Wednesday, September 16, 2015

The Paroxetine Study 329 Re-Write

I've not really written about GlaxoSmithKline's infamous paroxetine (Paxil) Study 329, except to briefly allude to it in a previous post. This is probably because I felt others had covered it so extensively already, especially over at the 1boringoldman blog. Another anonymous child psychiatrist has an entire website summarizing the study, and there's even a detailed wikipedia page. So go to those sites if you haven't heard of this study before. However, I wanted to write this post to share my thoughts about the re-analysis of the study's data by an independent, mostly-international team, which was accepted for publication in the BMJ.

First off, I want to be clear that I don't think the new publication's results will be news for anyone in the profession who has been paying attention. In my years of practice (which admittedly are not many), I've never seen a young patient prescribed paroxetine by a child psychiatrist. While studying for a board exam the other day, I saw this (source):

If it's been covered in a textbook published in 2010, you can be sure it's pretty common knowledge by now. In this regard, the profession has been self-correcting. However, it seems that despite acknowledging the risks of paroxetine, the profession has turned a blind eye toward the actions of the psychiatrists who had helped popularize its use in kids in the first place. None of the well-known academics whose names are attached to the study have offered to retract the paper, and as far as I know, none have suffered professionally. In fact, one of them, Karen Dineen Wagner, was just elected president of the American Academy of Child and Adolescent Psychiatry (AACAP).

There have been efforts to address this issue within AACAP, most notably by 2 regional child psychiatry organizations, including the Northern California Regional Organization of Child and Adolescent Psychiatry (NCROCAP). Dr. Mickey Nardo, the brains behind and one of the authors of the Study 329 re-write, informed the AACAP Ethics Committee about the study's faults, and they initially seemed receptive.* However, those efforts went nowhere. At a recent AACAP annual meeting, I was chatting with an older child psychiatrist, who is a "Distinguished Fellow" of the organization and has been involved in AACAP affairs for decades. Somehow, the topic of NCROCAP came up. When I commented that they seemed to be an activist bunch, he replied, "Yes, probably too much so, which is not good for the group process."

Well, now we see the outcomes of this "group process." By prioritizing group harmony over doing the right thing, AACAP has invited outside intervention. This BMJ editorial accompanying the new publication, by Peter Doshi, is one of the most damning things I've ever read about institutional intransigence.* It'll be interesting to see how the organization reacts.

UPDATE: As I was finishing this blog post, I got the following email (New York Times article published around 6:30pm EST, email was sent around 6:34pm*):
Dear Members,

This week, The BMJ published a study, “Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence,” which reanalyzes data from a clinical trial performed in the late 1990s and published in JAACAP in 2001. The conclusions of this article contradict those of the original study. Please know that the Academy has been fully aware of the pending publication of this article by The BMJ.

Research provides the foundation for child and adolescent psychiatry’s knowledge base. The Academy encourages rigorous scientific design and methodology and supports the highest ethical and professional standards. We also believe it is essential that research be conducted within a strong framework of transparency and disclosure. As an organization, AACAP has been a leader in advocating for the positive changes that have taken place in the last decade in the relationship between the pharmaceutical industry and academic and professional associations.

As the leading national professional medical association dedicated to promoting the healthy development of children, adolescents, and families, through advocacy, education, and research, our response to The BMJ publication is as follows:
  • AACAP has the utmost respect for the The BMJ and we thank them for their continued efforts to further scientific knowledge and understanding.
  • AACAP supports transparency in clinical trial reporting and welcomes the RIAT initiative, which enables publicly available primary data to be reanalyzed and published as new, potentially revised reports.
  • JAACAP is a forum for scientific reporting and scholarly discussion. The scientific process builds on itself over time through a cycle of new research, analysis, and ongoing dialog. This process stimulates debate and moves the field forward toward a better understanding of critical issues.
  • As with most medical journals, JAACAP operates with full editorial independence. AACAP does not influence or direct decisions regarding specific publications. Furthermore, the statements and opinions expressed in JAACAP articles are those of the authors, and not necessarily those of AACAP, the editors, or the publisher. Inquiries about the articles and study in question should be addressed to their respective authors.
Moving forward, we will continue to monitor any developments and keep the membership informed of relevant information as it becomes available. Please direct any questions to the Communications Department via email at

Thank you for your continued support!

Paramjit T. Joshi, MD
President, AACAP
Like I said, this is gonna be interesting.

These sentences were added/edited after original publication for completeness.

