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Dr. Drug Rep
Via NY Transfer News Collective * All the News that Doesn't Fit
The New York Times Magazine - Nov 25, 2007
Great illustration by Leo Jung at the URL above:
Dr. Drug Rep
By DANIEL CARLAT
I. Faculty Development
On a blustery fall New England day in 2001, a friendly representative
from Wyeth Pharmaceuticals came into my office in Newburyport, Mass.,
and made me an offer I found hard to refuse. He asked me if Id like to
give talks to other doctors about using Effexor XR for treating
depression. He told me that I would go around to doctors offices
during lunchtime and talk about some of the features of Effexor. It
would be pretty easy. Wyeth would provide a set of slides and even pay
for me to attend a speakers training session, and he quickly floated
some numbers. I would be paid $500 for one-hour Lunch and Learn talks
at local doctors offices, or $750 if I had to drive an hour. I would
be flown to New York for a faculty-development program, where I would
be pampered in a Midtown hotel for two nights and would be paid an
I thought about his proposition. I had a busy private practice in
psychiatry, specializing in psychopharmacology. I was quite familiar
with Effexor, since I had read recent studies showing that it might be
slightly more effective than S.S.R.I.s, the most commonly prescribed
antidepressants: the Prozacs, Paxils and Zolofts of the world. S.S.R.I.
stands for selective serotonin reuptake inhibitor, referring to the
fact that these drugs increase levels of the neurotransmitter
serotonin, a chemical in the brain involved in regulating moods.
Effexor, on the other hand, was being marketed as a dual reuptake
inhibitor, meaning that it increases both serotonin and norepinephrine,
another neurotransmitter. The theory promoted by Wyeth was that two
neurotransmitters are better than one, and that Effexor was more
powerful and effective than S.S.R.I.s.
I had already prescribed Effexor to several patients, and it seemed to
work as well as the S.S.R.I.s. If I gave talks to primary-care doctors
about Effexor, I reasoned, I would be doing nothing unethical. It was a
perfectly effective treatment option, with some data to suggest
advantages over its competitors. The Wyeth rep was simply suggesting
that I discuss some of the data with other doctors. Sure, Wyeth would
benefit, but so would other doctors, who would become more educated
about a good medication.
A few weeks later, my wife and I walked through the luxurious lobby of
the Millennium Hotel in Midtown Manhattan. At the reception desk, when
I gave my name, the attendant keyed it into the computer and said, with
a dazzling smile: Hello, Dr. Carlat, I see that you are with the Wyeth
conference. Here are your materials.
She handed me a folder containing the schedule of talks, an invitation
to various dinners and receptions and two tickets to a Broadway
musical. Enjoy your stay, doctor. I had no doubt that I would, though
I felt a gnawing at the edge of my conscience. This seemed like a lot
of money to lavish on me just so that I could provide some education to
primary-care doctors in a small town north of Boston.
The next morning, the conference began. There were a hundred or so
other psychiatrists from different parts of the U.S. I recognized a
couple of the attendees, including an acquaintance I hadnt seen in a
while. Id heard that he moved to another state and was making a bundle
of money, but nobody seemed to know exactly how.
I joined him at his table and asked him what he had been up to. He said
he had a busy private practice and had given a lot of talks for
Warner-Lambert, a company that had since been acquired by Pfizer. His
talks were on Neurontin, a drug that was approved for epilepsy but that
my friend had found helpful for bipolar disorder in his practice. (In
2004, Warner-Lambert pleaded guilty to illegally marketing Neurontin
for unapproved uses. It is illegal for companies to pay doctors to
promote so-called off-label uses.)
I knew about Neurontin and had prescribed it occasionally for bipolar
disorder in my practice, though I had never found it very helpful. A
recent study found that it worked no better than a placebo for this
condition. I asked him if he really thought Neurontin worked for
bipolar, and he said that he felt it was great for some patients and
that he used it all the time. Given my clinical experiences with the
drug, I wondered whether his positive opinion had been influenced by
the money he was paid to give talks.
But I put those questions aside as we gulped down our coffees and took
seats in a large lecture room. On the agenda were talks from some of
the most esteemed academics in the field, authors of hundreds of
articles in the major psychiatric journals. They included Michael
Thase, of the University of Pittsburgh and the researcher who
single-handedly put Effexor on the map with a meta-analysis, and Norman
Sussman, a professor of psychiatry at New York University, who was
master of ceremonies.
