Friday, October 31, 2008

You Really Can Report Safety Data

A new study concluded that the combination of sertraline (Zoloft) and cognitive-behavioral therapy (CBT) worked better than either treatment alone for children with anxiety disorders. There was even a nonsignificant trend for Zoloft to outperform CBT, which was quite surprising to me. But that's not really the point of this post. The study can be read at the New England Journal of Medicine website.

I'd like to commend the researchers on doing something that is exceedingly rare in psychopharmacology and psychotherapy trials -- they gave a detailed report of adverse events. And we find that a greater percentage of kids showed suicidal ideation on... CBT. It was not a statistically significant difference, but it was nonetheless surprising. Zoloft, however, was related to significantly more disinhibition, irritability, restlessness, and poor concentration than CBT. This may have been a fluke, but two participants on Zoloft had "homicidal ideation" compared to none on CBT. I have bitched several times about missing/mysterious data on adverse events in psychiatric drug trials, and some have also complained that psychotherapy trials do a poor job of tabulating adverse event data. Again, kudos to the study authors for reporting adverse events; imagine if reporting safety data in such a manner was commonly practiced.

Source: J. T. Walkup, A. M. Albano, J. Piacentini, B. Birmaher, S. N. Compton, J. T. Sherrill, G. S. Ginsburg, M. A. Rynn, J. McCracken, B. Waslick, S. Iyengar, J. S. March, P. C. Kendall (2008). Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety New England Journal of Medicine DOI: 10.1056/NEJMoa0804633

Monday, October 27, 2008

Psychiatric Diagnoses: Fact or Fiction?

Below is a guest post from Tim Desmond. I do not necessarily agree with all of the the contents of the post below, but I thought the topic was thought-provoking and controversial, so I have agreed to publish it. Feel free to add comments as you see fit; I will likely add my two cents in the next couple days...

I would like to contribute to the discussion on this blog by summarizing the work of Richard Bentall, psychologist and award-winning author, on psychiatric diagnosis and the DSM-IV. While we may be able to agree that long-term use of neuroleptics should not be the treatment of choice for schizophrenia, or that bipolar disorder is being over-diagnosed in children, I would invite us to question whether 'schizophrenia' or 'bipolar disorder' are valid diagnoses at all. Over the course of his career Richard Bentall has critiqued the medical model of modern psychiatric diagnosis and proposed instead a more personalized symptom-based approach.

The basic question is this: Do people suffer from a finite number of discrete psychiatric disorders/diseases or do people experience varying degrees of human suffering in their own idiosyncratic ways (which include spectrums of sadness, fear, dissociation, etc)? The modern mental health establishment clearly subscribes to the former as evidenced by the structure of the DSM and the theory of 'chemical imbalance.' This belief is so pervasive that even people who claim to disagree with the medical model of diagnosis often think within its terms. For example, the idea that one can be 'misdiagnosed' presupposes that a correct diagnosis could exist. Similarly, saying that schizophrenia is partially caused by psychological factors assumes that 'schizophrenia' is a valid way to group people.

The theory that psychological distress is caused by a finite number of psychiatric diseases can be attributed to Emil Kraepelin, who first published his Compendium of Psychiatry in 1883. Kraepelin believed that the psychiatric patients he treated suffered from diseases analogous to any treated by a practitioner of internal medicine. (Note the common comparison today between psychiatric diagnoses and diabetes forwarded by the pharmaceutical industry.) He said a specific disease process should generate identical symptoms, have identical pathological anatomy and identical etiology (or cause). According to Kraepelin, all that was needed was for these diseases to be discovered in order for diagnosis and treatment in psychiatry to catch up with the rest of medicine. Since it was far beyond the knowledge of his time (or ours for that matter) to find common pathological anatomies or etiologies, he chose to group symptoms. He believed that if he grouped symptoms 'correctly' the people grouped together would be sharing the same underlying disease. They would therefore have the same anatomical problems, the same etiology and respond more or less identically to treatment. He hoped that this kind of systematizing would lead to great advances in the efficacy of treatment.

While Kraepelin's categories have changed over time and grown from 3 to over 200, the basic idea persists to this day – that there are a finite number of discrete psychiatric disorders/diseases people can have and if we were to somehow group symptoms 'correctly' we would have isolated real disorders/diseases.

The problem with this idea is that it is not at all based in evidence. It began as Kraepelin's assumption and he was unable to provide any research in his lifetime to support it. However, it has been an idea so compelling to psychiatrists that they have tried in vain to support it for over one hundred years. In fact, there is a large body of research that directly contradicts this theory.

For example, you would expect that if one doctor diagnosed you with Strep Throat, you would be able to go to any other doctor and get the same diagnosis – and you'd be right. The reason for this is that Strep Throat is a real disease associated with an infection of streptococcal bacteria. You either have it or you don't and there are reliable ways to test if you do.

However, if you are experiencing severe psychological distress and one psychiatrist diagnoses you with "bipolar disorder" there is only a 50-60% chance that the next one you see would give you the same diagnosis. Why is this? Both psychiatrists would have been highly trained in diagnosis, and they would be using the same criteria to make their judgment. So if one says you have PTSD, another says bipolar and a third says brief psychotic disorder, which is the "correct diagnosis?" What do you really have?