Saturday, September 5, 2015

Who Controls the Future of Medical Knowledge? Part I

The recent discontent amongst physicians regarding the process of maintaining board certification in various specialties got me thinking about a broader question: how do doctors acquire new medical knowledge, especially after medical school? Which brings me to an even more critical question: who controls said knowledge?

I would argue that next to our ability to listen to and empathize with patients, the other most valuable aspect of the medical profession is our knowledge. Ever since the days of Hippocrates, medical knowledge has been transmitted from one doctor to another in essentially the same way. In medical school and residency, we attend lectures, read textbooks, study cases, answer Socratic questions posed by more experienced clinicians, and most importantly, learn by seeing numerous patients and accumulating experience. After graduating medical school, it seems that most doctors learn by conferring with one another, reading journals, and attending conferences.

But the more information there is, the more time it takes to access and acquire new knowledge, and the harder it becomes for individual physicians to keep up.

You can be sure that corporations are well aware of this. On the patient side, of course, Dr. Google already provides incredible ease of access to knowledge and profits handsomely from selling ads to consumers. Pharmaceutical companies know more about my prescribing practices than I do, which fuels their targeted marketing efforts. More ambitiously, IBM's Watson Health Cloud promises to "bring together clinical, research and social data from a diverse range of health sources, creating a secure, cloud-based data sharing hub, powered by the most advanced cognitive and analytic technologies." And as much as I panned athenahealth's advertising in an earlier post, the electronic medical record companies will certainly find clever ways of profiting from the vast troves of health care data that they accumulate. And doctors are paying for the privilege of providing that information to them!

At least SERMO ("the most trusted and preferred social network for doctors") pays doctors for completing surveys, but you can be sure that they're in the same game. They keep their service free by monetizing the attention and knowledge of doctors: "Organizations seeking physician expertise, such as pharmaceutical companies, medical device firms, and biotechs, underwrite the market research and sponsorship opportunities within our site."

So what options are available for doctors who want to share their knowledge with each other free from the confines of a data mining operation? Of course, we can still consult with colleagues the old fashioned way, either in person or by phone. But after having these conversations, the knowledge still resides in the brains of people, not easily accessible to future doctors who may run into similar situations. Our professional associations post practice guidelines that hardly anyone reads, and at annual meetings, there are opportunities to meet with expert clinicians to discuss cases, which seems terribly inefficient. What about higher-tech options? There are numerous subscription services that provide summaries of research studies, but I believe that the patients doctors see do not necessarily resemble those who sign up for clinical trials. There are electronic mailing lists in which doctors can discuss cases, and which allow members to search through previous conversations. And there's wikidoc, a free wikipedia for doctors. However, these options are used by very few doctors and are paltry efforts next to the commercial ambitions of Big Data.

With all these business interests aiming to aggregate and profit from the knowledge of doctors, is there anything that the medical profession can do to avoid having our knowledge become some company's proprietary intellectual property?

I don't claim to have the answers, but I will explore some ideas in Part II. Stay tuned…

Friday, August 28, 2015

The Old Man: A Story

Part I

The first time I met the old man was during my residency interviews. He was spry and looked younger than his age, and why not? He was at the top of his game: head of a department, boatloads of research funding, one of the most well-known psychiatrists around. Another psychiatry department chair who had interviewed me previously hinted that the old man was quite a businessman and enjoyed cozy relations with industry.

As he asked me his first question, the old man practically winked: "So, are you single, in a relationship, or married, or what?" That was my first hint that he might not be the most ethically-inclined individual. I had been told by my medical school before interview season that such personal questions were definitely off limits. Yet he made his greeting seem like the most natural and friendly thing in the world.

Part II

The old man was fuming. He was supposed to be giving a talk on depression treatment, but what seemed to preoccupy his mind was a just-published study from Irving Kirsch suggesting that antidepressants were not better than placebo for mild to moderate depression. Our speaker seemed deeply and personally offended. After many words assailing Kirsch's motives, he concluded: "Even if it's no better than placebo, it doesn't mean we shouldn't treat the patient!" Almost sounded like advice from Allen Frances, but twisted.

Part III

By random chance, I saw the old man again recently, when I was going out to dinner in the city where he lives. There he was, walking down the sidewalk with his wife, right past where I had just parked my car. He was wearing a sweatshirt with the name of his university employer on it. I'd never seen him out of a suit before. I thought he seemed older, frumpier, humbled. Or perhaps that was just my wishful thinking?