Thase strode to the lectern first in order to describe his
groundbreaking work synthesizing data from more than 2,000 patients who
had been enrolled in studies comparing Effexor with S.S.R.I.s. At this
time, with his Effexor study a topic of conversation in the
mental-health world, Thase was one of the most well known and well
respected psychiatrists in the United States. He cut a captivating
figure onstage: tall and slim, dynamic, incredibly articulate and a
master of the research craft.
He began by reviewing the results of the meta-analysis that had the
psychiatric world abuzz. After carefully pooling and processing data
from eight separate clinical trials, Thase published a truly
significant finding: Effexor caused a 45 percent remission rate in
patients in contrast to the S.S.R.I. rate of 35 percent and the placebo
rate of 25 percent. It was the first time one antidepressant was shown
to be more effective than any other. Previously, psychiatrists chose
antidepressants based on a combination of guesswork, gut feeling and
tailoring a drugs side effects to a patients symptom profile. If
Effexor was truly more effective than S.S.R.I.s, it would amount to a
revolution in psychiatric practice and a potential windfall for Wyeth.
One impressive aspect of Thases presentation was that he was not
content to rest on his laurels; rather he raised a series of potential
criticisms of his results and then rebutted them convincingly. For
example, skeptics had pointed out that Thase was a paid consultant to
Wyeth and that both of his co-authors were employees of the company.
Thase responded that he had requested and had received all of the
companys data and had not cherry-picked from those studies most
favorable for Effexor. This was a significant point, because companies
sometimes withhold negative data from publication in medical journals.
For example, in 2004, GlaxoSmithKline was sued by Eliot Spitzer, who
was then the New York attorney general, for suppressing data hinting
that Paxil causes suicidal thoughts in children. The company settled
the case and agreed to make clinical-trial results public.
Another objection was that while the study was billed as comparing
Effexor with S.S.R.I.s in general, in fact most of the data compared
Effexor with one specific S.S.R.I.: Prozac. Perhaps Effexor was,
indeed, more effective than Prozac; this did not necessarily mean that
it was more effective than the other S.S.R.I.s in common use. But
Thase announced that since the original study, he had analyzed data on
Paxil and other meds and also found differences in remission rates.
For his study, Thase chose what was at that time an unusual measure of
antidepressant improvement: remission, rather than the more standard
measure, response. In clinical antidepressant trials, a response is
defined as a 50 percent improvement in depressive symptoms, as measured
by the Hamilton depression scale. Thus, if a patient enters a study
scoring a 24 on the Hamilton (which would be a moderate degree of
depression), he or she would have responded if the final score, after
treatment, was 12 or less.
Remission, on the other hand, is defined as complete recovery. While
you might think that a patient would have to score a 0 on the Hamilton
to be in remission, in fact very few people score that low, no matter
how deliriously happy they are. Instead, researchers come up with
various cutoff scores for remission. Thase chose a cutoff score of 7 or
In his study, he emphasized the remission rates and not the response
rates. As I listened to his presentation, I wondered why. Was it
because he felt that remission was the only really meaningful outcome
by which to compare drugs? Or was it because using remission made
Effexor look more impressive than response did? Thase indirectly
addressed this issue in his paper by pointing out that even when
remission was defined in different ways, with different cutoff points,
Effexor beat the S.S.R.I.s every time. That struck me as a pretty
convincing endorsement of Wyeths antidepressant.
The next speaker, Norm Sussman, took the baton from Thase and explored
the concept of remission in more detail. Sussmans job was to
systematically go through the officially sanctioned slide deck "
slides provided to us by Wyeth, which we were expected to use during
our own presentations.
If Thase was the riveting academic, Sussman was the engaging populist,
translating some of the drier research concepts into terms that our
primary-care-physician audiences would understand. Sussman exhorted us
not to be satisfied with response and encouraged us to set the bar
higher. Is the patient doing everything they were doing before they
got depressed? he asked. Are they doing it even better? Thats
remission. To further persuade us, he highlighted a slide showing that
patients who made it all the way to remission are less likely to
relapse to another depressive episode than patients who merely
responded. And for all its methodological limitations, it was a slide
that I would become well acquainted with, as I would use it over and
over again in my own talks.
