional ideas about the roots of addiction. He is also an enthusiastic prescriber of antidepressants.

A few months ago, a woman who works in his office – I will call her Heidi – came to Ruden seeking help. A middle-aged immigrant, Heidi told him she had always been a worrier. Recently, though, her anxiety had risen to a new pitch. She found herself rechecking minor tasks three or four times to be sure they were done. Sometimes at home in her apartment in Queens, she grew so nervous that her heart raced; she’d board a bus back to the office just to make sure that everything was in order.

After a brief consultation, Ruden stepped into the hallway, reached into a cabinet, and took out some bulky blue-and-yellow cardboard packets labeled CELEXA.

Only two years ago, no one in the U.S. had heard of Celexa. But since its launch in September 1998, it has captured over 13 percent of new prescriptions in the $6.3 billion market for its class of antidepressants, which also includes Prozac, Zoloft, and Paxil. And Celexa is the only one whose market share is growing.

“You may have reason to wonder: Is your doctor doing what’s right for you, or for him?”

The drug has achieved this spectacular growth without any decisive advantage over its predecessors. “With these antidepressants,” says Ruden, “you have to understand that we really don’t know what we are doing. We know these drugs work, but we don’t know exactly how, and each one is a little different.”

The reason for Celexa’s stunning success is not science but marketing. Drug-industry consultants Scott-Levin say U.S. pharmaceutical companies spent about $10 billion last year on drug promotions. Most of that – $9 billion – went toward marketing to doctors (about $12,000 for each doctor in the U.S.). Drug makers command an army of more than 68,000 salespeople, one for every eleven doctors in the U.S. While pharmaceutical companies justify high drug prices by pointing to astronomical research and development costs, many who study the industry say drug companies spend more on marketing and promotions, especially for drugs like Celexa.

Celexa is what is known in the business as a “me-too” drug. The Medical Letter, a nonprofit newsletter that evaluates new drugs, pronounced that Celexa had “no advantage” over Prozac, Zoloft, and Paxil. All adjust the level of serotonin in the brain. All four improve the mood of about 65 percent of the moderately depressed patients who take them.

Ruden has been prescribing Prozac for years. “A familiar drug gets to be like an old friend,” he says. He is on good terms with Ashleigh and Julie, the Prozac drug reps who visit him from Eli Lilly & Co. Like other busy doctors, Ruden is showered with small gifts and invitations to events at fancy restaurants. Once, a sales rep called to invite him and his wife to a Yankees game. Ruden told her, “Look, just give me the tickets,” and he took his family instead. There are so many new drugs appearing all the time, Ruden says, that he has to rely in part on the drug salespeople to keep him up-to-date. But he says he threatens them if they aren’t forthright: “Tell me the warts,” he warns them. “If I prescribe something, and its wrinkles – its possible problems – catch me by surprise, I will never prescribe your drug again.”

Michelle and Tina, new reps from Forest Laboratories promoting Celexa, filled his cabinets with “a ton of free samples.” They told him Celexa was “the cleanest” antidepressant, with a “favorable side-effect profile.” And they suggested that Celexa may be less likely to bring on Prozac’s most infamous side effect – the tendency to sap the libido and inhibit orgasm.

Ruden was skeptical – he was convinced the whole class of drugs shared that drawback – but he tried the new pills on a few patients. He found that Celexa seemed a little less “activating” than Prozac, which sometimes causes agitation, he says. Heidi took the samples Ruden gave her, and a prescription for one 20-mg. capsule a day. A few months later, Heidi says, Celexa restored her life to normal: “I can relax, watch TV, fall asleep. I thank Dr. Ruden from the bottom of my heart. Actually, I should thank the sales reps, Michelle and Tina, too, next time they’re here.”

Drug sales representatives have been around ever since the Food and Drug Act first created prescription drugs in the twenties. They are known in the industry as drug reps or detailers. (To pitch a drug to a doctor is to “detail” him, in the salesmen’s argot.) The ranks of drug reps have swollen in recent years, from 36,000 in 1994 to 68,000 today, according to Scott-Levin. Although some drug reps hold degrees in pharmacy, medical experience is hardly a prerequisite. Dr. Jon Mohrer, an internist practicing in Forest Hills, Queens, recalls a salesman who walked into his office not long ago and said, “I know you!” Mohrer assumed it was just another play for his attention. But it turned out the salesman had previously served his family as a waiter at a neighborhood pizza parlor. Pfizer, a marketing powerhouse, has earned the industry nickname Semper Pfizer for its policy of recruiting former military personnel and teaching a hard-sell mentality.

