Thursday, April 16, 2015

How a New Blood Test for Depression is like Apple Recognition

Four years ago I wrote a blog post about the MDDScore blood test for depression. That was before there were any peer-reviewed publications describing it. Now there are at least two. The latest came out a couple of months ago in the Journal of Clinical Psychiatry, and you can access the article, along with two interesting commentaries, for free.

While I won't go into the article in any detail, suffice it to say that the overall accuracy of the test for diagnosing depression was between 91% to 94%, depending on the group studied. Based on this, the authors report that the test "has excellent performance in confirming a diagnosis of MDD (major depressive disorder)."

The article is a classic example of the pitfalls of focusing on glitzy-sounding statistics while downplaying the actual clinical usefulness, which in this case is close to nil, as both of the Journal's commentators agreed.

I recently discussed the same problem in an article I wrote for CCPR about the NEBA EEG test for ADHD. Like the MDDScore, the NEBA test promises to aid in the diagnosis of a psychiatric illness. The NEBA's accuracy is high, with a positive predictive value for ADHD of 96% for kids, and 81% for adolescents. But no matter how accurate it is, the crucial question is whether it adds value above and beyond the standard psychiatric interview. Neither the MDDScore nor the NEBA do.

In my article, I used a hypothetical analogy of a new test to diagnose apples:

"Let’s imagine that there’s a new apple-recognizing device on the market called the “Apple Rec,” which uses various technologies to measure the wavelength of light reflected by an object, its mathematical curvature, etc. The manufacturer provides impressive data showing that the Apple Rec has 100% sensitivity and 100% specificity for diagnosing (recognizing) an object as being an apple. Given these dazzling statistics, would you buy the Apple Rec? No, because even though it’s exquisitely accurate, it provides you with no useful diagnostic information beyond what you can obtain by looking at the apple yourself. However, if the Apple Rec provided you with added value, you might consider it a good investment. For example, if, in addition to correctly recognizing it as an apple, it also calculated its sweetness and crispness, the Apple Rec suddenly becomes a useful tool, because these are qualities that you would otherwise struggle to ascertain."

The apple principal applies to diagnostic tests in psychiatry. Before you refer your patients to an expensive test that diagnoses ADHD, depression, or anything else, you need to make sure that it does something that you can’t easily do yourself.  

Wednesday, April 15, 2015

Medscape Presents: The Brintellix Show

As I wrote in part one of my Medscape review, the website gets high marks for up-to-the-minute coverage of psychiatric news, and it deserves kudos for posting a ton of textbook-like content on disorders and drugs. I wasn’t so thrilled with its "un-privacy" policy, which results in your personal info and browsing history being sold to third parties. 

Today we get into the dark side of Medscape Psychiatry, which is their industry-funded CME. 

Medscape Psychiatry CME Overview

Medscape offers four different categories of CME on its “CME and Education” page.  "Clinical Briefs" and "Journal Articles" are mostly not industry funded, whereas "Patient Cases" and "Knowledge and Practice" are generally industry products.  

Brintellix (vortioxetine) Background

To give you a little context, Brintellix is the latest antidepressant to be FDA approved. It is being marketed as a "multimodal" antidepressant because it has effects on several different receptor sites. The company has produced some interesting data showing that Brintellix may cause fewer sexual side effects than other antidepressants, and that it may help improve the slowed-down thinking that is common with depression. But it is not FDA approved for either of these potential advantages, because thus far, the data are far from definitive.

Medscape and Takeda/Lundbeck

Medscape is the largest single recipient of pharmaceutical CME grants among all U.S. medical communications companies. According to an article in JAMA, it received $20,315,730 in 2010, the last year for which such data were aggregated. I don't know how much the company is receiving from Takeda/Lundbeck for producing CME programs, but it's probably a lot. If you click through Medscape's most technologically sophisticated online courses, a high proportion are funded by this duo.

Here are some of the titles of the courses:

Commercial Bias in One of the Courses

All of the courses listed above are likely biased in favor of Brintellix--there wouldn't be much point in paying Medscape to produce them otherwise. Since blogging is not my day job, I chose only one of them to watch: The Pharmacology of MDD Treatment: Building a Foundation With a Focus on 5-HT.

This course begins with four multiple choice questions, which are supposed to test your knowledge before you learn. Here's one of them:

Which of the following antidepressants manipulates the most serotonin receptors at once?
The correct answer? Vortioxetine. 