Bentall argues the problem is that Kraepelin's main assumption – that there are a finite number of discrete psychiatric disorders – is just not true. You don't have any of those disorders because they are not real. Instead he argues that any psychiatric patient is experiencing a high level of emotional distress that is expressing itself through a range of symptoms and these symptoms can be better understood as extreme expressions of normal human responses to distress.

Bentall advocates for abandoning psychiatric diagnoses altogether. He claims that psychiatry's stubborn attempt to treat mental distress as a medical problem is what has led to its inability to improve treatment outcomes over time. Citing a large body of research, Bentall shows that symptoms from depressed mood to hallucinations can be accounted for psychologically and that doing so is not only more in line with science but more humanizing to patients. Therefore he favors what he calls a 'complaint-oriented' approach in which each patient would be assessed according to his or her unique symptomology. The focus becomes the symptoms themselves and we avoid trying to groups them into arbitrary non-existent disorders. Symptoms can be understood and treated, while disorders cannot because they are not real.

To learn more about Bentall's work, read his 'Madness Explained' which won the British Psychological Society's Book Award.

Author Note: Tim Desmond offers phone counseling and training for therapists through his website at

Saturday, October 18, 2008

The Latest on Kiddie Bipolar

A recent study in the Archives of General Psychiatry claimed that kiddie bipolar tends to become adult bipolar. I have read the study and have a few comments. First, the authors' main findings:
  • Children diagnosed with bipolar went on to have a manic episode 44% of the time.
Let's look at the study sample. Seven to 16 year olds who were experiencing a manic or mixed episode. At 8-year follow up, 54 kids had reached at least age 18. So we're talking about 24 of 54 kids who went on to experience a manic episode as adults. Not exactly a huge sample. As time moves along, there will likely be more kids from this study who experience manic episodes as adults, so it is very much possible that when all 115 kids originally enrolled in this study hit, say, age 30, more than half of them will have experienced a manic episode as adults.

The argument then goes that we must treat child bipolar early and intensely in order to prevent these kids from going on to develop bipolar disorder as adults. So, were these kids receiving treatment? Definitely. These kids received whatever treatment was offered in the community, which doubtlessly included stimulants, mood stabilizers, antidepressants, and antipsychotics. On many occasions, they were probably undergoing some serious polypharmacy driven out of desperation rather than any sort of reasonable evidence base.

So did the treatments work? 88% of people who had an original manic or mixed episode recovered, but 73% of these kids then had a relapse afterward. And if nearly half went on to experience mania as adults, doesn't that mean that treatment was not exactly working very well? At this point, the authors have not reported what treatments were used, but I am willing to bet that the polypharmacy I mentioned above was often in place and that very few of these kiddos weren't receiving regular psychopharmaceutical treatment.

Bipolar was not the only problem facing these kids. 94% had an ADHD diagnosis at some point during the 8-year followup and a similar number had some sort of disruptive behavior disorder diagnosis. So it's not just bipolar. As I've been saying for a while now, bipolar is just the name du jour for kids whose behavior is really, really bad. We used to call it ADHD or conduct disorder and now it's ADHD, conduct disorder, and bipolar disorder just abbreviated as "bipolar," driven by the market reality that there are quite profitable drugs used to oh-so-successfully treat kiddie bipolar. But it seems they can't be working that well if 73% of these kids who recover from an episode end up relapsing.

I would love to write more about how bipolar was diagnosed in these kids, but I've not been able to land a copy of the measure used to make bipolar diagnoses in the study. The authors state that they only counted episodes that met DSM-IV criteria; if I ever find time, I might look at this more closely.

And note that we don't know what happened to the youngest kids in the study (those who started at ages 7 or 8) because none of them were adults at the end of this study. This study did not include anyone younger than 7, so the rash of 4 year olds being diagnosed as bipolar is left unexamined.

Bottom Line: Assuming that the diagnoses were valid, this study makes me think that:
  • Kids who show really bad behavioral and emotional problems often become adults with major psychological problems. Not exactly earth-shatteringly surprising.
  • Treatments for child/adolescent bipolar are not working very well.

Furious Seasons also has a number of concerns about the study.

Friday, October 10, 2008

APA Membership Rejects Torture

APA Membership Rejects Torture

The American Psychological Association membership recently overrode their leadership (the Council of Representatives) via member vote. After significant grassroots organization by several psychologist organizations, the APA was forced to send out a ballot asking members whether APA members should be allowed to work in settings where detainees were held in inhumane conditions and/or in sites that operate outside of the Geneva Convention. And over 60% of respondents said no to psychologists working in settings where inhumane treatment occurs unless it is in the service of detainees, treatment to military members, or a human rights organization.