When it came to side effects, Effexors greatest liability was that it
could cause hypertension, a side effect not shared by S.S.R.I.s.
Sussman showed us some data from the clinical trials, indicating that
at lower doses, about 3 percent of patients taking Effexor had
hypertension as compared with about 2 percent of patients assigned to a
placebo. There was only a 1 percent difference between Effexor and
placebo, he commented, and pointed out that treating high blood
pressure might be a small price to pay for relief from depression.
It was an accurate reading of the data, and I remember finding it a
convincing defense of Effexors safety. As I look back at my notes now,
however, I notice that another way of describing the same numbers would
have been to say that Effexor leads to a 50 percent greater rate of
hypertension than a placebo. Framed this way, Effexor looks more
And so it went for the rest of the afternoon.
Was I swallowing the message whole? Certainly not. I knew that this was
hardly impartial medical education, and that we were being fed a
marketing line. But when you are treated like the anointed, wined and
dined in Manhattan and placed among the leaders of the field, you
inevitably put some of your critical faculties on hold. I was truly
impressed with Effexors remission numbers, and like any physician, I
was hopeful that something new and different had been introduced to my
quiver of therapeutic options.
At the end of the last lecture, we were all handed envelopes as we left
the conference room. Inside were checks for $750. It was time to enjoy
ourselves in the city.
II. The Art and Science of Detailing
Pharmaceutical detailing is the term used to describe those sales
visits in which drug reps go to doctors offices to describe the
benefits of a specific drug. Once I returned to my Newburyport office
from New York, a couple of voice-mail messages from local Wyeth reps
were already waiting for me, inviting me to give some presentations at
local doctors offices. I was about to begin my speaking " and
detailing " career in earnest.
How many doctors speak for drug companies? We dont know for sure, but
one recent study indicates that at least 25 percent of all doctors in
the United States receive drug money for lecturing to physicians or for
helping to market drugs in other ways. This meant that I was about to
join some 200,000 American physicians who are being paid by companies
to promote their drugs. I felt quite flattered to have been recruited,
and I assumed that the rep had picked me because of some special
personal or professional quality.
The first talk I gave brought me back to earth rather quickly. I
distinctly remember the awkwardness of walking into my first waiting
room. The receptionist slid the glass partition open and asked if I had
Actually, Im here to meet with the doctor.
Oh, O.K. And is that a scheduled appointment?
Im here to give a talk.
A light went on. Oh, are you part of the drug lunch?
Regardless of how I preferred to think of myself (an educator, a
psychiatrist, a consultant), I was now classified as one facet of a
lunch helping to pitch a drug, a convincing sidekick to help the sales
rep. Eventually, with an internal wince, I began to introduce myself as
Dr. Carlat, here for the Wyeth lunch.
The drug rep who arranged the lunch was always there, usually an
attractive, vivacious woman with platters of gourmet sandwiches in tow.
Hungry doctors and their staff of nurses and receptionists would filter
into the lunch room, grateful for free food.
Once there was a critical mass (and crucially, once the M.D.s
arrived), I was given the go-ahead by the Wyeth reps to start. I dove
into my talk, going through a handout that I created, based on the
official slide deck. I discussed the importance of remission, the
basics of the Thase study showing the advantage of Effexor, how to dose
the drug, the side effects, and I added a quick review of the other
While I still had some doubts, I continued to be impressed by the 10
percent advantage in remission rates that Effexor held over S.S.R.I.s;
that advantage seemed significant enough to overcome Effexors more
prominent side effects. Yes, I was highlighting Effexors selling
points and playing down its disadvantages, and I knew it. But was my
salesmanship going to bring harm to anybody? It seemed unlikely. The
worst case was that Effexor was no more effective than anything else;
it certainly was no less effective.
During my first few talks, I worried a lot about my performance. Was I
too boring? Did the doctors see me as sleazy? Did the Wyeth reps find
me sufficiently persuasive? But the day after my talks, I would get a
call or an e-mail message from the rep saying that I did a great job,
that the doctor was impressed and that they wanted to use me more.