This is a clever way to prime the pump, to get the audience thinking about the promoted drug.

Next, we get a slide purporting to give an overview of the history of antidepressant drug development.

The big red bubble labeled MMD refers to "multimodal drug", ie., vortioxetine. That's the latest one. The implication is that it's the most technically advanced. 

Later in the program, there are a few slides highlighting "new antidepressants." Only one antidepressant gets prominently featured on two slides:

The more crucial question is not "how many ways can one drug manipulate 5-HT" (even the manufacturer states the "clinical relevance" of the drug's many serotonin actions is "unknown") but rather "how many ways can one communication company manipulate doctors's prescribing practices?"

To make their point crystal clear, one of the experts in the video glowingly endorses Brintellix, saying that its multimodal mechanism is like packing a bunch of great medicines into one:

"Vortioxetine is a great example of this multimodal thing we were talking about. It is a serotonin reuptake inhibitor, but it also is a very strong agonist at 5-HT1A, which we said you want to have an agonist there. It also is a powerful antagonist at 5-HT3 which and a powerful antagonist at 5-HT7. On paper, here is a drug that has some of these qualities we have been talking about that could make it possibly a multimodal agent almost like a built in augmentation strategy in 1 pill, which certainly would be, just practically, a little easier for patients than having to take more than 1 medicine, which we often have to do.[3-6]"

A bit later, he goes even further, implying that Brintellix uniquely targets three common symptoms of depression:

"Again, right now, the data clearly show the 3 most common residual symptoms, even with people who have a response to an antidepressant are insomnia, cognitive impairment, and fatigue. I think those are things that are not well addressed by an SSRI alone. Thinking more sophisticated, multimodal actions whether it is 1 pill that has that built in augmentation. I think that is where the field is going."
Summing up Medscape
Since the last time I reviewed a psychiatric website, I assigned a letter grade, I'll give Medscape one as well: a B-. 
Why? It gets an A for delivering bite-sized psychiatric news clips on its non-CME page, an A- for providing free but dry drug and disorders info, and an F for failing to comply with Standard 5 of ACCME's Standards for Commercial Support in its CME courses. Among other things, Standard 5 forbids a CME program from promoting a "specific proprietatry business interest of a commercial interest", and it requires that presentations "must give a balanced view of therapeutic options." 
I'm surprised that Medscape is still resorting to these shenanigans, but I guess that's what butters their bread. 

Wednesday, April 8, 2015

Medscape Psychiatry Review, Part One: The Good...

Medscape is the number one website for American physicians--a 2010 survey found that 57% of doctors read the site. I'll wager that proportion is higher in 2015.

I have not always been Medscape's number one fan. I've called the site out for pushing Cymbalta in a Lilly-funded "Pain TV" program and for touting Invega in a CME-accredited infomercial that was so blatant that Business Week ran a story about it.

But I have found that the site has improved over the past few years. For example, gone are the notorious sponsored resource centers, in which a single company would underwrite all coverage of a disorder (eg., Shire bought the ADHD section, and GlaxoSmithKline bought bipolar disorder.) There are plenty of ads, but Medscape appears to have understood the separation between church and state, and has stopped merging ads with least in their main pages.

So if you are a psychiatrist browsing for some reliable, free information, can you rely on Medscape? I'll give a qualified "yes."

Where Medscape really excels is in bringing up-to-date news written in an unbiased journalistic style.

For example, above is the psychiatry homepage from April 7, 2015. Yes, there is a big positive feature on a heavily promoted antipsychotic agent, Latuda. But there’s also an article praising lithium as an effective and underused generic drug. And there's a piece about how antidepressants can cause seizures even at normal doses. So at least on the homepage, Medscape is no longer the shill for drug companies that it once was.

If you drill into specific topics, you’ll also find that Medscape becomes a gigantic encyclopedia of medical knowledge. It covers all specialties, and in the psychiatry section alone there are over 100 articles. The articles have multiple sections and are comprehensive. They remind me of the truck-sized psychiatry textbooks that most of us felt we needed to buy earlier in our careers but which we have rarely cracked open. Like those textbook chapters, Medscape’s educational articles are quite dry – even, at times excruciatingly boring. But, nonetheless, the information is out there for you to read and it is scot-free.

