Where Doctors Get Their Information

January 24, 2012

Doctors spend four years in medical school, still more years in residency, and some devote even more years to fellowship training.   All of this work is done under direct supervision, and throughout the process, trainees learn from their teachers, mentors, and supervisors.  But medicine changes very rapidly.  After all of this training—i.e., once the doctor is “out in the real world”—how does he or she keep up with the latest developments?

Medical journals are the most obvious place to start.  Many doctors subscribe to popular journals like the New England Journal of Medicine or JAMA, or they get journals as a perk of membership in their professional society (for example, the American Journal of Psychiatry for members of the APA).  But the price of journals—and professional society memberships—can accumulate quickly, as can the stacks of unread issues on doctors’ desks.

A second source is continuing medical education credit.  “CMEs” are educational units that doctors are required to obtain in order to keep their medical license.  Some CME sources are excellent, although most CMEs are absurdly easy to obtain (e.g., you watch an online video; answer a few multiple-choice questions about a brief article; or show up for the morning session of a day-long conference, sign your name, then head out the door for a round of golf), making their educational value questionable.  Also, lots of CMEs are funded by pharmaceutical or medical device manufacturers (see here), where bias can creep in.

Direct communication with drug companies—e.g., drug sales reps—can also be a source of information.  Some universities and health-care organizations have “cracked down” on this interaction, citing inappropriate sales techniques and undue influence on doctors.  While docs can still contact the medical departments (or “medical science liaisons”) of big drug companies, this source of info appears to be running dry.

So what’s left?  Medical textbooks?  They’re usually several years out of date, even at the time of publication.  Medical libraries?  Unless you’re affiliated with a teaching hospital, those libraries are off-limits.  “Throwaway” journals?  Every specialty has them—they arrive in the mail, usually unrequested, and contain several topical articles and lots of advertising; but these articles generally aren’t peer-reviewed, and the heavy advertising tends to bias their content.  Medical websites?  Same thing.  (WebMD, for instance, is heavily funded by industry—a point that has not escaped the attention of watchdog senator Charles Grassley.)

Thus, the doctor in the community (think of the psychiatrist in a small group practice in your hometown) is essentially left alone, in the cold, without any unbiased access to the latest research.  This dilemma has become starkly apparent to me in the last several months.  Since last summer, I have worked primarily in a community hospital.  Because it is not an academic institution, it does not provide its employees or trainees access to the primary literature (and yes, that includes psychiatry residents).  I, on the other hand, have been fortunate enough to have had a university affiliation for most of my years of practice, so I can access the literature.  If I need to look up the details of a recent study, or learn about new diagnostic procedures for a given disorder, or prepare for an upcoming talk, I can find just about anything I need.  But this is not the case for my colleagues.  Instead, they rely on textbooks, throwaway journals, or even Wikipedia.  (BTW, Wikipedia isn’t so bad, according to a recent study out of Australia.  But I digress…)

Obviously, if one uses “free” resources to obtain medical information, that info is likely to be as unbiased as the last “free” Cymbalta dinner he or she attended.  Many doctors don’t recognize this.

When it comes to journals, it gets potentially more interesting.  All of the top medical journals are available online.  And, like many online newspapers and magazines, articles are available for a fee.  But the fees are astronomical—typically $30 or $35 per article—which essentially prohibits any doc from buying more than one or two, let alone doing exhaustive research on a given subject.

Interestingly, some articles are freely available (“open access” is the industry term).  You can try this yourself:  go to pubmed.gov and search for a topic like “bipolar disorder” or “schizophrenia.”  You’ll get thousands of results.  Some results are accompanied by the “Free Article” tag.  You can guess which articles most docs will choose to read.

Why are some articles free while others aren’t?  What’s the catch?  Well, sometimes there is no catch.  For one, the National Institutes of Health (NIH) requires any research done with its funding to be freely available within six months of a paper’s publication.  This makes sense: NIH funds are our tax dollars, so it’s only fair that we get to see the data.  (But even this is coming under attack, since the publishers want to protect their content—and revenue stream.)

Interestingly, though, some journals also have a “pay-for-open-access” policy, in which an author can pay a higher publication fee to make his/her article freely available.  In other words, if I publish a (non-NIH-funded) study but want it to reach a wider audience than simply those ivory-tower types with access to fully-stocked libraries, I can just pay extra.  That’s right, some publishers give me the option to pay to attract readers like community docs, the lay public, journalists, and others (not to mention potential investors in a company with which I’m affiliated).  The policy for Elsevier, one of the world’s largest academic publishers, on such “sponsored articles” can be found here.

You can see where this might lead.  Call me cynical, but paying for more eyeballs sounds a lot like advertising.  Of course, these are peer-reviewed articles, so they do meet some standards of scientific integrity.  (Or do they?  A recent article suggests that “narrative reviews” often misrepresent or overstate claims of medication efficacy.  See also this summary of the article by Neuroskeptic.)

Anyway, the take-home message is, unfortunately, one that we’ve heard all too often.  Science is supposed to be pristine, objective, and unbiased, but it’s clearly not.  Even when you take out the obvious advertising, the drug-rep showmanship, and the pharma-funded CME, there are still ways for a product-specific message to make its way to a doctor’s eyes and ears.  And if our medical journals supposedly represent the last bastion of scientific integrity—the sacred repository of truth in a world of direct-to-consumer advertising, biased KOLs, and Big Pharma largesse—we should be particularly cautious when they fail to serve that purpose.

9 Comments | business, marketing, psychiatry | Tagged: , , , , , , | Permalink
Posted by stevebMD

Latuda-Palooza: Marketing or Education?

October 2, 2011

In my last blog post, I wrote about an invitation I received to a symposium on Sunovion Pharmaceuticals’ new antipsychotic Latuda.  I was concerned that my attendance might be reported as a “payment” from Sunovion under the requirements of the Physicians Payment Sunshine Act.  I found it a bit unfair that I might be seen as a recipient of “drug money” (and all the assumptions that go along with that) when, in fact, all I wanted to do was learn about a new pharmaceutical agent.

As it turns out, Sunovion confirmed that my participation would NOT be reported (they start reporting to the feds on 1/1/12), so I was free to experience a five-hour Latuda extravaganza yesterday in San Francisco.  I was prepared for a marketing bonanza of epic proportion—a la the Viagra launch scene in “Love And Other Drugs.”  And in some ways, I got what I expected:  two outstanding and engaging speakers (Dr Stephen Stahl of NEI and Dr Jonathan Meyer of UCSD); a charismatic “emcee” (Richard Davis of Arbor Scientia); an interactive “clicker” system which allowed participants to answer questions throughout the session and check our responses in real time; full lunch & breakfast, coffee and snacks; all in a posh downtown hotel.  (No pens or mugs, though.)