Indeed, I started receiving more and more invitations from other reps,
and I soon had talks scheduled every week. I learned later that Wyeth
and other companies have speaker-evaluation systems. After my talks,
the reps would fill out a questionnaire rating my performance, which
quickly became available to other Wyeth reps throughout the area.
As the reps became comfortable with me, they began to see me more as a
sales colleague. I received faxes before talks preparing me for
particular doctors. One note informed me that the physician wed be
visiting that day was a decile 6 doctor and is not prescribing any
Effexor XR, so please tailor accordingly. There is also one more doc in
the practice that we are not familiar with. The term decile 6 is
drug-rep jargon for a doctor who prescribes a lot of medications. The
higher the decile (in a range from 1 to 10), the higher the
prescription volume, and the more potentially lucrative that doctor
could be for the company.
A note from another rep reminded me of a scene from Mission:
Impossible. Dr. Carlat: Our main target, Dr. , is an internist. He
spreads his usage among three antidepressants, Celexa, Zoloft and
Paxil, at about 25-30 percent each. He is currently using about 6
percent Effexor XR. Our access is very challenging with lunches six
months out. This doctors schedule of lunches was filled with reps
from other companies; it would be vital to make our sales visit count.+
Nave as I was, I found myself astonished at the level of detail that
drug companies were able to acquire about doctors prescribing habits.
I asked my reps about it; they told me that they received printouts
tracking local doctors prescriptions every week. The process is called
prescription data-mining, in which specialized pharmacy-information
companies (like IMS Health and Verispan) buy prescription data from
local pharmacies, repackage it, then sell it to pharmaceutical
companies. This information is then passed on to the drug reps, who use
it to tailor their drug-detailing strategies. This may include deciding
which physicians to aim for, as my Wyeth reps did, but it can help
sales in other ways. For example, Shahram Ahari, a former drug rep for
Eli Lilly (the maker of Prozac) who is now a researcher at the
University of California at San Franciscos School of Pharmacy, said in
an article in The Washington Post that as a drug rep he would use this
data to find out which doctors were prescribing Prozacs competitors,
like Effexor. Then he would play up specific features of Prozac that
contrasted favorably with the other drug, like the ease with which
patients can get off Prozac, as compared with the hard time they can
have withdrawing from Effexor.
The American Medical Association is also a key player in prescription
data-mining. Pharmacies typically will not release doctors names to
the data-mining companies, but they will release their Drug Enforcement
Agency numbers. The A.M.A. licenses its file of U.S. physicians,
allowing the data-mining companies to match up D.E.A. numbers to
specific physicians. The A.M.A. makes millions in information-leasing
Once drug companies have identified the doctors, they must woo them. In
the April 2007 issue of the journal PLoS Medicine, Dr. Adriane
Fugh-Berman of Georgetown teamed up with Ahari (the former drug rep) to
describe the myriad techniques drug reps use to establish relationships
with physicians, including inviting them to a speakers meeting. These
can serve to cement a positive a relationship between the rep and the
doctor. This relationship is crucial, they say, since drug reps
increase drug sales by influencing physicians, and they do so with
finely titrated doses of friendship.
III. Uncomfortable Moments
I gave many talks over the ensuing several months, and I gradually
became more comfortable with the process. Each setting was somewhat
different. Sometimes I spoke to a crowded conference room with several
physicians, nurses and other clinical staff. Other times, I sat at a
small lunch table with only one other physician (plus the rep), having
what amounted to a conversation about treating depression. My basic
Effexor spiel was similar in the various settings, with the focus on
remission and the Thase data.
Meanwhile, I was keeping up with new developments in the research
literature related to Effexor, and not all of the news was positive.
For example, as more data came out comparing Effexor with S.S.R.I.s
other than Prozac, the Effexor remission advantage became slimmer "
more like 5 percent instead of the originally reported 10 percent.
Statistically, this 5 percent advantage meant that only one out of 20
patients would potentially do better on Effexor than S.S.R.I.s " much
less compelling than the earlier proportion of one out of 10.
I also became aware of other critiques of the original Thase
meta-analysis. For example, some patients enrolled in the original
Effexor studies took S.S.R.I.s in the past and presumably had not
responded well. This meant that the study population may have been
enriched with patients who were treatment-resistant to S.S.R.I.s,
giving Effexor an inherent advantage.