Unfortunately, there are still a few dark sides to Medscape. A 2013 article in JAMA authored by Sheila Rothman and colleagues alerted all physicians to the fact that Medscape, along with other similar medical communication companies, is in the business of sharing all of your personal data with drug and device companies. You can read Medscape’s privacy policy here. It's a long document but I will give them credit for using pretty plain language as they disclose the myriad ways in which they are sharing your information. One of the creepiest technologies is called a "web beacon." This is a hidden drone of the Internet that tracks every click you make, every page you seek, and every breath you take. Your mental processes are then sold to "third parties". It's absolutely creepy.

Some will object that this is business as usual on the web. Google does it, which is why I see ads popping up in my gmail for an obscure car rack that I searched for last month. Tracking my car rack searching behavior is one thing--tracking how I'm thinking about saving patients' lives...well, I think there's a qualitative difference. 

In part two of my Medscape post I will cover their continued addiction with industry funded CME. I guess that pays their bills. But the crassness of these infomercials is pretty astonishing, particularly in the era of the Physician Payment Sunshine Act. To be continued…

Wednesday, April 1, 2015

Psychiatry Website Review: Rajnish Mago's "Simple and Practical Mental Health"

Lately I've been browsing for good psychiatry websites to harvest ideas for an upcoming redesign of The Carlat Psychiatry Report. Everything's fair game in my search, whether industry-funded or not. I'm not going to try to pretend that industry funding inevitably leads to tainted information. Clearly, sometimes it does, but sometimes it doesn't.

I've been finding a lot of quality information out there, much of it for free. So I'll spend the next few posts reviewing some of these sites.

One of the very best is called "Simple and Practical Mental Health" by Rajnish Mago, who is the director of the Mood Disorders Program at Thomas Jefferson University Medical College in Philadelphia. The website is oriented toward prescribing mental health practitioners, though I'd imagine both therapists and consumers would find the information helpful. The site itself doesn't appear to be funded by industry, though Dr. Mago does work with industry (see below).

The really great thing about Dr. Mago is his informal style of laying out information--without excessive jargon. For example, here is how he starts an article about omega-3 fatty acids:

"Do you routinely ask your patients with some form of clinical depression (depressive disorders) or bipolar disorder to take an omega-3 fatty acid supplement? If not, why not? There is data to support use of such supplementation as an adjunct in the treatment of these disorders. 
However, many clinicians may not be clear about which  omega-3 fatty acids to recommend, inwhat ratio, and in what dose. While there is more to learn about this topic, here is some practical information about how to get started in recommending this supplement:"
And then he goes on to give some extremely practical advice on how to decide which fatty acids to prescribe, what the doses should be, and so on. 

While the site is free, he does use it to sell a couple of books, both of which I bought. They're both excellent, but the better of the two is "Side Effects of Psychiatric Medications," which is chock full of down to earth clinical advice about preventing and managing side effects. This is not a particularly sexy topic in psychiatry, but it's important, so it's nice to see that a very smart clinician has put a lot of thought into it. 

I do have a couple of critiques: 

1. There is no clear link to his financial disclosures. He does list them on the site, but the page is almost impossible to find. I had to do a google search which brought me to a link on a different website which then looped me back to a page on the original site. Dr. Mago works with pharma, doing both research and consulting. Nonetheless, the site doesn't seem to be pushing any particular drug, though there is a pro-diagnosis feel to a lot of the articles, which might be seen as disease-mongering by those particularly sensitive to the issue. In his case, my sense is simply that he genuinely believes many psychiatric disorders are under-diagnosed. 

2. There is no search bar, so you have to rely on menu navigation to find anything. 

Overall, I give the site an A-, downgraded only because of the above two issues. Keep it up, Dr. M!

Tuesday, March 24, 2015

The Atlantic Slams Alcoholics Anonymous--The Carlat Take

The current issue of The Atlantic magazine has a fascinating article entitled "The Irrationality of Alcoholics Anonymous." In a wide-ranging and well-researched article, the author Gabrielle Glaser, begins with the story of a lawyer identified as "J.G."

"J.G." began drinking at age 15 and his habit ramped up through college and law school. Ironically, much of J.G.'s law practice is defending drunk drivers. On a typical court day, according to the article, he would start drinking after his first morning court appearance, and he bought himself a Breathalyzer to make sure he didn't end facing the same judge as his clients. At his worse, he was drinking a full liter of whiskey per day.