A lot has happened since the last time I saw him. He was no longer the department chair, replaced by someone known for work related to ethics. I briefly considered going up to him and saying something, but what? "Thank you for being an example of what not to aspire to?" Or, "That's a very plain-looking sweatshirt; did all your industry funding dry up?" Poor sportsmanship and too passive-aggressive. I briefly imagined following him down the sidewalk, yelling: "Shame, shame, shame!"  But he probably would've mistaken me for a Scientologist or something.

Saturday, July 11, 2015

A Child Psychiatrist's Review of Pixar's Inside Out

I finally watched Disney/Pixar's Inside Out, and I agree with the consensus opinion that Pixar has done it again, making a movie that's both fun and poignant, with a narrative that young children can understand while containing deeper messages for adults. Read on for more of my thoughts, but be aware that MAJOR SPOILERS FOLLOW, since it is hard to discuss my thoughts as a child psychiatrist on the movie's depiction of emotions without going into the details.

Fear, Disgust, Joy, Anger, and Sadness.
The main characters: Fear, Disgust, Joy, Anger, and (sigh) Sadness.

The plot of Inside Out is fairly straightforward: a preteen girl named Riley moves with her parents from Minnesota to San Francisco, and she experiences a crisis in her emotional state, in her relationship with her parents, and in her concept of herself. Most of the action takes place inside Riley's head, where 5 different emotions (Joy, Sadness, Anger, Disgust, and Fear) take turns at the control center of the brain's headquarters, directing Riley's actions depending on which emotion is at the controls. Joy is the energetic (cheer)leader who attempts to remain in control as much as possible, especially over Sadness. The crux of the movie is about Joy going on a journey in which she (and everyone else) learns to value Sadness.

How the Pixar filmmakers takes us on the journey, though, is where they show off their delightful imagination and remarkably decent grasp of psychology. Here are my thoughts on the aspects of Inside Out that delighted me the most:
  • The movie demonstrates the inner workings of memory in a visually coherent and fairly accurate way. I especially like how Riley's incoming memories, which look like softball-sized glowing orbs, are temporarily kept at headquarters until Riley sleeps, at which point they are sent into long term memory. They also find a way to neatly show core aspects of Riley's identity/personality as floating islands that serve as repositories of concepts such as Family, Honesty, and Goofiness.
  • The depiction of the weight of parental expectations is very well-done. When Riley becomes upset after the move, her parents say to her: "Where's my happy girl?", clearly indicating their preference for how she should feel. This is one way that parents insidiously and inadvertently tell their children it's not OK to be sad, and the fact that (if I recall correctly) each parent says this to Riley on separate occasions shows that Pixar is emphasizing the harm that this sort of communication can do.
  • A critical scene that works incredibly well both as a turning point in the plot and a learning opportunity is when Sadness convinces a character to do something that Joy could not, simply by listening and showing empathy for that character's feelings. This teaches Joy (and us) the importance of validating another person's emotions.
  • Some of my favorite moments in the movie are when it delves into the minds of characters other than Riley. I really enjoyed how each character has a different predominant emotion, and the emotions work together in different ways depending on the individual. For example, inside the head of Riley's mother, the different emotions sit around like a committee with Sadness presiding, while a teen boy's mind is dominated by fear, with all his emotions running amok.
  • When Riley and her father get into an argument during dinner, the camera dives into each person's mind and clearly shows how Anger in one person leads to escalating Anger in the other, in a mutually assured destruction kind of way. This is a good example of an amygdala hijack, which comes up frequently when I discuss family conflict with patients.
  • Despite being a primary emotion, each of the emotion characters are capable of expressing other emotions. This helps make them more interesting and less one-dimensional; it also helps subtly reinforce the point that having one emotion dominate all the time may not be desirable.
  • Initially, each of Riley's memories passing through the control center is a distinct color, corresponding to the emotion associated with the memory. By the end of the movie, memories have become multi-hued, nicely illustrating Riley reaching a developmental stage where she is capable of more emotional nuance.
However, I do have one major criticism, and that is the portrayal of Sadness as short, rotund, and bespectacled. How…sad that Pixar uses such obvious stereotypes to depict her appearance! Sure, this may get more laughs from the audience and fit the look of the actress supplying the voice, and the movie does try to redeem itself by turning Sadness into a heroine. But how would kids fitting that description feel inside early on, even if they're laughing along with everyone else on the outside? I wish Pixar had simply portrayed Sadness on the basis of her facial expressions and body language without adhering to our cultural norms regarding the physical characteristics of a sad person; they're good enough animators to be capable of that. A few of other nitpicks:
  • A scary clown is locked away in Riley's subconscious, visually depicted as a vault in a deep cavern. I'm not sure if even the psychoanalysts still use the term "subconscious," yet it persists in the popular culture, perhaps because it's so easy to conjure up that visual image of something deeply buried.
  • Memories, of course, are not accurate recordings preserved in amber, but are malleable and often unreliable. While it would have been nice for the movie to show this, I understand that it would probably overcomplicate things. Similarly, expanding beyond just the 5 emotions featured would have been nice but too complicated.
  • Though dramatic, I do not feel that the scene of Riley taking a credit card from her mother's wallet and getting on a bus back to Minnesota is very believable. Given her generally good relationship with her parents in the past, it would take much more than a couple of arguments to make a kid who did not have previous conduct problems steal and run away from home.
Despite my criticisms, Inside Out is easily one of my three favorite Pixar movies of all time, along with Wall-E and Ratatouille. I can even envision it being useful in therapy. Asking a child to think about a situation and consider what Joy would say versus what Sadness or Fear would say about it might help make cognitive-behavior therapy more engaging and fun. If you're a child therapist/psychologist/psychiatrist and haven't seen it yet, what are you waiting for? It's the only Pixar movie where I'm eagerly anticipating a sequel, given the portents at the end about Riley turning 12. I'd love to see what Pixar does with the even more tangled emotions and relationships of adolescence.