I didnt mention any of this in my talks, partly because none of it had
been included in official company slides, and partly because I was
concerned that the reps wouldnt invite me to give talks if I divulged
any negative information. But I was beginning to struggle with the
ethics of my silence.
One of my most uncomfortable moments came when I gave a presentation to
a large group of psychiatrists. I was in the midst of wrapping up my
talk with some information about Effexor and blood pressure. Referring
to a large study paid for by Wyeth, I reported that patients are liable
to develop hypertension only if they are taking Effexor at doses higher
than 300 milligrams per day.
Really? one psychiatrist in the room said. Ive seen hypertension at
lower doses in my patients.
I suppose it can happen, but its rare at doses that are commonly used
He looked at me, frowned and shook his head. That hasnt been my
I reached into my folder where I kept some of the key Effexor studies
in case such questions arose.
According to this study of 3,744 patients, the rate of high blood
pressure was 2.2 percent in the placebo group, and 2.9 percent in the
group of patients who had taken daily doses of Effexor no larger than
300 milligrams. Patients taking more than 300 milligrams had a 9
percent risk of hypertension. As I went through the numbers with the
doctor, however, I felt unsettled. I started talking faster, a sure
sign of nervousness for me.
Driving home, I went back over the talk in my mind. I knew I had not
lied " I had reported the data exactly as they were reported in the
paper. But still, I had spun the results of the study in the most
positive way possible, and I had not talked about the limitations of
the data. I had not, for example, mentioned that if you focused
specifically on patients taking between 200 and 300 milligrams per day,
a commonly prescribed dosage range, you found a 3.7 percent incidence
of hypertension. While this was not a statistically significant higher
rate than the placebo, it still hinted that such moderate doses could,
indeed, cause hypertension. Nor had I mentioned the fact that since the
data were derived from placebo-controlled clinical trials, the patients
were probably not representative of the patients seen in most real
practices. Patients who are very old or who have significant medical
problems are excluded from such studies. But real-world patients may
well be at higher risk to develop hypertension on Effexor. +
I realized that in my canned talks, I was blithely minimizing the
hypertension risks, conveniently overlooking the fact that hypertension
is a dangerous condition and not one to be trifled with. Why, I began
to wonder, would anyone prescribe an antidepressant that could cause
hypertension when there were many other alternatives? And why wasnt I
asking this obvious question out loud during my talks?
I felt rattled. That psychiatrists frown stayed with me " a mixture of
skepticism and contempt. I wondered if he saw me for what I feared I
had become " a drug rep with an M.D. I began to think that the money
was affecting my critical judgement. I was willing to dance around the
truth in order to make the drug reps happy. Receiving $750 checks for
chatting with some doctors during a lunch break was such easy money
that it left me giddy. Like an addiction, it was very hard to give up.
There was another problem: one of Effexors side effects. Patients who
stopped the medication were calling their doctors and reporting
symptoms like severe dizziness and lightheadedness, bizarre
electric-shock sensations in their heads, insomnia, sadness and
tearfulness. Some patients thought they were having strokes or nervous
breakdowns and were showing up in emergency rooms. Gradually, however,
it became clear that these were withdrawal symptoms. These were
particularly common problems with Effexor because it has a short
half-life, a measure of the time it takes the body to metabolize half
of the total amount of a drug in the bloodstream. Paxil, another short
half-life antidepressant, caused similar problems.
At the Wyeth meeting in New York, these withdrawal effects were
mentioned in passing, though we were assured that Effexor withdrawal
symptoms were uncommon and could usually be avoided by tapering down
the dose very slowly. But in my practice, that strategy often did not
work, and patients were having a very hard time coming off Effexor in
order to start a trial of a different antidepressant.
I wrestled with how to handle this issue in my Effexor talks, since I
believed it was a significant disadvantage of the drug. Psychiatrists
frequently have to switch medications because of side effects or lack
of effectiveness, and anticipating this potential need to change
medications plays into our initial choice of a drug. Knowing that
Effexor was hard to give up made me think twice about prescribing it in
the first place.