Selling drugs to physicians takes quite a bit more training than most sales positions, of course. Forest, for example, runs a three-month training program out of a special campus on Long Island. After “graduating,” sales reps receive monthly packets of information to digest. They are tested over the phone by a computerized quiz system. But it is well worth it. “Pharmaceuticals is a very hard sales job to get,” says René Backer, a star Forest rep and now a regional director who works out of her home in Philadelphia. “It tends to be among the higher-paying sales jobs I can imagine.” She declines to comment on her own paycheck, but other drug reps say that with a good incentive bonus, a successful rep can make $140,000 a year.

The typical drug rep is female, about 30 years old, well dressed, and attractive – picture a Jil Sander suit and a giant suitcase on wheels. Doctors make the acquaintance of their first drug reps within their first month of residency. Reps flood training programs with pens, coffee mugs, stethoscopes, and bags, and are delighted to pick up the tab for all of a student’s textbooks. (The reps stick their companies’ logos inside the covers, of course.) At most hospitals, drug companies also cover the cost of an important part of resident training by sponsoring talks by medical experts, inevitably on subjects related to their products. A rep touting an antibiotic, for example, will pay an infectious-disease specialist a small sum to address surgical residents about transplants, where antibiotics are essential. The rep may even say a few words about her product after the talk.

More often, though, food is the reps’ weapon of choice. They arrange with head residents to cater buffet lunches in clinics. As hungry residents load up their plates, reps buttonhole them to repeat short plugs for their pills’ best attributes, like “lower side-effect profile” or “more digestible.” They beep residents on their pagers to invite them to meals and happy hours. Some hospitals have bulletin boards full of reps’ business cards, so residents can call for a meal whenever they feel like it. “They always try to take you to the fanciest restaurant possible, so they can really lure you in,” says Laura Goetz, a surgical resident at Northwestern Medical Center in Chicago. “It’s viewed as a prostitute-pimp relationship.” The residents make up nicknames for their favorite reps, she says, like “Diflucan Dave,” who hocks an anti-fungal pill, or “Trovan Tom,” who touted an antibiotic that was heavily marketed until it killed six patients by poisoning their livers.

Emerging from an organ-transplant operation into the hallway of her hospital, Goetz recently ran into a familiar drug rep. He quizzed her about what drugs were used in the surgery, and she happily rattled them off. “Thanks so much – you really made my day,” he said, then handed her a $3 Starbucks coupon. “It just makes you feel kind of cheesy,” she says.

If not for a chance meeting, Celexa might never have been introduced in the U.S. The active chemical in Celexa, citalopram, was first concocted by researchers working for the small Danish company H. Lundbeck in 1972, about the time Lilly first synthesized Prozac. But Lundbeck ran into problems in early tests – its antidepressant proved toxic to beagles, because of what turned out to be a problem specific to the canine metabolism. But by the time the mystery was solved, three other antidepressants were heading into the U.S. market. Citalopram went on to become the best-selling antidepressant in some European countries, but Lundbeck missed out on the U.S., which is the biggest market and the only one free of price restrictions. The few compounds that make it to market as viable drugs bring in profits as high as 90 percent of their prices.

In 1995, an investment banker from London happened to visit the office of Howard Solomon, chief executive of Forest Laboratories, a tiny New York drug company. Seventy-two years old, tall, slender, and reserved, Solomon began his career as a lawyer and entrepreneur. He founded a small chain of bowling alleys and invested in Manhattan office properties before taking over in 1977 at Forest, which had been a legal client.

Solomon’s ears perked up when the visiting banker happened to mention Lundbeck, noting in passing that its main product was an antidepressant popular in Europe but unavailable here. Forest doesn’t discover its own drugs, relying instead on licensing compounds from others, and Solomon knew that grabbing even a small piece of the fast-growing antidepressant market could be a windfall.

To Solomon’s chagrin, however, Lundbeck’s executives wouldn’t agree to meet – they’d already been through the mill with U.S. drug companies (both Pfizer and Warner-Lambert had signed licensing deals before backing out). So Solomon resorted to a white lie. He sent a message to Lundbeck’s chief executive, Erik Sprunk-Jansen, that he was going to be in Copenhagen anyway – could he just stop by? Sprunk-Jansen, a polite man, assented.