Eventually he checked into a rehab based on AA principles. AA famously maintains that complete abstinence is a requirement of effective treatment. It didn't work for J.G., and only led to a series of miserable white-knuckled periods of sobriety interspersed with relapses. Toward the end of the long article we learn that (spoiler alert) J.G. finally gets himself into a clinic that acknowledges the scientific evidence of the efficacy of medications for alcoholism. He is prescribed baclofen and the occasional Valium, and is now successfully sober.

In The Carlat Addiction Treatment Report (CATR) we've written at length about AA and we're generally in agreement with this article. The Cochrane Collaboration, which synthesizes the best evidence available, found only eight RCTs of adequate quality that looked at AA or 12-step Facilitation (TSF), the professional treatment approach that strongly encourages AA participation. The resulting meta-analysis concluded, “No experimental studies unequivocally demonstrated the effectiveness of AA or TSF approaches for reducing alcohol dependence or problems” (Ferri M et al, Cochrane Database Syst Rev 2006;3:CD005032).

The Atlantic article's timing was perfect for CATR as we just published an issue devoted to integrating medications and therapy in alcoholism treatment. You can read the article on pharmacotherapy for free here

The bottom line is that AA likely works for many people, particularly those who become active in meetings and who get a sponsor. But we know from placebo controlled trials that medications such as naltrexone and acamprosate are effective--and there's no reason not to combine meds with a 12-step program or psychotherapy. 

Saturday, March 21, 2015

On Combining Antipsychotics, Top-Performing Therapists, and Procrastination

I woke up this morning and realized that I've allowed myself to become a victim of BPS--Blog Procrastination Syndrome. It happens to the best of us. We write a post, and days and weeks and months go by. "My next post has to be really, really good," we think.

Forget that. I'm just going to dive back in beginning today. "Done is better than perfect," someone once told me.

At The Carlat Psychiatry Report, we are busy planning future issues, and here are a couple of upcoming topics that I'm fired up about.

Combining Antipsychotics. 

Psychiatrists have gotten plenty of bad PR about our use of antipsychotics. And some of that bad PR is justified. We overuse Seroquel as a sleeping pill. We add too much Abilify to antidepressants because patients come into our office having been hypnotized by ads telling them that this is the drug that will finally help them kick their blues.

But sometimes the criticism is misguided. Lately, guidelines have been published discouraging us from combining antipsychotics. "That's not evidence-based practice," we're told. Fair enough. But when your patient on risperidone is still digging through the snowbanks looking for the transmitter that he's convinced is causing the world to hurtle toward oblivion, you need to something. You can increase the dose, you can switch, you can add, etc....

So I'm working with psychiatric pharmacist Kelly Gable on an article that says, "Look, we understand that combining antipsychotics can increase side effects and is not supported by randomized controlled trials. But sometimes we do it anyway, because our patients our suffering."

We're collecting a list of scenarios that typically lead to antipsychotic polypharmacy, and we're going to evaluate how reasonable these scenarios are. If you have any experience, positive or negative, with antipsychotic polypharmacy, please let me know by email or by commenting to this post.

Top Performing Therapists. 

I interviewed Scott Miller, PhD, the other day for our April issue on psychotherapy. Dr. Miller believes that the real key to improving our clinical success is systematically getting feedback from our patients on how well therapy is going (or medication treatment, or combined treatment, etc....).

He's also found that top performing clinicians spend three to four and a half times as many hours per week than others engaging in "deliberate practice". What does that mean?  You'll have to read about it in the issue. I'm still editing the interview and really enjoying it.

Phew. Feels good to clear out some of the blog-webs that have developed over the months. See you again soon. Really.

Thursday, November 6, 2014

Exploring the link between industry payments to doctors and prescribing habits

This article was originally published in The BMJ on November 5, 2014.

Orthopedic surgeons receive the biggest payments from industry in the US according to the Open Payments database. The next step, writes transparency pioneer Danny Carlat, is for researchers to compare payment data with disclosures of physicians’ prescribing patterns 

After substantial delays, the Open Payments website was launched on 30 September.1 The website was mandated by the Physician Payments Sunshine Act of 2010, and it is a comprehensive registry of payments made to physicians and teaching hospitals by drug and device companies. 