The educational program consisted of a plenary lecture by Dr Stahl, followed by workshops in which we broke up into “teams” and participated in three separate activities:  first, a set of computer games (modeled after “Pyramid” and “Wheel Of Fortune”) in which we competed to answer questions about Latuda and earn points for our team; second, a “scavenger hunt” in which we had 5 minutes to find answers from posters describing Latuda’s clinical trials (sample question: “In Study 4 (229), what proportion of subjects withdrew from the Latuda 40 mg/d treatment arm due to lack of efficacy?”); and finally, a series of case studies presented by Dr Meyer which used the interactive clicker system to assess our comfort level in prescribing Latuda for a series of sample patients.  My team came in second place.

I must admit, the format was an incredibly effective way for Sunovion to teach doctors about its newest drug.  It reinforced my existing knowledge—and introduced me to a few new facts—while it was also equally accessible to physicians who had never even heard about Latuda.

Moreover, the information was presented in an unbiased fashion.  Unbiased?, you may ask.  But wasn’t the entire presentation sponsored by Sunovion?  Yes, it was, but in my opinion the symposium achieved its stated goals:  it summarized the existing data on Latuda (although see here for some valid criticism of that data); presented it in a straightforward, effective (and, at times, fun) way; and allowed us doctors to make our own decisions.  (Stahl did hint that the 20-mg dose is being studied for bipolar depression, not an FDA-approved indication, but that’s also publicly available on the clinicaltrials.gov website.)  No one told us to prescribe Latuda; no one said it was better than any other existing antipsychotic; no one taught us how to get insurance companies to cover it; and—in case any “pharmascold” is still wondering—no one promised us any kickbacks for writing prescriptions.

(Note:  I did speak with Dr Stahl personally after his lecture.  I asked him about efforts to identify patient-specific factors that might predict a more favorable response to Latuda than to other antipsychotics.  He spoke about current research in genetic testing, biomarkers, and fMRI to identify responders, but he also admitted that it’s all guesswork at this point.  “I might be entirely wrong,” he admitted, about drug mechanisms and how they correlate to clinical response, and he even remarked “I don’t believe most of what’s in my book.”  A refreshing—and surprising—revelation.)

In all honesty, I’m no more likely to prescribe Latuda today than I was last week.  But I do feel more confident in my knowledge about it.  It is as if I had spent five hours yesterday studying the Latuda clinical trials and the published Prescribing Information, except that I did it in a far more engaging forum.  As I mentioned to a few people (including Mr Davis), if all drug companies were to hold events like this when they launch new agents, rather than letting doctors decipher glossy drug ads in journals or from their drug reps, doctors would be far better educated than they are now when new drugs hit the market.

But this is a very slippery slope.  In fact, I can’t help but wonder if we may be too far down that slope already.  For better or for worse, Steve Stahl’s books have become de facto “standard” psychiatry texts, replacing classics like Kaplan & Sadock, the Oxford Textbook, and the American Psychiatric Press books.  Stahl’s concepts are easy to grasp and provide the paradigm under which most psychiatry is practiced today (despite his own misgivings—see above).  However, his industry ties are vast, and his “education” company, Neuroscience Education Institute (NEI), has close connections with medical communications companies who are basically paid mouthpieces for the pharmaceutical industry.  Case in point: Arbor Scientia, which was hired by Sunovion to organize yesterday’s symposium—and similar ones in other cities—shares its headquarters with NEI in Carlsbad, CA, and Mr Davis sits on NEI’s Board.

We may have already reached a point in psychiatry where the majority of what we consider “education” might better be described as marketing.  But where do we draw the line between the two?  And even after we answer that question, we must ask, (when) is this a bad thing?  Yesterday’s Sunovion symposium may have been an infomercial, but I still felt there was a much greater emphasis on the “info-” part than the “-mercial.”  (And it’s unfortunate that I’d be reported as a recipient of pharmaceutical money if I had attended the conference after January 1, 2012, but that’s for another blog post.)  The question is, who’s out there to make sure it stays that way?

I’ve written before that I don’t know whom to trust anymore in this field.  Seemingly “objective” sources—like lectures from my teachers in med school and residency—can be heavily biased, while “advertising” (like yesterday’s symposium) can, at times, be fair and informative.  The end result is a very awkward situation in modern psychiatry that is easy to overlook, difficult to resolve, and, unfortunately, still ripe for abuse.

25 Comments | antipsychotics, business, marketing, psychopharmacology | Tagged: , , , , , , , | Permalink
Posted by stevebMD

“Dollars For Docs” – What It Really Means

September 25, 2011

A few weeks ago I received an invitation to an October 1 symposium on Latuda, a new antipsychotic from Sunovion (formerly known as Sepracor).  Latuda (lurasidone) was released about six months ago amidst much fanfare—and very aggressive marketing—as a new atypical antipsychotic with, among other advantages, pro-cognitive properties.

I have only prescribed Latuda to three patients, so I have only limited experience with it.  (In case you’re wondering:  one success, one failure, one equivocal.)  However, I have read several papers about Latuda, and I am interested in learning more about it.  The symposium’s plenary speaker is Stephen Stahl from the Neuroscience Education Institute.  Dr Stahl has received money from Sunovion (which is obvious from his publications and disclosures) but he is also a very knowledgeable neuroscientist.  I figured he would be able to describe the differences between Latuda and the other atypical antipsychotics currently on the market.  So I accepted the invitation.

However, upon further thought, I wondered whether my attendance might represent a “payment” from the Sunovion Corporation.  I was not offered any money from Sunovion to attend this event (in fact, you can see my invitation here: page1, page2).  Nevertheless, according to the Physician Payment Sunshine Act, which was passed as part of PPACA (i.e., “Obamacare”), all pharmaceutical companies and medical device manufacturers, as of 2013, are required to report payments to physicians, including direct compensation as well as “food, entertainment, research funding, education or conference funding,” and so forth.

Despite the mandatory 2013 reporting date, several companies have already started reporting.  Other major drug firms to self-report thus far include AstraZeneca, Eli Lilly, Merck, and Pfizer.  Their reports have been widely publicized at sites such as “Dollars For Docs,” which “allows the public to search for individual physicians to see whether they’ve been on pharma’s payroll.”  Several other sites encourage patients to use this site to ask “Does your doc get money from drug companies?”

A quick search of my own name reveals that I received $306 from Pfizer in the year 2010.  Wow!  I had no idea!  What exactly does this mean?  Am I a Pfizer slave?  Did my Pfizer rep walk up to me on 12/31/10, hand me a personal check for $306 and say, “Thank you, Dr. Balt, for prescribing Geodon and Pristiq this year—here’s $306 for your work, and we look forward to more in 2011”?