After a brief presentation at Lundbeck headquarters a few days later, Sprunk-Jansen took Solomon to lunch in the company’s elegant dining room, where Solomon scrambled to build a rapport. He had read every work by the great Danish author Isak Dinesen, he told them. And did he mention that he was the president of the New York City Ballet? Sprunk-Jansen was impressed. Peter Martins, the ballet-master-in-chief of the New York City Ballet, grew up in Denmark. Solomon said Martins was a good friend, and offered to introduce him.

Sprunk-Jansen and his wife later joined Solomon for a ballet performance in New York, and they dined together at Le Bernardin. At dinner, Sprunk-Jansen’s wife used a napkin to calculate the potential profits to be made in the U.S. market. In early 1996, Sprunk-Jansen agreed to take a chance on tiny Forest and license the drug.

It was the start of a flourishing friendship. When Peter Martins choreographed Swan Lake at the Danish Royal Ballet, Solomon bought an entire row of seats for Lundbeck and Forest executives. Afterward, Sprunk-Jansen hosted a dinner party for 50 at his home in Copenhagen. Everything was in black and white for a Swan Lake theme, with a pastry swan sitting on a mirror in the middle of an enormous table. Sprunk-Jansen later invited Solomon to a dinner modeled on Dinesen’s novel Babette’s Feast. “The only thing different is the year of the wine,” Sprunk-Jansen told Solomon.

Finally, with U.S. regulatory approval secure, Forest Laboratories prepared for launch. On September 19, 1998, Solomon strode to the center of the stage at the San Diego convention center, where a crowd of 2,000 drug reps had gathered from around the country. (About 1,100 of them came from Warner-Lambert, which had signed on as a marketing partner.) Part of the San Diego Symphony performed, and peals of electric guitar filled the air.

Every big new drug is launched with such an event – part pep rally, part pharmacology seminar, interrupted by role-playing sessions to practice “verbatims,” or scripts for detailing doctors. But when Solomon took the podium, he added an unusual motivational flourish. Telling the reps that to sell Celexa, they needed to understand depression, he began reading from the recollections of “an author who himself experienced clinical depression.” Some later learned the author was his own son, Andrew. (His book, a study of depression, is scheduled for publication later this year.)

While Howard Solomon was chasing Celexa, it turned out, his son had been afflicted with a melancholy so severe that at times he couldn’t bear to leave his bed. “I will be on medication for a long time,” Andrew Solomon reflected in one of the passages his father read. “Every morning and every night, I look at the pills in my hand, and sometimes they seem like writing in my hand, hieroglyphics saying that the future may be all right and that I owe it to myself to live on and see. I feel sometimes as though I am swallowing my own funeral twice a day, because without these pills I would be long gone.”

“They wouldn’t make a bonus if they didn’t sell Celexa,” sniped an anonymous Zoloft representative. “It was do-or-die for them.”

But Howard Solomon quickly left such somber subjects behind. Celexa, he told the crowd, had become a best-selling antidepressant in other countries because of its “inherent advantages,” not because of its enormous marketing support, which a company Lundbeck’s size couldn’t afford. “But here in the U.S.,” he added, “Celexa is going to be the largest-promoted antidepressant, with the most physician calls and the largest promotional budget, and we are going to be doing it with the most successful sales forces in the industry.” The crowd gave him a standing ovation.

The presence of drug reps wheeling suitcases of small gifts and pills through waiting rooms and hospital corridors is an uncomfortable issue for doctors. “There is a fine line,” says Dr. John C. Nelson, a Salt Lake City obstetrician-gynecologist, a trustee of the American Medical Association, and the group’s spokesman on the issue. “This is America – the land of the free and home of the entrepreneur. In a world where there are lots of similar medications to chose from, there has got to be a way for a drug maker to try to make its voice heard above the fray,” Nelson says. “But if you think your doctor might be influenced unduly by a drug company, then you may have reason to wonder, is your doctor doing what is right for you or for him? Am I prescribing the medicine that is right for you or the medication that bought me the latest trip to Aspen? Studies have shown that I am more likely to prescribe a drug over the next few days after its maker takes me to lunch.”

