The transformation of a Jacksonville psychiatrist from a skeptic on Seroquel into a super-prescriber was marked by months of gentle pestering, generous $1,500 speaking engagements and giveaways of everything from a plastic brain to gourmet chocolates.

A neurologist in Tampa joked with Seroquel sales reps that she doled out so much of the powerful antipsychotic drug for migraines that they probably thought she was psychiatrist. She was rewarded with free trips to Scotland and Spain. "I want to go too ! =)" her Seroquel rep wrote.

A busy Panama City physician had no problem leaving patients to stew in the waiting room while he listened to a pitch about Seroquel from a persistent saleswoman.

"Dr had 3 pat (patients) waiting and did sit down w (with) me," the rep wrote after a series of snubs at the front desk. "You never know what you will get w/Dr B."

Every day, legions of drug reps troop into doctors' offices, then scoot back to their cars and enter notes about their encounters onto laptops or handheld devices. They include reminders about everything from medical questions to the doctor's new Nissan 350Z or his kid's Eagle Scout badge.

The notes are uploaded to a secure database at company headquarters and used by the drug rep, her partners and managers as the company refines its sales spiel.

Thanks to thousands of lawsuits pending against Seroquel, AstraZeneca's best-selling antipsychotic, hundreds of pages of call notes concerning several Florida doctors recently were made public. Though specific to Seroquel, the salespeople's notes reflect industry-wide practices. They give insights into what happens behind closed doors while patients cool their heels.

It's not a pretty picture, with sales reps laying on the swag and doctors complaining about late honoraria and angling to get on the AstraZeneca's "advisory board."

Company spokesman Tony Jewell said the drug maker's philosophy is that "any interaction with health care providers should be about providing information that helps them decide on the right medicines, for the right patients, at the right time."

But notes from pharma's emissaries reflect two different goals: Get the doctor to prescribe the drug. Then push him to boost the dosage.

A sales rep in Jacksonville was ecstatic when a nurse practitioner prescribed Seroquel at twice the dosage used by the psychiatrist in the same practice.

"Gave him goodies," the rep wrote. "Biggest user of Seroquel in the office!"

• • •

AstraZeneca's sales reps have worked wonders. Though approved only for schizophrenia and bipolar disorder, relatively rare mental illnesses, Seroquel has been one of the world's best sellers. Last year sales reached $4.5 billion.

But Seroquel's widespread use for everything from insomnia to anxiety has also triggered lawsuits alleging the drug caused weight gain, diabetes and other health problems. AstraZeneca, a U.K.-based company, denies the charges, noting that the FDA has repeatedly upheld the safety of Seroquel.

It also has denied that its salespeople illegally promoted unapproved, or off-label, uses of the drugs to doctors. Reps "are trained to ensure that every product promotion discussion with (a) health care provider conforms to the FDA-approved prescribing information," Jewell said.

Company lawyers vigorously opposed unsealing sales reps' notes, saying they contained confidential, proprietary information. But at a recent hearing in Orlando's federal court, AstraZeneca agreed to release call notes from before January 2004, when Seroquel received FDA approval for bipolar mania.

Heavily redacted, the notes comprise what the company's commercial brand leader, Alfred Paulson, described as sales reps' "continuous conversation" with a half-dozen Florida health care providers who prescribed Seroquel to plaintiffs in pending lawsuits.

Depicting sales pitches, on which millions of dollars of revenue hinge, as simple "conversations" is an apt description for what, in the end, comes down to the chemistry between two people. Shahram Ahari, a drug rep for competitor Eli Lilly & Co. in 1999 and 2000, now lectures physicians on how to avoid being manipulated by well-trained marketing reps.

"As much as doctors want to think the relationship with a sales person is about the transfer of knowledge, it's the affinity between two people that's the big money-maker for the drug company," said Ahari, who is part of Pharmedout.org, a physician-education group in Washington, D.C. "That's why drug companies hire former cheerleaders and athletes as drug reps instead of scientists. It's a question of how gregarious and engaging you can be."

While AstraZeneca declined to comment on its employees' compensation, industry data shows drug reps earn an average of nearly $100,000 a year, including bonuses based on sales.

They learn sales techniques more often associated with door-to-door soliciting than medical offices. Doc too busy to see you? Send in several sales people, daily if necessary, until you get a sit-down. Show up on rainy days when patients cancel. And even highly paid physicians find it hard to resist a free lunch.

In 1999, Seroquel reps tried to waylay Dr. Maria Carmen Wilson, the Tampa neurologist, four times before hitting gold.