The answer is no.  I received no money from Pfizer (and, to be frank, I didn’t prescribe any Pristiq last year, because it’s essentially Effexor).  As it happens, during 2010 I worked part-time at a community mental health clinic.  The clinic permitted drug reps to come to the office, bring lunch, and distribute information about their products.  We had lunches 1-2 days out of the week, consisting of modest fare:  Panera sandwiches, trays of Chinese food, or barbecued ribs.  Most of the doctors didn’t have time to eat—or if we did, we scarfed it down in between patients—but we would often talk to the reps, ask questions about their drugs, and accept product literature (which virtually always went straight into the trash), reprints, and educational materials from them.

We were visited by most of the major drug companies in 2010.  (BTW, this continued into 2011, but we are no longer allowed—under our contract with the County mental health department—to accept free samples, and we no longer accept lunches.  Interestingly, my Pfizer rep told us that payments would be reported only as of 1/1/11 and NOT earlier; obviously that was untrue.)  All of the lunches were generally the same, and consisted of inexpensive, modest food, mainly consumed by the clinic staff—secretaries, administrators, assistants—since the doctors were actually working through the lunch hour.  I have since learned that the formula for calculating doctors’ payouts was to take the full cost of the lunch (including all staff members, remember), divide it by the number of doctors in the office, and report that sum.   That’s where you get my $306.00.

[In the interest of full disclosure, in my four years of practice post-residency, I have only been offered one “material” non-food gift: about three years ago, Janssen gave me a $100 voucher for a textbook; I used it to purchase Glen Gabbard’s psychodynamic psychotherapy text.]

Anyway, back to the Latuda symposium.  Knowing what I now know about drug companies, I wouldn’t be surprised if Sunovion reports a $1000+ payout to me if I attend this half-day symposium.  (Facility rental + A/V costs + Xeroxing/handouts + coffee service + refreshments, all divided by the # of docs in attendance.)  I frankly don’t want my future patients searching my name on Dollars For Docs and finding I received a huge “payment” from Sunovion in Q3 2011.  On the other hand, I would like to learn more about Latuda and whether/how it differs from other antipsychotics on the market (including generic first-generation agents).  If possible, I would also like to question Steve Stahl directly about some of what he’s written about this drug (including his Sunovion-funded articles).  What better forum to do this than in a public symposium??

[Note: please see ADDENDUM below.]  I have contacted two different Sunovion sales reps to ask whether my attendance will be “reported” as a payment, and if so, how much.  I have not received a response.  I also called the RSVP number for the symposium.  The registration is being managed by Arbor Scientia, a medical communications company contracted by Sunovion to manage these events.  I was directed to Heather of Arbor Scientia; I left her a message but have not yet received a return call.

So at this point, I am looking forward to attending an event to learn more about a new drug—and the opportunity to challenge the experts on the advantages (if any) of this drug over others—but in doing so, I might also be reported as having “received” a large payment from Sunovion, perhaps even larger than what Pfizer reported they paid me in 2010.

Patients should recognize that sometimes the only way for their doctors to learn about new drugs is to attend such events (assuming they can remain objective, which can be hard when the wine is freely flowing!).  Admittedly, there are doctors who accept much larger sums as speakers or “key opinion leaders,” but organizations like ProPublica should differentiate those doctors (with whom I, personally, have an ethical gripe) from those who are simply workaday folks like me who want to get as much information as they can, provide effective and cost-efficient care—and maybe inhale a free sandwich every once in a while.

ADDENDUM Sept. 26:  Today I received a phone call from Arbor Scientia (from a number that is actually registered as NEI’s main number—as it turns out, they are located in the same building) to assure me that Sunovion adheres to the Physician’s Sunshine Act provision: namely, that they’ll report “payments” to doctors only after January 1, 2012.  (See also here.)  Interestingly, my local Sunovion rep had told me 1/1/11.  (This is only somewhat reassuring: my Pfizer rep had told me they would start reporting as of 1/1/11, but clearly my “payments” from 2010 were reported.)

50 Comments | antipsychotics, community mental health, marketing, psychopharmacology | Tagged: , , , , | Permalink
Posted by stevebMD

How To Get Rich In Psychiatry

August 17, 2011

Doctors choose to be doctors for many reasons.  Sure, they “want to help people,” they “enjoy the science of medicine,” and they give several other predictable (and sometimes honest) explanations in their med school interviews.  But let’s be honest.  Historically, becoming a doctor has been a surefire way to ensure prestige, respect, and a very comfortable income.

Nowadays, in the era of shrinking insurance reimbursements and increasing overhead costs, this is no longer the case.  If personal riches are the goal, doctors must graze other pastures.  Fortunately, in psychiatry, several such options exist.  Let’s consider a few.

One way to make a lot of money is simply by seeing more patients.  If you earn a set amount per patient—and you’re not interested in the quality of your work—this might be for you.  Consider the following, recently posted by a community psychiatrist to an online mental health discussion group:

Our county mental health department pays my clinic $170 for an initial evaluation and $80 for a follow-up.  Of that, the doctor is paid $70 or $35, respectively, for each visit.  There is a wide range of patients/hour since different doctors have different financial requirements and philosophies of care.  The range is 3 patients/hour to 6 patients/hour.

This payment schedule incentivizes output.  A doctor who sees three patients an hour makes $105/hr and spends 20 minutes with each patient.  A doctor who sees 6 patients an hour spends 10 minutes with each patient and makes $210.  One “outlier” doctor in our clinic saw, on average, 7 patients an hour, spending roughly 8 minutes with each patient and earning $270/hr.  His clinical notes reflected his rapid pace…. [but] Despite his shoddy care of patients, he was tolerated at the clinic because he earned a lot of money for the organization.

If this isn’t quite your cup of tea, you can always consider working in a more “legit” capacity, like the Department of Corrections.  You may recall the Bloomberg report last month about the prison psychiatrist who raked in over $800,000 in one year—making him the highest-paid state employee in California.  As it turns out, that was a “data entry error.”  (Bloomberg issued a correction.)  Nevertheless, the cat was out of the bag: prison psychiatrists make big bucks (largely for prescribing Seroquel and benzos).  With seniority and “merit-based increases,” one prison shrink in California was able to earn over $600,000—and that’s for a shrink who was found to be “incompetent.”  Maybe they pay the competent ones even more?

Another option is to be a paid drug speaker.  I’m not referring to the small-time local doc who gives bland PowerPoint lectures to his colleagues over a catered lunch of even blander ham-and-cheese sandwiches.  No sir.  I’m talking about the psychiatrists hired to fly all around the country to give talks at the nicest five-star restaurants in the nation’s biggest drug markets cities.  The advantage here is that you don’t even have to be a great doc.  You just have to own a suit, follow a script, speak well, and enjoy good food and wine.