In 1989, Nelson became concerned about drug companies’ influence after an experience with the new estrogen-replacement patch – at the time, more expensive and less proven than an oral equivalent. “I tried it, but it irritated patients’ skin,” Nelson says. “The reps said ‘Thanks’ and gave me a pen. My partners said, ‘Heck no, that’s more expensive and less proven.’ Then the company took one on a scuba-diving trip and the other on a golf vacation. They both started using it and, to my knowledge, still do.”

Nelson wrote an essay about the experience in the Journal of the American Medical Association, and it sparked a change in the organization’s guidelines to discourage expensive gifts without any medical purpose. The definitions, however, remain broad and subjective.

“The AMA lost a lot of members over the rule, because people think we are too tight,” Nelson says, adding that drawing the right lines in his own practice remains a “struggle.” Recently, Zoloft’s maker, Pfizer, took Nelson to the finest restaurant in Salt Lake City to hear a local psychiatrist talk. “It was a nicer dinner than I could afford myself,” says Nelson, whose family includes a brood of eight kids. “It’s the old question – will you sleep with me for a hundred dollars? For a thousand? Once you accept the gift, you know what you are.”

To begin its sales campaign, years before the launch, Forest recruited a team of twelve bellwether psychiatric researchers to a Celexa advisory board, to help assess the drug’s potential. “You can figure out pretty easily who is an influencer in the area of psychiatry,” says Nefertiti Green, one of Forest’s Celexa marketing directors.

Like all companies, Forest pays each of its board members a small “honorarium” to participate in meetings, covers their travel expenses, and, more important, puts up money to pay for their research as well. Green says the company follows the American Psychiatric Association guidelines – paying doctors about $500 to speak at a local symposium, $1,500 if it is national. Such payments from drug companies have caused controversy, most notably in the case of Dr. Martin Keller, a Brown University professor of psychiatry and member of Forest’s advisory board. The Boston Globe reported that in 1998, out of $842,000 in income, he made nearly $556,000 from consulting to drug companies – none of which he disclosed when he published research about their drugs.

Dr. Steven Roose, a researcher at the New York State Psychiatric Institute, is another member of Forest’s advisory board. “It’s nice to get an honorarium of a couple thousand dollars, or to go give a talk, especially if it is in a nice place – don’t let anybody tell you that the money means nothing,” he told me, sitting underneath a Jasper Johns poster in his small office. “But the honorarium is gone in two pair of Prada shoes and a bag. What really matters is the research – that’s where the deep issues are.”

An academic medical researcher’s career often depends on being able to conduct important large-scale studies, and funding from drug companies can be a big help. Some fret that drug-company funding inevitably alters the course of research. “Sometimes, when research funds are limited, you will go along with drug-company studies that may be very good, but they aren’t what you would do otherwise,” says Roose. “There really is a pharmaceutical-academic complex.” But Forest impressed its experts by going the extra mile. The company agreed to fund a project that its researchers originally proposed – a landmark study of depression in people over 75, known as the “old-old study.” Forest liked the idea because Celexa may have real advantages with very old patients, because of its limited interactions with other drugs. The company is even paying for expensive brain-imaging tests and patient interviews.

“The real way to influence researchers is to let them do a study like this – that is the quid pro quo, the benefit you get from helping them,” Roose says. Of course, every researcher knows that a single lapse in integrity could ruin his credentials, he says. Investigating the effects of Prozac on the heart, Roose happened to discover that it is much less effective than earlier drugs in treating severe melancholia. “I didn’t expect it. It just hit me in the ass. Was I a popular person with Lilly? No. So maybe I wasn’t invited to speak for a while – who cares?” He told Forest that Celexa isn’t so effective against severe depression, either.

Drug makers, of course, don’t tend to publicize views like that. In a Forest press release, its advisory-board members sound like critics in a movie ad. “Celexa will be a friendly drug for the physician to use, and certainly a friendly drug for the patient,” raves Dr. George Alexopoulos of the Cornell Medical School, another leader of the old-old study.

“Did he say that? I would be shocked,” Roose says. “A thoughtful opinion of a drug can’t be reduced to a quip.”

To warm up the market before Celexa’s debut, Forest began with an advance team of nine “medical-science liaisons” hired in August 1998. The liaisons, many with degrees in pharmacy, set out “to form relationships” with the top 200 or so “thought leaders” in psychiatry, another tier of trendsetting researchers and clinicians. Each medical liaison worked on a list of 22 doctors at institutions like Columbia-Presbyterian Hospital in New York and Massachusetts General in Boston.