During my talks, I found myself playing both sides of the issue, making
sure to mention that withdrawal symptoms could be severe but assuring
doctors that they could usually be avoided. Was I lying? Not really,
since there were no solid published data, and indeed some patients had
little problem coming off Effexor. But was I tweaking and pruning the
truth in order to stay positive about the product? Definitely. And how
did I rationalize this? I convinced myself that I had told most of
the truth and that the potential negative consequences of this small
truth gap were too trivial to worry about.
As the months went on, I developed more and more reservations about
recommending that Effexor be used as a first line drug before trying
the S.S.R.I.s. Not only were the newer comparative data less
impressive, but the studies were short-term, lasting only 6 to 12
weeks. It seemed entirely possible that if the clinical trials had been
longer " say, six months " S.S.R.I.s would have caught up with
Effexor. Effexor was turning out to be an antidepressant that might
have a very slight effectiveness advantage over S.S.R.I.s but that
caused high blood pressure and had prolonged withdrawal symptoms.
At my next Lunch and Learn, I mentioned toward the end of my
presentation that data in support of Effexor were mainly short-term,
and that there was a possibility that S.S.R.I.s were just as
effective. I felt reckless, but I left the office with a restored sense
Several days later, I was visited by the same district manager who
first offered me the speaking job. Pleasant as always, he said: My
reps told me that you werent as enthusiastic about our product at your
last talk. I told them that even Dr. Carlat cant hit a home run every
time. Have you been sick?
At that moment, I decided my career as an industry-sponsored speaker
was over. The managers message couldnt be clearer: I was being paid
to enthusiastically endorse their drug. Once I stopped doing that, I
was of little value to them, no matter how much medical education I
IV. Life After Drug Money
A year after starting my educational talks for drug companies (I had
also given two talks for Forest Pharmaceuticals, pushing the
antidepressant Lexapro), I quit. I had made about $30,000 in
supplemental income from these talks, a significant addition to the
$140,000 or so I made from my private practice. Now I publish a
medical-education newsletter for psychiatrists that is not financed by
the pharmaceutical industry and that tries to critically assess drug
research and marketing claims. I still see patients, and I still
prescribe Effexor. I dont prescribe it as frequently as I used to, but
I have seen many patients turn their lives around because they
responded to this drug and to nothing else. +
In 2002, the drug industrys trade group adopted voluntary guidelines
limiting some of the more lavish benefits to doctors. While the
guidelines still allow all-expenses-paid trips for physicians to attend
meetings at fancy hotels, they no longer pay for spouses to attend the
dinners or hand out tickets to musicals. In an e-mail message, a Wyeth
spokesman wrote that Wyeth employees must follow that code and our own
Wyeth policies, which, in some cases, exceed the trade groups code.
Looking back on the year I spent speaking for Wyeth, Ive asked myself
if my work as a company speaker led me to do bad things. Did I
contribute to faulty medical decision making? Did my advice lead
doctors to make inappropriate drug choices, and did their patients
Maybe. Im sure I persuaded many physicians to prescribe Effexor,
potentially contributing to blood-pressure problems and withdrawal
symptoms. On the other hand, its possible that some of those patients
might have gained more relief from their depression and anxiety than
they would have if they had been started on an S.S.R.I. Not likely, but
I still allow drug reps to visit my office and give me their pitches.
While these visits are short on useful medical information, they do
allow me to keep up with trends in drug marketing. Recently, a rep from
Bristol-Myers Squibb came into my office and invited me to a dinner
program on the antipsychotic Abilify.
I think it will be a great program, Dr. Carlat, he said. Would you
like to come? I glanced at the invitation. I recognized the name of
the speaker, a prominent and widely published psychiatrist flown in
from another state. The restaurant was one of the finest in town.
I was tempted. The wine, the great food, the proximity to a famous
researcher " why not rejoin that inner circle of the select for an
evening? But then I flashed to a memory of myself five years earlier,
standing at a lectern and clearing my throat at the beginning of a
drug-company presentation. I vividly remembered my sensations " the
careful monitoring of what I would say, the calculations of how frank I
No, I said, as I handed the rep back the invitation. I dont think I
can make it. But thanks anyway.
[Daniel Carlat is an assistant clinical professor of psychiatry at Tufts
University School of Medicine and the publisher of The Carlat
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