As most readers of this blog know, ProPublica recently published a list of the sums paid by pharmaceutical companies to doctors for these “educational programs.”  Some docs walked away with checks worth tens—or hundreds—of thousands of dollars.  And, not surprisingly, psychiatrists were the biggest offenders earners.  I guess there is gold in explaining the dopamine hypothesis or the mechanism of neurotransmitter reuptake inhibition to yet another doctor.

Which brings me to perhaps the most tried-and-true way to convert one’s medical education into cash:  become an entrepreneur.  Discovering a new drug or unraveling a new disease process might revolutionize medical care and improve the lives of millions.  And throughout the history of medicine, numerous physician-researchers have converted their groundbreaking discoveries (or luck) into handsome profits.

Unfortunately, in psychiatry, paradigm shifts of the same magnitude have been few and far between.  Instead, the road to riches has been paved by the following formula: (1) “Buy in” to the prevailing disease model (regardless of its biological validity); (2) Develop a drug that “fits” into the model; (3) Find some way to get the FDA to approve it; (4) Promote it ruthlessly; (5) Profit.

In my residency program, for example, several faculty members founded a biotech company whose sole product was a glucocorticoid receptor antagonist which, they believed, might treat psychotic depression (you know, with high stress hormones in depression, etc).  The drug didn’t work (rendering their stock options worth only millions instead of tens of millions).  But that didn’t stop them.  They simply searched for other ways to make their compound relevant.  As I write, they’re looking at it as a treatment for Cushing’s syndrome (a more logical—if far less profitable—indication).

The psychiatry blogger 1boringoldman has written a great deal about the legions of esteemed academic psychiatrists who have gotten caught up in the same sort of rush (no pun intended) to bring new drugs to market.  His posts are definitely worth a read.  Frankly, I see no problem with psychiatrists lending their expertise to a commercial enterprise in the hopes of capturing some of the windfall from a new blockbuster drug.  Everyone else in medicine does it, why not us?

The problem, as mentioned above, is that most of our recent psychiatric meds are not blockbusters.  Or, to be more accurate, they don’t represent major improvements in how we treat (or even understand) mental illness.  They’re largely copycat solutions to puzzles that may have very little to do with the actual pathology—not to mention psychology—of the conditions we treat.

To make matters worse, when huge investments in new drugs don’t pay off, investigators (including the psychiatrists expecting huge dividends) look for back-door ways to capture market share, rather than going back to the drawing board to refine their initial hypotheses.  Take, for instance, RCT Logic, a company whose board includes the ubiquitous Stephen Stahl and Maurizio Fava, two psychiatrists with extensive experience in clinical drug trials.  But the stated purpose of this company is not to develop novel treatments for mental illness; they have no labs, no clinics, no scanners, and no patients.  Instead, their mission is to develop clinical trial designs that “reduce the detrimental impact of the placebo response.”

Yes, that’s right: the new way to make money in psychiatry is not to find better ways to treat people, but to find ways to make relatively useless interventions look good.

It’s almost embarrassing that we’ve come to this point.  Nevertheless, as someone who has decidedly not profited (far from it!) from what I consider to be a dedicated, intelligent, and compassionate approach to my patients, I’m not surprised that docs who are “in it for the money” have exploited these alternate paths.  I just hope that patients and third-party payers wake up to the shenanigans played by my colleagues who are just looking for the easiest payoff.

But I’m not holding my breath.

Footnote:  For even more ways to get rich in psychiatry, see this post by The Last Psychiatrist.

20 Comments | business, community mental health, marketing, mental health, psychiatry, society | Tagged: , , , , , , | Permalink
Posted by stevebMD

Critical Thinking and Drug Advertising

August 14, 2011

One of the advantages of teaching medical students is that I can keep abreast of changes in medical education.  It’s far too easy for a doctor (even just a few years out of training) to become complacent and oblivious to changes in the modern medical curriculum.  So I was pleasantly surprised earlier this week when a fourth-year medical student told me that his recent licensing examination included a vignette which tested his ability to interpret data from a pharmaceutical company advertisement.  Given that most patients (and, indeed, most doctors) now get their information from such sources, it was nice to see that this is now part of a medical student’s education.

For those of you unfamiliar with the process, the US Medical Licensing Examination (USMLE) is a three-step examination that all medical students must take in order to obtain a medical license in the United States.  Most students take steps 1 and 2 during medical school, while step 3 is taken during residency.

Effective this month, the drug-ad questions will appear in the Step 2 examination.  Obviously, I don’t have access to the particular ad that my med student saw, but here’s a sample item taken from the USMLE website (click to enlarge):


It’s attractive and seems concise.  It’s certainly easier to read—some might even say more “fun”—than a dry, boring journal article or data table.  But is it informative?  What would a doctor need to know to confidently prescribe this new drug?  That’s the emphasis of this new type of test question.  Specifically, the two questions pertaining to this item ask the student (1) to identify which statement is most strongly supported by information in the ad, and (2) which type of research design would give the best data in support of using this drug.

It’s good to know that students are being encouraged to ask such questions of themselves (and, more importantly, one would hope, of the people presenting them with such information).  For comparison, here are two “real-world” examples of promotional advertising I have received for two recently launched psychiatric drugs:


Again, nice to look at.  But essentially devoid of information.  Okay, maybe that’s unfair:  Latuda was found to be effective in “two studies for each dose,” and the Oleptro ad claims that “an eight-week study showed that depression symptoms improved for many people taking Oleptro.”  But what does “effective” mean?  What does “improved” mean?  Where’s the data?  How do these drugs compare to medications we’ve been using for years?  Those are the questions that we need to ask, not only to save costs (new drugs are expensive) but also to prevent exposing our patients to adverse effects that only emerge after a period of time on a drug.

(To be fair, it is quite easy to obtain this information on the drug company’s web sites, or by asking the respective drug reps.  But first impressions count for a lot, and how many providers actually ask for the info?  Or can understand it once they do get it??)

The issue of drug advertising and its influence on doctors has received a good degree of attention lately.  An article in PLoS Medicine last year found that exposure to pharmaceutical company information was frequently (although not always) associated with more prescriptions, higher health care costs, or lower prescribing quality.  Similarly, a report last May in the Archives of Otolaryngology evaluated 50 drug ads in otolaryngology (ENT) journals and found that only 14 (28%) of those claims were based on “strong evidence.”  And the journal Emergency Medicine Australasia went one step further last February and banned all drug company advertising, claiming that “marketing of drugs by the pharmaceutical industry, whose prime aim is to bias readers towards prescribing a particular product, is fundamentally at odds with the mission of medical journals.”