In the summer of 1998, still months before the official launch, Forest turned to a tried-and-true technique to kick off the Celexa campaign: paying doctors, essentially, to prescribe it. Before the drug’s approval, the “psychiatric thought leaders” on the advisory board had each put about twenty patients on the drug and answered questions about dosage and results. Next, the company added a nationwide test called Early Access to Symptom Evaluation, or ease. About 600 doctors tested Celexa on about five patients apiece. Doctors received $250 for their help, and another $50 a patient for reporting results – a total of about $500. (Participating patients start the drug free of charge.) The tests helped gather extra information about the drug’s effects. Just as important, the tests acquaint doctors with the pill and start some patients on it.

Then Forest’s reps sprang into action. The company picked about 22,000 of the biggest prescribers of antidepressants and hit them with a soft sell. “We went out before the launch period, with just the FDA-approved package insert, no Madison Avenue glossy promotional material,” says John MacPhee, the other Forest marketing director in charge of Celexa. “We said, ‘We’re here because you are so expert in treating depression. Let’s talk about all the pluses and minuses. Let’s talk about the beagle dogs. It’s new. You can get an early experience, if you want to get a jump on a lot of physicians.’ “

Some doctors were wary – medical ethicists caution against trying new drugs without demonstrable advantages, since less is known about their risks. But in their role-playing sessions, Celexa’s reps had rehearsed a ready answer to that objection: They told doctors that millions of Europeans had already taken it. And some doctors appreciate the chance to offer patients the very latest thing. Ronald Ruden, the Upper East Side doctor, says he jumps at such opportunities. “I am an early adopter,” he explains. “I always want to try the newest drug to see how it works.” By the day of Celexa’s U.S. launch, nearly 15,000 U.S. doctors had prescribed Celexa, too.

As Celexa gained momentum, its rivals struck back. Almost immediately, drug reps from rival companies began what is known in the business as counter-detailing. I even experienced some counter-detailing myself. A Paxil rep, speaking on condition of anonymity, cut into Celexa right away: “It’s not a good drug in the first place, and there are more side effects,” she said, adding that she warns doctors that Celexa could cause kidney problems in overdose, alluding to the beagles. (There was a report of lethal overdoses in Sweden, but it was later debunked; a Celexa overdose isn’t dangerous in humans.) A Zoloft rep took another angle: “You know, there have been some data saying Celexa is no better than a placebo.” (This is true but not necessarily relevant, since placebos are often very powerful in relieving depression.) She called back to call Celexa a “me-too” drug (so are Zoloft and Paxil), quote from the Medical Letter, and describe the “tremendous pressure” Forest put on its salespeople. “They wouldn’t make a bonus if they didn’t sell Celexa – it was do or die for them,” she said.

Part of the reason for Celexa’s success may indeed be Forest’s incentive bonuses. “Forest has put more of the emphasis on the incentive side,” says Mark Devlin, a former Forest drug rep who is now a national sales director. As a result, Forest reps have a higher “physician call rate” than other companies, he says, attempting to visit about twenty doctors a day and “actually getting in front of about ten.” (Lilly’s reps, for example, see about eight a day.) But Backer, his fellow rep, insists the “counter-detailing just helps create more noise about Celexa.” The Forest drug reps were armed with plenty of “clinicals” to back up their claims, she says.

Like all drug reps, Celexa’s bury doctors under a blizzard of trinkets bearing their logo – umbrellas, clip boards, even Valentine’s Day bouquets. “We kind of keep up with the Joneses as best we can,” Devlin explains. “The pens, notepads, coffee mugs – that is something that is expected and, quite frankly, appreciated. Doctors ask for it, and we do our best to give them what is expected.”

Naturally, Forest reps provide the usual assortment of lectures, small group dinners, teleconferences, and “stipends” for speaking or participating. They also offer what are known as “clinical sidebars” where doctors can pick up dinner at a restaurant to take home to their families. “You can have reasonable entertainment, something that makes it attractive to attend,” Devlin says.