"We were able to speak to her at lunch that we brought for the office," a rep wrote.

Wilson moved from free food to free trips to medical meetings in Spain and Scotland. By early 2002, a drug rep noted that Wilson was using a "ton of Seroquel" for patients with migraines.

Wilson, who says she was surprised to learn that drug reps recorded their interactions with her, denies that she was ever a big Seroquel prescriber. Despite her initial hopes, she says the drug did not turn out to be effective against chronic headaches.

"I still use it in low doses for people with intractable insomnia," said Wilson, an associate professor at the University of South Florida. "But I make sure patients are acutely aware of the potential for weight gain, especially if they have a predisposition to diabetes."

Wilson says the industry-funded jaunts to Europe did not unduly influence her.

"I went because I want to be up-to-date and learn," she said of the seminars, which she did not report, as required, to USF officials. "But frankly, I'd prefer they were in Orlando."

• • •

The call notes show that massaging doctors' egos consumed an inordinate amount of a drug rep's time.

Saleswomen in Miami quickly honed in on psychiatrist Dr. Heriberto Cabada's need for extra schmoozing. "Would not pay attention, all about him," wrote one frustrated sales rep in 2001. So the line worker pulled in a "customer solutions" specialist who offered to redo the doc's patient history forms with a personalized logo.

She agreed to Cabada's demands for multiple revisions, "one side only and ... marbled type paper." More attention was funneled his way through a "preceptorship," in which a sales rep shadows the doctor for the day and pays for the honor.

In a few months, Cabada went from prescribing what he called "chicken dosages" of Seroquel to higher doses. Soon after his conversion, however, Cabada closed his practice and moved to Spain, where he now lives. He did not respond to an e-mail seeking comment.

Drug reps are taught to use free samples as a strategic weapon: Parcel them out sparingly, even if there are box loads in the trunk.

"It makes the doctor even more grateful," said former Lilly rep Ahari. "And when he gives a freebie to the patient, the doctor feels like a hero."

Dribbling samples out in small caches, and requiring the doctor's signature each time, also gives the rep another chance at valuable face time.

"Samples are key to access," wrote a sales rep who was routinely brushed off by Dr. John Roy Billingsley in Panama City.

AstraZeneca said it has voluntarily banned many of its "reminder" giveaways to docs — free pens, pads and hand wash emblazoned with drug names. But the company declined to say how such changes have affected its spending on physicians.

Ahari said he doubts drug companies have pared back their marketing budgets. "The money going to influence physicians is exactly the same,'' he said.

"There's absolutely no enforcement of these voluntary guidelines. All the incentives are still in place to wine and dine doctors at Hooters if he needs to."

The reason: it works.

Case in point: Dr. Mohamed O. Saleh, a Jacksonville psychiatrist who was involved in early clinical studies of Seroquel. In 1998, he was telling AstraZeneca reps that their product wasn't effective and two years later he was still dodging salesmen.

By 2003, however, the rep was crowing that Saleh "really loves seroquel for elderly... said that he would — dose of 800 (mg) and even higher if necessary!"

Saleh and his nurse practitioner, Richard Daniel Malcolm, were wooed with everything from holiday treats ("Left pumpkin candy baskets ... put seroquel labels on them") to a video of Saleh for his use during a visit to Africa in 2002.

AstraZeneca also furnished Saleh with freebies for the trip. The payoff: the doctor told the drug rep he would put a picture on his Web site showing "African healthcare workers holding the Seroquel bags filled with (a text book) and pens/etc. Appreciated our support."

Saleh, who said in July that he is still receiving $10,000 to $15,000 a year as a speaker for Seroquel, seemed aware of the persuasive power of drug company payola. In October 2003, he told AstraZeneca reps that he was concerned about his nurse practitioner, who had taken a fishing trip with the Seroquel rep and was pushing for his own speaking gigs.

"Concerned about payments to Dan (Malcolm) and can be inducement for scripts b/c paying so much," wrote one of the two reps assigned to Saleh's office.

Malcolm joined Saleh's office in June 2001, four months after he was disciplined by the Florida Board of Medicine for pleading guilty to charges of domestic battery, driving with a suspended license and fraud in obtaining a medicinal drug.

Neither Saleh nor Malcolm returned calls or e-mails seeking comment.

• • •

When doctors complained that patients were ballooning up on Seroquel, sales reps often handed them a study by Chicago psychiatrist Dr. Michael J. Reinstein. Its startling message: "Use of S (Seroquel) to reduce weight and reduce risk," according to a salesman who visited Panama City's Billingsley.