The authors of the PLoS article even wrote the editors of the Lancet, one of the world’s top medical journals, to ask if they’d be willing to ban drug ads, too.  Unfortunately, banning drug advertising may not solve the problem either.  As discussed in an excellent article by Harriet Washington in this summer’s American Scholar, drug companies have great influence over the research that gets funded, carried out, and published, regardless of advertising.  Washington writes: “there exist many ways to subvert the clinical-trial process for marketing purposes, and the pharmaceutical industry seems to have found them all.”

As I’ve written before, I have no philosophical—or practical—opposition to pharmaceutical companies, commercial R&D, or drug advertising.  But I am opposed to the blind acceptance of messages that are the direct product of corporate marketing departments, Madison Avenue hucksters, and drug-company shills.  It’s nice to know that the doctors of tomorrow are being taught to ask the right questions, to become aware of bias, and to develop stronger critical thinking skills.  Hopefully this will help them to make better decisions for their patients, rather than serve as unwitting conduits for big pharma’s more wasteful wares.

5 Comments | business, marketing, medications | Tagged: , , , | Permalink
Posted by stevebMD

Big Brother in Your Medicine Cabinet

June 29, 2011

If there’s one thing I’ve learned from working as a doctor, it is that “what the doctor ordered” is not always what the patient gets.  Sure, I’ve encountered the usual obstacles—like pharmacy “benefit” (ha!) managers whose restrictive formularies don’t cover the medications ordered by their physicians—but I’ve also been amazed by the number of patients who don’t take medications as prescribed.  In psychiatry, the reasons are numerous:  patients may take their SSRI “only when I feel depressed,” they double their dose of a benzodiazepine “because I like the way it makes me feel,” they stop taking two or three of their six medications out of sheer confusion, or they take a medication for entirely different purposes than those for which it was originally prescribed.  (If I had a nickel for every patient who takes Seroquel “to help me sleep,” I’d be a very rich man.)

In the interest of full disclosure, this is not limited to my patients.  Even in my own life, I found it hard to take my antidepressant daily (it really wasn’t doing anything for me, and I was involved in other forms of treatment and lifestyle change that made a much bigger difference).  And after a tooth infection last summer, it was a real challenge to take my penicillin three times a day.  I should know better.  Didn’t I learn about this in med school??

This phenomenon used to be called “noncompliance,” a term which has been replaced by the more agreeable term, “nonadherence.”  It’s rampant.  It is estimated to cost the US health care system hundreds of billions of dollars annually.  But how serious is it to human health?  The medical community—with the full support of Big Pharma, mind you—wants you to believe that it is very serious indeed.  In fact, as the New York Times reported last week, we now have a way to calculate a “risk score” for patients who are likely to skip their medications.  Developed by the FICO company, the “Medication Adherence Score” can predict “which patients are at highest risk for skipping or incorrectly using” their medications.

FICO?  Where have you heard of them before?  Yes, that’s right, they’re the company who developed the credit score:  that three-digit number which determines whether you’re worthy of getting a credit card, a car loan, or a home mortgage.  And now they’re using their clout and influence actuarial skills to tell whether you’re likely to take your meds correctly.

To be sure, some medications are important to take regularly, such as antiretrovirals for HIV, anticoagulants, antiarrhythmics, etc, because of the risk of severe consequences after missed doses.  As a doctor, I entered this profession to improve lives—and oftentimes medications are the best way for my patients to thrive.  [Ugh, I just can’t use that word anymore… Kaiser Permanente has ruined it for me.]

But let’s consider psychiatry, shall we?  Is a patient going to suffer by skipping Prozac or Neurontin for a few days?  Or giving them up altogether to see an acupuncturist instead?  That’s debatable.

Anyway, FICO describes their score as a way to identify patients who would “benefit from follow-up phone calls, letters, and emails to encourage proper use of medication.”  But you can see where this is going, can’t you?  It’s not too much of a stretch to see the score being used to set insurance premiums and access (or lack thereof) to name-brand medications.  Hospitals and clinics might also use it to determine which patients to accept and which to avoid.

Independently (and coincidentally?), the National Consumers League inaugurated a program last month called “Script Your Future,” which asks patients to make “pledges” to do things in the future (like “walk my daughter down the aisle” or “always be there for my best friend”) that require—or so it is implied—adherence to their life-saving medications.  Not surprisingly, funds for the campaign come from a coalition including “health professional groups, chronic disease groups, health insurance plans, pharmaceutical companies, [and] business organizations.”  In other words: people who want you to take drugs.

The take-home message to consumers patients, of course, is that your doctors, drug companies, and insurers care deeply about you and truly believe that adherence to your medication regimen is the key to experiencing the joy of seeing your children graduate from college or retiring to that villa in the Bahamas.  Smile, take our drugs, and be happy.  (And don’t ask questions!)

If a patient doesn’t want to take a drug, that’s the patient’s choice—which, ultimately, must always be respected (even if ends up shortening that patient’s life).  At the same time, it’s the doctor’s responsibility to educate the patient, figure out the reasons for this “nonadherence,” identify the potential dangers, and help the patient find suitable alternatives.  Perhaps there’s a language barrier, a philosophical opposition to drugs, a lack of understanding of the risks and benefits, or an unspoken cultural resistance to Western allopathic medicine.  Each of these has its merits, and needs to be discussed with the patient.

Certainly, if there are no alternatives available, and a patient still insists on ignoring an appropriate and justifiable medical recommendation, we as a society have to address how to hold patients accountable, so as not to incur greater costs to society down the road (I’m reminded here of Anne Fadiman’s excellent book The Spirit Catches You And You Fall Down).  At the same time, though, we might compensate for those increased costs by not overprescribing, overtreating, overpathologizing, and then launching campaigns to make patients complicit in (and responsible for!) these decisions.

Giving patients a “score” to determine whether they’re going to take their meds is the antithesis of good medicine.  Good medicine requires discussion, interaction, understanding, and respect.  Penalizing patients for not following doctors’ orders creates an adversarial relationship that we can do without.

24 Comments | business, marketing, medications, psychopharmacology | Tagged: , , , , | Permalink
Posted by stevebMD

Psychopharm R&D Cutbacks: Crisis or Opportunity?

June 19, 2011

The scientific journal Nature ran an editorial this week with a rather ominous headline: “Psychopharmacology in Crisis.”  What exactly is this “crisis” they speak of?  Is it the fact that our current psychiatric drugs are only marginally effective for many patients?  Is it the fact that they can often cause side effects that some patients complain are worse than the original disease?  No, the “crisis” is that the future of psychopharmacology is in jeopardy, as pharmaceutical companies, university labs, and government funding agencies devote fewer resources to research and development in psychopharmacology.  Whether this represents a true crisis, however, is entirely in the eye of the beholder.