Dr. Jon Mohrer, the internist from Forest Hills, Queens, is one busy doctor Celexa reps called on. “There is a constant barrage of drug reps in my life here, maybe five or six a day,” he says. “My policy is not to see anybody.” He says he doesn’t accept their gifts or literature and relies on journals and the nonprofit Medical Letter to check out new drugs. But it is hard to say no completely. For one thing, he sometimes accepts the free samples to save his patients money. “Sometimes the drug reps will come up and say, ‘Oh, thank you so much for prescribing my drug,’ ” he says. “It’s really annoying.”

Mohrer’s staff, however, is of a different opinion. The reps cultivate the office staff in order to get closer to the doctor, and once again, the drug rep’s principal weapon is a free lunch. “About once a month, I will let them come in and bring deli or pizza or something for the staff,” Mohrer says. “They love it.”

“What really annoyed me,” says internist Robert Goodman, “was physicians’ willingness to be bribed.”

Mohrer says he even feels a little bit sorry for the drug reps, who sometimes seem like glorified delivery people, and he has occasionally accepted their invitations. “I could go to dinner every night with a different drug rep if I wanted to,” he says. He and his wife recently attended a dinner cruise around Manhattan that featured an endocrinology lecture, and once they saw the play Rent with drug reps from Bristol Myers Squibb and their husbands. Until recently, Mohrer occasionally patronized “clinical sidebars,” too, stopping by Pasta Lovers or a popular kosher Chinese place near his home to pick up dinner for his family. “My kids like the Chinese food,” Mohrer says. “But I’m getting increasingly uncomfortable with it – I told my kids we’re not going to do it anymore, and they understand.”

Some doctors appreciate the reps, but they won’t say so openly. “The reps provide good information, and they are functioning in a system where that is how you sell medicine,” says a Connecticut psychiatrist who recently took in a Crosby, Stills, Nash & Young concert with his Zoloft rep.

One Manhattan psychiatrist who also asked not to be named says she has “learned a ton from drug reps and from their educational programs.” Sure, she says, they have taken her to fancy restaurants – Daniel, Lespinasse, Windows on the World – for talks or dinners with other psychiatrists to compare notes. “They have very respected speakers. You listen, and you either buy their case or you don’t,” she says. Her husband, another doctor, recently turned down an invitation to Acquavit because he felt it was a conflict of interest. “We missed a good meal,” she says. “It was a conflict for him, but it wouldn’t have been a conflict for me!”

Sometimes, drug reps provide valuable insights, she says. “My Pfizer rep is terrific and comes with a loose-leaf binder full of clippings from lots of reputable journals. She has done the research for me.” The psychiatrist says she doesn’t think marketing efforts make an undue difference. “Doctors just aren’t that corruptible,” she says.

She rarely prescribes Celexa. “I don’t like it,” she says. “In my experience, Celexa causes a lot more weight gain than some of the others, and jitters. I’ve had the same results three times in a row.” Her Celexa rep recently supplied a study purporting to show less weight gain than another drug, but she wasn’t convinced.

She and her husband recently spent a drug-company-sponsored educational weekend at a resort near Lake George in the Adirondacks. Most of their time was very agreeable – good food, walks in the woods, canoeing – and only a few hours were devoted to medicine.

Those few hours, however, nearly drove her husband into a rage. The experts on hand were addressing the virtues of calcium-channel blockers, a product for treating high blood pressure. He knew research shows that calcium-channel blockers are both more expensive and less effective than other treatments. As it happens, calcium-channel blockers are also the second most heavily marketed class of drug in the U.S., after antidepressants. “Of course marketing has an influence on prescribing!” the doctor says. “Why else would these calcium-channel blockers be so widely used?”

Inside the doctor’s office, the Celexa reps’ game is a kind of small-scale one-upmanship with the other antidepressants. For one thing, the reps emphasize that its side-effect profile is “cleaner” than Prozac’s – some tests suggest that Prozac made patients jittery, while Celexa didn’t. And the reps can make a strong case that Celexa is less likely to interact with other drugs. Likewise, it leaves a patient’s system more quickly than its rivals, which makes it easier to take a patient off the drug. Forest also elected to fix the drug’s price about ten percent lower than its rivals – a big selling point with insurers. Like other drug companies, Forest also constantly churns out new findings about its drug, to help the reps get back in the door. “Some physicians need to see fresh new information every time you come in there,” says Devlin.