This first wave of reports must be interpreted in light of some data limitations and technical problems. These reports cover only the last five months of 2013, and roughly a quarter of industry payments were not published because of disputed amounts and other factors. Of the payments published, a third have been stripped of the doctors’ names because there were problems ensuring that the payments were accurately attributed to the right recipient. Therefore, only about half of all payments are both published and attributed to identified recipients. The Center for Medicare and Medicaid (CMS), the agency in charge of the database, plans to roll out the missing payments in June of 2015, along with all payments made in 2014.

Although the website is not complete, it still provides unprecedented insight into the extent and nature of financial relationships between physicians and industry. In total, companies paid $3.5bn (£2.2bn; €2.8bn) to 546 000 physicians (about 60% of all US doctors) and to 1360 teaching hospitals over the five months. The largest payments, often in the millions of dollars, went to orthopedic surgeons for royalty payments for inventing or refining surgical products. However, most payments (84%) were small and were for meals and beverages (table).

Breakdown of $3.5bn payments made to US doctors in last five months of 2013
Reason for payment Amount ($)
Research 1.5bn
Physician investors/owners 1bn
General: 1bn
Royalties and licences 302m
Promotional speaking 203m
Consulting 158m
Food 93m
Travel and lodging 74m
Education 36m
Gifts 19m
Interestingly, over 90% of the 300 physicians who were most highly paid for speaking or consulting were men, who comprise only 68% of US doctors. There is no clear explanation for this gender disparity. Women are more likely to work in lower paying specialties such as internal medicine and pediatrics and are underrepresented in specialties that are often recruited by industry for consulting. For example, only 4% of orthopedic surgeons in the US are women.

Wider moves to change behaviour

The Sunshine Act is only a transparency initiative and does not regulate what doctors can or cannot receive. However, the new website has been launched within a broader context of increasing pressure to reform industry payments. Two states, Vermont and Massachusetts, have instituted outright bans on gifts and meals, although the Massachusetts law was repealed because of concerns that local restaurants were losing income. The state’s original gift ban law of 2008 was controversial because it prohibited companies from providing any meals of any value to healthcare practitioners outside a healthcare setting. 

For several years, many of the larger companies have published their own physician payment registries, most of which were required by settlements of lawsuits alleging illegal marketing practices. As these payments have been made public, several companies have decreased their spending for promotional talks, and one company, GlaxoSmithKline, is eliminating such payments altogether.

Like industry, the medical profession is regulating itself. In 2008, the Association of American Medical Colleges published strict conflict of interest recommendations for academic medical centers, which have responded by strengthening their policies. From 2008 to 2014, the percentage of medical schools that ban their faculty from giving promotional talks has increased from 4% to 49%; the percentage of schools banning gifts and meals has also risen sharply. Since 2007, the American Medical Students Association has tracked such conflict of interest metrics in scorecards, which it publishes annually ( 

Disclosure of payments to doctors is also becoming more common in Europe. The French government, for example, is implementing a disclosure requirement that is similar, though not quite as comprehensive, as the Sunshine Act. In the UK, payment disclosure is based on a voluntary system run by the Association of the British Pharmaceutical Industry, a drug company trade group. Unlike the case in both France and the US, the UK system allows physicians to opt out of disclosure. This opt out provision may prevent meaningful disclosure, depending on the proportion of physicians who use it. Patients may complain that they cannot look up their doctors, and researchers and journalists may have difficulty comparing an individual doctor’s payment with peer averages if the database is incomplete.

Research possibilities

How will the Open Payments database be helpful in the future? Although the Sunshine Act was ostensibly passed to allow consumers to make more informed healthcare choices, it is likely that the site will have even more value to researchers and policy makers. The degree to which industry payments actually influence medical care has not been resolved because until now there were scant data with which to properly investigate the issue. But researchers will now be able to compare a trove of industry payment data with other databases recently released by CMS, such as detailed disclosures of physicians’ prescribing patterns.

Even before Open Payments, one research group merged the prescribing database with industry payment data aggregated by the investigative journalism organization ProPublica. They found that payments were strongly correlated with increased prescriptions of companies’ products. Such results, if replicated on a larger scale, may well lead to stricter government regulation of financial relations between companies and physicians. Such regulations, in turn, would hopefully lead to more evidence based healthcare and improved patient outcomes. If so, Open Payments will turn out to be an enterprise well worth the effort.


Cite this as: BMJ 2014;349:g6651


  • Competing interests: I have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.
  • Provenance and peer review: Commissioned; not externally peer reviewed.