Back at headquarters, however, company executives had serious questions about the validity of Reinstein's findings. "Our clinical colleagues have significant and numerous issues in the past with the quality of research that this group has produced," a note from Seroquel's brand manager said in 2001.

While sales reps were not allowed to explicitly promote Seroquel for anything other than schizophrenia prior to 2004, the notes reflect a not-so-subtle, broad-based push.

In early 2000, Billingsley's sales rep wrote, "S best in new Schizo's, kids, adolescents, bi-pols, blacks and asians."

Dr. Guido Nodal, Jr., a psychiatrist in Hialeah, at first was cautious about Seroquel, fearing potential links to cataracts. In late 2001, he told a male sales rep he would keep the drug in mind only for "smoking sciz pts."

Two months later, however, a female rep wrote that Nodal "LOVES SER. FOR ELDERLY." By year's end he had 15 nursing home patients on the drug. (Later the FDA made all anti­psychotics warn that use in elderly with dementia could cause death.)

"Claims that he is switching patients from Risperdal to Seroquel at the nursing homes," a sales rep wrote in 2003. "Writing as much as he can to all patients."

Notes show that in the interim, Nodal received a textbook, mug, penlights ("Using lots"), payment for a preceptorship and dinner at Ruth's Chris Steak House. He denies the giveaways influenced his prescribing.

"If drug companies stopped marketing, I think prescribing (patterns) would be more or less the same as they are now,'' said Nodal, who said he tried to become a Seroquel speaker but was not accepted. "It didn't affect me at all."

Nodal closed his private practice last year and now works for the state's Department of Corrections in Florida City. The agency does not allow drug reps to lobby its physicians.

Times researcher Carolyn Edds contributed to this report. Kris Hundley can be reached at hundley@sptimes.com or (727) 892-2996.

Patients deserve facts about drug

Columbia Daily Tribune

Guns don't kill people; psychiatry does

By CHARLEY REESE (Former Orlando Sentinel columnist Charley Reese writes for King Features Syndicate.)

Star Tribune

People with dementia getting drugged rather than helped - 
Reliance on antipsychotics, especially at nursing homes, is under fire.

By WARREN WOLFE

March 9, 2008

It's hard to believe when you meet the vibrant 94-year-old Meta Miller today. But then her daughter Carol Johnson begins describing just how bad it got as she struggled to manage her mom's dementia at home for seven weeks before Thanksgiving in 2006.

"She would roam the house all night with her cane, talking to imaginary people, knocking things down, yelling at me, accusing me of horrible things -- my own mom," Johnson recalled with tears. "And it just got worse when she went to the first nursing home. That's when she started screaming."

To cope, thousands of nursing homes nationwide are doing what a hospice program and then a nursing home did for Miller: using powerful antipsychotic drugs to quiet disruptive people with dementia -- at times a step that's easier and cheaper than taking staff time to fix the problem.

The practice is alarming Medicaid officials. Last year, they ordered state nursing home inspectors to crack down on it.

Of the state's 398 nursing homes, 38 percent were cited last year for using such medications inappropriately, up from 27 percent in 2006.

So dangerous are the drugs that the Food and Drug Administration requires some to carry a "black box warning" that they heighten risk of death for older patients, a warning that it might extend to all antipsychotic drugs. They also increase the risk of confusion and falling.

The drugs often are prescribed whether the resident is psychotic or not.

More here: http://rs6.net/tn.jsp?e=001cq_MU8QP-9cTRpmIKZV4h3wLLQFLlpoTJNyU-rUV3216USz_M3sJc0sOk_Us_Gy-GhUR36xEZTbFt_54b7_ueHKafAX8krjXsR3qlWsXte9qEVrBq2Bqew==

Associated Press

Drugs in Water Could Affect Human Cells

Troubled by drugs discovered in European waters, poisons expert and biologist Francesco Pomati set up an experiment: He exposed developing human kidney cells to a mixture of 13 drugs at levels mimicking those found in Italian rivers.

There were drugs to fight high cholesterol and blood pressure, seizures and depression, pain and infection, and cancer, all in tiny amounts.

The result: The pharmaceutical blend slowed cell growth by up to a third - suggesting that scant amounts may exert powerful effects, said Pomati, who works at the University of New South Wales in Sydney, Australia.

Taken alone, this was a modest study. But in fact Pomati's work is part of a body of emerging scientific studies that indicate that over time, humans could be harmed by ingesting drinking water contaminated with tiny amounts of pharmaceuticals.