Questions about Celexa’s potential for sexual side effects come up a lot, Backer says. “Now, we have some data to suggest that Celexa’s sexual side effects may be a little bit less than the others’, but that is not something that we are making our main selling point; we don’t want to overpromise,” she says. “We tell them some physicians say that Celexa is somewhat less likely to lead to sexual dysfunction, but it is hard to judge, and it is different with every patient.”

The idea that Celexa may be less likely to cause sexual dysfunction, however, has come across loud and clear. As soon as she heard the name Celexa, one New York psychotherapist’s first response was “Oh, yes, the one with fewer sexual side effects.” Amy Brodkey, a Philadelphia psychiatrist, says she doesn’t see drug reps but that her colleagues have picked up the same idea from their Celexa reps. “The current evidence suggests that it doesn’t cause weight gain or sexual dysfunction to the same extent,” says Dr. Steven Erle, an Upper East Side psychiatrist who not long ago enjoyed dinner at the restaurant Daniel with a Forest drug rep. “It seems likely that when we know more, the rate of sexual dysfunction won’t be nearly as high as with Prozac or Paxil.”

Forest’s strongest evidence for Celexa’s advantages on the sexual front were presented at the annual meeting of the American College of Neuro-Psychopharmacology in December. Dr. Marcel Waldinger, of the Hague, reported the first head-to-head comparison of the sexual effects of Celexa and another antidepressant, in this case Paxil. Thirty men who suffer from premature ejaculation – ejaculating an average of about 22 seconds after entering their partners – agreed to participate in a blind test. While having sex, their partners used stopwatches to time the men’s orgasms. Paxil delayed ejaculation until after about 170 seconds on average. But the men on Celexa still lasted only about 44 seconds, a lag the authors call “clinically irrelevant.” The results, Waldinger said in a Forest press release, “should be useful to clinicians, both when treating men who complain of premature ejaculation, as well as when trying to avoid unwanted sexual side effects in patients with depression.”

Failing to inhibit premature ejaculation, however, says little about Celexa’s potential to inhibit orgasm in other people. “That just doesn’t follow,” says Dr. William Appleton, a professor of psychiatry at Harvard and author of Prozac and the New Antidepressants. “I haven’t found that Celexa has fewer sexual side effects, but in any event, premature ejaculation is not the issue.”

Robert Goodman, an internist who works at Columbia-Presbyterian, tried for years to chase the drug reps out of his clinic. “What really annoyed me was physicians’ willingness to be bribed,” Goodman explained to me over a plate of rice and beans at a Dominican restaurant near the hospital. “Physicians, as a group, are pretty well off, but at professional conferences, they will wait in line a half an hour for a can of tennis balls or a free clock from a drug company. Then they’ll send their kids back up to get another!”

Finally, he decided to retaliate. He ordered pens, T-shirts, and coffee mugs of his own. He labeled them NO FREE LUNCH: JUST SAY NO TO DRUG REPS. Then he set up, an online compendium of facts and research about the influence of drug companies on medicine.

Goodman intended the site for health-care providers, but it makes disconcerting reading for patients. In one Harvard Medical School study, 85 doctors answered questions about two heavily marketed drugs, one for senile dementia and one for pain. Almost all the doctors said they relied only on academic research, but 71 percent repeated inaccurate information presented only in ads for the dementia drug. Nearly half the doctors fell into the same trap with the pain reliever.

Another surprising figure: The $10 billion the industry spends on marketing to doctors is more than the federal government pays for medical training. “It is a colossal waste!” Goodman says. “But the most comical thing is doctors’ attitudes. You will never hear a physician say, ‘This is influencing me.’ They are just so arrogant and naïve,” Goodman says.

Dr. Ruden, the busy physician on the Upper East Side, says he has been happy with Celexa’s results. And he insists that marketing has “no impact” on his practice. “No one in their right mind would admit that it could have an impact on their prescribing. You must really avoid the concept of being bought off by a dinner,” Ruden says. “I mean, I can afford to go to any place I want.”

When one drug rep recently invited him to a fancy dinner, he told her, “Here is what you can do. Buy me a Mercedes and put the name of your drug on the side. I will drive it around for you.” A week later, she brought him a small present. When Ruden tore off the wrapping paper, he found a Hot Wheels toy Mercedes with the name of the drug on the side. “Size matters,” he told her. They both had a big laugh.

Inside the Happiness Business