In 2010, the pharmaceutical powerhouses Glaxo SmithKline (GSK) and AstraZeneca closed down R&D units for a variety of CNS disorders, a story that received much attention.  They suspended their research programs because of the high cost of bringing psychiatric drugs to market, the potential for lawsuits related to adverse events, and the heavy regulatory burdens faced by drug companies in the US and Europe.  In response, organizations like the European College of Neuropsychopharmacology (ECNP) and the Institute of Medicine in the US have convened summits to determine how to address this problem.

The “problem,” of course, for pharmaceutical companies is the potential absence of a predictable revenue stream.  Over the last several years, big pharma has found it to be more profitable not to develop novel drugs, but new niches for existing agents—a decision driven by MBAs instead of MDs and PhDs.  As Steve Hyman, NIMH director, told Science magazine last June,  “It’s hardly a rich pipeline.  It suggests a sad dearth of ideas and … lots of attempts at patent extensions and new indications for old drugs.”

Indeed, when I look back at the drug approvals of the last three or four years, there really hasn’t been much to get excited about:  antidepressants (Lexapro, Pristiq, Cymbalta) that are similar in mechanism to other drugs we’ve been using for years; new antipsychotics (Saphris, Fanapt, Latuda) that are essentially me-too drugs which don’t dramatically improve upon older treatments; existing drugs (Abilify, Seroquel XR) that have received new indications for “add-on” treatment; existing drugs (Silenor, Nuedexta, Kapvay) that have been tweaked and reformulated for new indications; and new drugs (Invega, Oleptro, Invega Sustenna) whose major attraction is a fancy, novel delivery system.

Testing and approval of the above compounds undoubtedly cost billions of dollars (investments which, by the way, are being recovered in the form of higher health care costs to you and me), but the benefit to patients as a whole has been only marginal.

The true crisis, in my mind, is that with each new drug we psychiatrists are led to believe that we’re witnessing the birth of a blockbuster.  Not to mention the fact that patients expect the same, especially with the glut of persuasive direct-to-consumer advertising (“Ask your doctor if Pristiq is right for you!”).  Most third-party payers, too, are more willing to pay for medication treatment than anything else (although—thankfully—coverage of newer agents often requires the doctor to justify his or her decision), even though many turn out to be a dud.

In the meantime, this focus on drugs neglects the person behind the illness.  Not every person who walks into my office with a complaint of “depression” is a candidate for Viibryd or Seroquel XR.  Or even a candidate for antidepressants at all.  But the overwhelming bias is that another drug trial might work.  “Who knows—maybe the next drug is the ‘right’ one for this patient!”

Recently, I’ve joked with colleagues that I’d like to see a moratorium on psychiatric drug development.  Not because our current medications meet all of our needs, or that we can get by without any further research.  Not at all.  But if we had, say, five years with NO new drugs, we might be able to catch our collective breaths, figure out exactly what we’re treating after all (maybe even have a more fruitful and unbiased discussion about what to put in the new DSM-5), and, perhaps, devote resources to nonpharmacological treatments, without getting caught up in the ongoing psychopharmacology arms race that, for many patients, focuses our attention where it doesn’t belong.

So it looks like my wish might come true.  Maybe we can use the upcoming slowdown to determine where the real needs are in psychiatry.  Maybe if we devote resources to community mental health services, to drug and alcohol treatment, pay more attention to our patients’ personality traits, lifestyle issues, co-occurring medical illnesses, and respond to their goals for treatment rather than AstraZeneca’s or Pfizer’s, we can improve the care we provide and figure out where new drugs might truly pay off.  Along the way, we can spend some time following the guidelines discussed in a recent report in the Archives of Internal Medicine, and practice “conservative prescribing”—i.e., making sensible decisions about what we prescribe and why.

Sometimes, it is true that less is more.  When Big Pharma backs out of drug development, it’s not necessarily a bad thing.  In fact, it may be precisely what the doctor ordered.

22 Comments | business, marketing, medications, psychopharmacology | Tagged: , , , , , | Permalink
Posted by stevebMD

The Balance of Information

May 19, 2011

How do doctors learn about the drugs they prescribe?  It’s an important question, but one without a straightforward answer.  For doctors like me—who have been in practice for more than a few years—the information we learned in medical school may have already been replaced by something new.  We find ourselves prescribing drugs we’ve never heard of before.  How do we know whether they work?  And whom do we trust to give us this information?

I started to think about this question as I wrote my recent post on Nuedexta, a new drug for the treatment of pseudobulbar affect.  I knew nothing about the drug, so I had to do some research.  One of my internet searches led me to an active discussion on a site called studentdoctor.net (SDN).  SDN is a website for medical students, residents, and other medical professionals, and it features objective discussions of interesting cases, new medications, and career issues.  There, I found a thread devoted to Nuedexta; this thread contained several posts by someone calling himself “Doogie Howser”—and he seemed to have a lot of detailed information about this brand-new drug.

Further internet sleuthing led me to a message board on Yahoo Finance for Avanir Pharmaceuticals, the company which makes Nuedexta.  In one of the threads on this board, it was suggested that the “Doogie Howser” posts were actually written by someone I’ll call “TS.”  Judging by the other posts by this person, “TS” clearly owns stock in Avanir.  While “TS” never admitted to writing the SDN posts, there was much gloating that someone had been able to post pro-Nuedexta information on a healthcare website in a manner that sounded authoritative.

Within 24 hours of posting my article, someone posted a link to my article on the same Yahoo Finance website. I received several hundred “hits” directly from that link.  Simultaneously (and ever since), I’ve received numerous comments on that article, some of which include detailed information about Nuedexta, reminiscent of the posts written by “Doogie Howser.” Others appear to be written by “satisfied patients” taking this drug.  But I’m skeptical. I don’t know whether these were actual patients or Avanir investors (or employees); the IP address of one of the pro-Nuedexta commenters was registered to a public-relations firm in Arizona. Nevertheless, I have kept the majority of the posts on the blog, except those that contained personal attacks (and yes, I received those, too).

The interesting thing is, nothing “TS”/”Doogie Howser” said about Nuedexta was factually incorrect.  And most of the posts I received were not “wrong” either (although they have been opinionated and one-sided).  But that’s precisely what concerns me. The information was convincing, even though—if my hunch is correct—the comments were written for the sake of establishing market share, not for the sake of improving patient care.

The more worrisome issue is this: access to information seems to be lopsided.  Industry analysts (and even everyday investors) can have an extremely sophisticated understanding of new drugs on the market, more sophisticated, at times, than many physicians.  And they can use this sophistication to their advantage. Some financial websites and investor publications can read like medical journals.  Apparently, money is a good motivator to obtain such information and use it convincingly.  Quality patient outcomes? Not so much.