Tuesday, May 19, 2015

Free Branding Advice For The American Psychiatric Association

On Sunday, while going about my weekend business (which means possibly wasting some time on Twitter), I was greeted with this unsolicited gift from the American Psychiatric Association:
There's also an announcement on the APA website and an accompanying Youtube video. Here's an alternative version of the new logo:

American Psychiatric Association Logo w/ Brain

Now, I'm not an APA member, but as a psychiatrist, this is just embarrassing. Poor Benjamin Rush must be rolling over in his grave! I'm also not a "branding expert," but it seems that the APA could use all the help it can get these days. Thus, I'm offering some pro bono advice as a public service.


First off, the text becomes very fashion-forward with the use of a skinny font (resembles Avenir, but I'm not sure exactly what it is) for "American" and "Association." The semi-bold and colored emphasis on the word "Psychiatric" just seems a bit…desperate. Look at us, we're psychiatrists! I'm not saying that the typeface doesn't look nice, but it smacks of trying too hard to match the latest trends in visual marketing:

Apple Watch Edition

Now, Apple can do with this because they actually are producing new high-tech products. But the APA? Sorry, I don't think Understanding Mental Disorders: Your Guide to DSM-5 qualifies. Why not make something that looks timeless and classy, rather than trendy and fashionable? Here's my suggestion:

American Psychiatric Association Classier Type

This has the added benefit of allowing the letters "APA" to line up, emphasizing to the world that the fight over what "APA" stands for is not over, even though the American Psychological Association owns and the Google search results. We psychiatrists don't give up!


Though I discussed the choice of typeface first, the new logo emphasizing the brain is the most jarring aspect of the APA brand refresh. Here were my initial thoughts:
A couple of days later, I still feel the same way. If you're trying so hard to signal that the organization is modern and future-looking, then why in the world use such a literal outline of a brain? The whole point of logos is to make a simplified visual representation of something so it becomes an instantly recognizable icon. That's why Apple's logo doesn't look like an actual silhouette of an apple, and the Microsoft Windows logo doesn't look like a photorealistic window. It's also why the serpent on the Rod of Asclepius winding its way through the brain (wisely) does not show snake scales. Also, note what happens to the APA's brain when it's shrunk:

Fuzzy APA Brain Logo

Look how fuzzy the brain becomes, while the Rod of Asclepius retains its shape nicely. So, APA, if you're going to use a brain with folds, then at least make them look somewhat rounded:

Rounded APA Brain Logo

Even though it's a bit cartoony and not anatomically accurate, it's at least visually cogent, especially at smaller sizes. Alternatively, you can get even more minimalistic:

Smooth APA Brain Logo

These changes took me all of 20 minutes in Photoshop, and I'm no graphic artist. I wonder how much the APA paid their consultants for all this?


Finally, that tagline: "Medical leadership for mind, brain and body." While I won't argue too much over the missing Oxford comma, I do think: wouldn't it be nice if the tagline matched the typeface and the logo? The typeface signals future-think, while the logo features a traditional symbol of medicine within the brain. I don't see anything conveying "mind" or "body." Since I believe honesty is the best policy when it comes to branding, why not this:

APA: Leaders in medicalizing the brain.

Or even better, if the focus in going to be on medical brain disorders, why not a complete rebrand of the APA into something even awesomer?

American Clinical Neuroscience Association: Leaders in medicalizing the brain.

There, that's more like it!