So what about the doctor who doesn’t have this information but must decide whether to prescribe a new medication?  Well, there are a few objective, unbiased sources of information about new drugs (The Medical Letter and The Carlat Report among them).  Doctors can also ask manufacturers for the Prescribing Information (“PI”) or do their own due diligence to learn about new treatments.  But they often don’t have the time to do this, and other resources (like the internet) are far more accessible.

However, they’re more accessible for everyone.  When the balance of information about new treatments is tipped in favor of drug manufacturers, salespeople, and investors—all of whom have financial gain as their top priority—and not in favor of doctors and patients (whose lives may be at stake), an interesting “battle of wits” is bound to ensue.  When people talk a good game, and sound very much like they know what they’re talking about, their motives must always be questioned.  Unfortunately—and especially under the anonymity of the internet—those motives can sometimes be hard to determine.  In response, we clinicians must be even more critical and objective, and not necessarily believe everything we hear.

15 Comments | computers, marketing, medications | Tagged: , , , | Permalink
Posted by stevebMD

Horizant: The Second Coming of Gabapentin

April 8, 2011

Like the religious notion of reincarnation, apparently some drugs are destined to be reborn as newly designed and re-packaged drugs for brand new indications.  I’ve written about Contrave and Silenor, for instance—two drugs with generic equivalents that have been re-tweaked, re-packaged, and renamed, for newer (and larger) markets.

This week, the FDA granted its approval to yet another “new” agent (that’s “new” with an asterisk, mind you), Horizant, developed by GlaxoSmithKline (GSK) and Xenoport.  Horizant is a name-brand version of gabapentin, which is also known as Neurontin.  While on the surface this appears to be an attempt to re-brand an existing drug, it may actually provide some advantages over the already-available alternative.  But the question is, at what cost?  And for what exactly?

Gabapentin was approved in 1994 and is marketed as Neurontin.  It’s approved for the treatment of partial seizures and post-herpetic neuralgia (although its manufacturer, Pfizer, got into some serious trouble for extensive off-label marketing of this compound—so what else is new?).  These days, it’s actually quite widely used by neurologists and psychiatrists, not just for seizures, but also for  chronic pain syndromes, anxiety, mood stabilization (where it’s not particularly effective), and even for alcohol dependence.

Gabapentin’s bioavailability—the ability of the drug to enter the bloodstream when taken as an oral dose—is rather low (and, paradoxically, decreases as the dose is increased) and the duration of its action is quite short, which means that users need to take this drug three or four times daily.  The key advantage of Horizant is that it is a “pro-drug.”  Technically it’s gabapentin enacarbil, and the “enacarbil” refers to a molecule added to the drug which allows it to be absorbed along the entire GI tract, resulting in greater blood levels.

(Interestingly, in early 2010 the FDA rejected Horizant’s first request for approval, citing a small but significant risk of cancer.  They relented, however, and approved it this year after “reconsidering the risks and benefits.”  Sound fishy?  No, I’m sure it’s all good.)

So who might use Horizant?  Well, you can bet that GSK and Xenoport hope that anyone who currently uses Neurontin (and there are a lot of them) is a potential customer patient.  Officially, though, it was approved for the treatment of restless legs syndrome (RLS).

Now, RLS is one of those “diseases that may not be diseases”—or “diseases that you didn’t know you had.”  (See the articles here and here for accusations of “disease mongering” by GSK [hey! GSK! Coincidence? I don’t think so!] when it introduced Requip, the first “treatment” for RLS.)  Hopefully it goes without saying that when you see headlines like “Disease X may affect  7-10% of the population” when, in fact, no one had even heard of Disease X ten years ago, you have to be somewhat suspect.

Nevertheless, like much else in psychiatry, there may be some reality to RLS; it may in fact be a true pathophysiological entity that responds to medication.  (Whether this entity afflicts 10% of the population is another story.)  Current treatment strategies involve dopamine replacement, in the form of Requip (ropinirole) or Mirapex (pramipexole) so maybe dopamine insufficiency is part of the process.

The symptoms of RLS are “an urge to move the limbs, which improves with activity and worsens with rest.”  That’s about it.  Which leads to yet another problem (a problem that GSK and Xenoport don’t see as a problem, that’s for sure): with such nonspecific and common symptoms (who among us hasn’t felt somewhat restless, with interrupted sleep?), a lot of people might get diagnosed with RLS when their symptoms are actually due to something else.

I thought of this a few weeks ago, when I saw that the RLS “patient page” on the National Institutes of Health (NIH) web site referred to RLS as “akathisia” (thanks to altmentalities for the link).  Akathisia (from the Greek for “not sitting still”) has long been recognized as a side effect of some—perhaps most—psychiatric medications, from antipsychotics to antidepressants.  It is often described as an “inner restlessness,” a “need to keep moving.”  Sometimes it’s associated with extreme emotional distress.  In terms of severity, it can range from a mild nuisance to—in some cases—aggressive tendencies.  (Indeed, the psychiatrist David Healy has even linked psychotropic-induced akathisia to suicide attempts and violent behavior.)

Psychiatrists really don’t know exactly what causes akathisia, and disagree on how to treat it.  It may have something to do with dopamine blockade, or something completely independent.  Treatment might consist of benzodiazepines (like Ativan or Valium), beta blockers (like propranolol), or discontinuing the drug that caused it in the first place.

Unlike RLS, which seems to bother people most when they are lying down (hence its tendency to disrupt sleep), drug-induced akathisia is worse when people are awake and moving around.  Sounds like a simple distinction.  But nothing is quite this simple, particularly when psychiatric drugs—and real people—are involved.   In fact, many psychiatric meds can cause other motor side effects, too, involving (theoretically) yet other neural pathways, such as “parkinsonian” side effects like rigidity and tremor.  (In fact, some antipsychotic drug trials show “restlessness” and “akathisia” as entirely separate side effects, and when I’ve tried to ask experts to explain the difference, I have never received a straightforward answer.)

So what does this all mean for Horizant?  I could be cynical and simply remark that GSK/Xenoport are capitalizing on the nonspecificity of symptoms, the tremendous diagnostic overlap, and the fact that motor side effects, in general, are common side effects of antipsychotics (one of the most widely prescribed drug classes worldwide).  In other words, they know that there are a lot of people out there with “restless legs” for all kinds of reasons, and lots of psychiatrists who will misdiagnose akathisia as RLS and prescribe Horizant for this purpose.  But in reality, that remark would not be all that cynical.  Remember, there is this pesky little thing called “return on investment.”

What it means for the patient (or should I say “customer”) is more confusing.  A new agent with apparently better availability and kinetics than gabapentin is now available, but approved for the treatment of something that may or may not exist (in most patients), and may or may not be more effective than gabapentin itself.  Oh, and a hefty price tag, too.  Ah, the wheels of psychopharmacology keep turning….

(NB: altmentalities has also written her point of view on the Horizant story… I suggest you check it out, too.)

96 Comments | marketing, medications, psychiatry | Tagged: , , , , , , , | Permalink
Posted by stevebMD

Thank You, Somaxon Pharmaceuticals!

March 18, 2011

One year ago today, the pharmaceutical company Somaxon introduced Silenor, a new medication for the treatment of insomnia, and today I wish to say “thanks.”  Not because I think Silenor represented a bold new entry into the insomnia marketplace, but because Somaxon’s R&D and marketing departments have successfully re-introduced doctors to a cheap, old medication for a very common clinical complaint.

You see, Silenor is a branded version of a generic drug, doxepin, which has been around since the 1970s.  Doxepin is classified as a tricyclic antidepressant, even though it’s not used much for depression anymore because of its side effects, mainly sedation.  Of course, in psychiatry we sometimes exploit the side effects of certain drugs to treat entirely different conditions, so it’s not surprising that doxepin—which has been generic (i.e., cheap) for the last few decades—has been used occasionally for the treatment of insomnia.  However, this is an “off-label” use, and while that doesn’t prevent doctors from prescribing it, it may make us less likely to consider its use.

Somaxon spent several years, and millions of dollars, developing Silenor, a low-dose formulation of doxepin.  Stephen Stahl (paid by Somaxon) even publicized low-dose doxepin in his CNS Spectrums column.  Generic doxepin is currently available in comparatively high doses (10, 25, 50, 75, 100, and 150 mg), but Somaxon found that lower doses (6 and 3 mg, even 1 mg) can be used to treat insomnia.  Silenor is sold at 3 and 6 mg per tablet.

The obvious question here (to both expert and layman alike) is, what’s so special about the 3 or 6 mg dose?  Why can’t I just take a generic 10 mg pill and cut it in half (or thereabouts), for a homemade 5-mg dose?  Well, for one thing, the 10 mg dose is a capsule, so it can’t be split.  (There is a generic 10 mg/ml doxepin solution available, which would allow for very accurate dosing, but I’ll ignore that for now.)

Okay, so there’s the practical issue: pill vs. capsule.  But is 6 mg any better than 10 mg?  For any drug, there’s always variability in how people will respond.  The relative difference between 6 and 10 is large, but when you consider that people have been taking doses of up to 300 mg/day (the maximum approved dose for depression) for decades, it becomes relatively meaningless.  So what gives?

It’s natural to ask these questions.  Maybe Somaxon was hoping that doctors and patients simply assume that they’ve done all the necessary studies to prove that, no, doxepin is an entirely different drug at lower doses, and far more effective for sleep at 3 or 6 mg than at any other dose, even 10 mg.  Indeed, a few papers have been published (by authors affiliated with Somaxon) showing that 3 and 6 mg are both effective doses.  But they still don’t answer:  how are those different from higher doses?

I contacted the Medical Affairs department at Somaxon and asked this very question.  How is 3 or 6 mg different from 10 mg or higher?  The woman on the other end of the line, who (one would think) must have heard this question before, politely responded, “Doxepin’s not approved for insomnia at doses of 10 mg or higher, and the 3 and 6 mg doses are available in tablet form, not capsule.”

I knew that already; it’s on their web site.  I would like to think that no psychiatrist asking my question would settle for this answer.  So I asked if she had some additional information.  She sent me a six-page document entitled “Is the 10 mg Doxepin Capsule a Suitable Substitute for the Silenor® 6 mg tablet?”  (If you’re interested in reading it, please email me.)

After reading the document, my response to this question is, “well, yes, it probably is.”  The document explains that doxepin hasn’t been studied as an insomnia agent at higher doses (in other words, nobody has tried to get FDA approval for doxepin in insomnia), and the contents of the tablet are absorbed at a different rate than the capsule.

But what really caught my eye was the following figure, which traces plasma concentration of doxepin over a 12-hour period.  The lower curve is for 6 mg of Silenor.  The higher curve is for “estimated” 10 mg doxepin.

Huh?  “Estimated”?  Yes, that’s right, the upper curve was actually obtained by giving people 50 mg doxepin capsules and then “estimating” the plasma concentrations that would result if the person had actually been given 10 mg capsules.  (I know, I had to read it twice myself.)  I don’t know how they did the estimation.  Did they divide the plasma concentration by 5?  Use some other equation involving fancy things like logarithms or integrals?  I don’t know, and they don’t say.  Which only begs the question: why didn’t they just use 10 mg capsules for this study???

That seems a little fishy.  At any rate, their take-home message is the fact that with the lower dose, there’s less doxepin left over in the bloodstream after 8 hours, so there’s less of a “hangover” effect the next morning.  But this just raises even more questions for me.  If this is the case, then what about all those people who took 75-150 mg each day for depression?  Wouldn’t that result in a constant “hangover” effect?  I didn’t practice in the 1970s and 1980s, but I’m guessing that depressed people on doxepin weren’t in bed 24 hours a day, 7 days a week.  (I know, the serotonergic and noradrenergic effects “kick in” at higher doses, but the histamine and alpha-1 adrenergic receptors are already saturated.)  A related question is, what plasma concentration of doxepin is required to induce sleep anyway?  What plasma concentration accounts for a “hangover” effect?  0.5?  1.0?  2.0?  Does anyone know?

The Somaxon document states that “clinical trials demonstrated only a modest increase in mean sleep maintenance efficacy when the dose is increased from 3 mg to 6 mg.”  But according to the graph above, the 3 mg curve would be expected to look quite different, as it’s a 50% reduction in dose.  (And I can’t even begin to think what the 1 mg curve would look like, but that apparently works, too.)

We all know (or should know) that tables, charts, and graphs can be used to convey just about any message.  It’s important to look at which data are presented, but also which data are not presented, in order to draw any conclusions.  We must also ask what the data actually mean (i.e., the importance of a plasma concentration—what does it actually mean for a clinical effect?).  In the end, Somaxon’s “explanation” seems like a pretty flimsy explanation for using a very expensive name-brand drug.

That said, I do have to say “thank you” to Somaxon for reminding me of yet another medication that I can use to help treat insomnia.  Not Silenor, but low-dose generic doxepin (10 mg).  It’s a shame they had to spend the millions of dollars on R&D, clinical trials, and marketing, to convince me to prescribe the generic version of their drug, which costs only pennies a pill, but then again, you pays your money, you takes your chances.

(Postscript:  Speaking of money, Somaxon stock closed at $2.70/share today, down from a high of $10.01 on the day Silenor was approved, a loss of $258 million of market capitalization.  Imagine all the soft pillows, soothing music CDs, and OTC sleep aids that money could have bought…)

42 Comments | insomnia, marketing, medications, psychopharmacology | Tagged: , , , , , | Permalink
Posted by stevebMD

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