Then APA President Alan Kazdin issued a letter to President Bush. The full text is available here. Here's one particularly relevant excerpt:

So now APA has finally caught up with the American Psychiatric Association and the American Medical Association, who have banned their members from participating in such activities for years. Not all psychologists are members of APA, so APA does not have any jurisdiction over their behavior. Additionally, passing a change in policy does not physically stop some individuals, in the name of sadism, peer pressure, or defense of country, from abetting or engaging in torture. Nonetheless, on at least a symbolic level, it's nice to see that the membership of APA stood behind this issue.

Let me clearly mention that I have nothing against psychologists in the military, as the mental health needs of the military and their families is a highly important issue. Another important principle: Do No Harm, including to so-called enemy combatants or whomever else was receiving "enhanced interrogation" from psychologists and others.

APA, of course, has always been against torture in principle, but the position they took against it was a little watered-down for my taste, so I'm glad to see that their stance has, by force of the membership, become more clearly anti-torture. An interesting piece from one of the most prominent advocates of altering APA policy on this matter can be read here. The disgusting work products of some psychologists who actively engaged in torturous practices are described in a rather shocking Vanity Fair article.

And please, oh please, let nobody take the tack that I am some left-wing pro-terrorist nutjob just because I believe that torturing the hell out of people is both unethical and ineffective.

Monday, October 06, 2008

A Month in The Life of Chuck "High Life" Nemeroff

The psychiatry world is belatedly exhibiting outrage toward a man whose ability to lure pharma cash seems to know no bounds. He may be the textbook case of a key opinion leader. Of course, I speak of Charles "Bling Bling" Nemeroff. Rather than list the many questionable at best behaviors he has exhibited, each of which has called into question his standing as a scientist as opposed to a blatant drug marketer, I just want to a) direct everyone to a detailed list of his speaking engagements from GlaxoSmithKline and b) discuss a month of living the High Life, Nemeroff Style.

As is well known by now (1, 2), Nemeroff appears to have not been particularly forthcoming about the huge amounts he was making while moonlighting for every drug company on the planet (see below) despite requirements that he do so. According to psychiatrist Danny Carlat:
From 2000 to 2006, GSK paid Nemeroff a total of $960,488. Note that this was not research grant money, or money for Emory's psychiatry department. These were fees that went into his personal bank account, which he earned by either sitting on GSK's Advisory Board, or speaking to doctors about GSK products. His typical fee for a talk was $3500 plus expenses, but sometimes he made more.

Of this $960,488, the total amount he disclosed to Emory [his employer, to whom he was required to report such income] was $34,998.
According to a GSK document hosted by Senator Charles Grassley, Nemeroff took in over $20 grand in one month from speaking engagements for GSK. Not bad work if you can get it, eh? And this month doesn't seem unusual for Nemeroff. These are only his speeches for GSK -- he also gave speeches for several other companies. The document goes on and on -- 39 pages of paid speech listings, nearly all of them featuring Nemeroff. I just picked 03-30-00 to 04-30-00 because they were on the first pages of the document, which covers expenses from 2000 to 2008 for Dr. Bling Bling.

Nemeroff GSK Honoraria from March 30, 2000 to April 30, 2000
Speaking Fee
$4175 (includes some 'expenses'; I suspect $4000 was the speaking fee)
$21, 175 (probably $21,000 excluding travel expenses)

Imagine making $20k in a month for basically reading slides a few times that were quite possibly entirely written by a drug company. And many of these talks were accompanied by posh meals, the kind that myself and most of my readers might eat once or twice a year.

Here's a Nemeroff disclosure from a recent journal article:

Dr Nemeroff has received grants from or performed research for the American Foundation for Suicide Prevention, AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, Inc, Janssen Pharmaceutica, NARSAD: TheMental Health Research Association, the National Institute of Mental Health, Pfizer Pharmaceuticals, and Wyeth-Ayerst Laboratories; has been a consultant to Abbott Laboratories, Acadia Pharmaceuticals, Bristol-Myers Squibb, Corcept Therapeutics, Cypress Bioscience, Cyberonics, Eli Lilly and Co, Entrepreneur’s Fund, Forest Laboratories, Inc, GlaxoSmithKline, i3 DLN, Janssen Pharmaceutica, Lundbeck, Otsuka America Pharmaceutical, Inc, Pfizer Pharmaceuticals, Quintiles Transnational, UCB Pharma, and Wyeth-Ayerst Laboratories; has been on the speakers bureau for Abbott Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Pharmaceuticals; is a stockholder in Acadia Pharmaceuticals, Corcept Therapeutics, Cypress Bioscience, and NovaDel Pharma Inc; is on the board of directors of the American Foundation for Suicide Prevention, the American Psychiatric Institute for Research and Education, the George West Mental Health Foundation, NovaDel Pharma Inc, and the National Foundation for Mental Health; holds patents on a method and devices for transdermal delivery of lithium (US 6,375,990 B1) and on a method to estimate serotonin and norepinephrine transporter occupancy after drug treatment using patient or animal serum (provisional filing April 2001); and holds equity in Reevax, BMC-JR LLC, and CeNeRx.
No, I didn't make that up. As Ed Silverman wrote at Pharmalot, "It also raises a question - when he did find time to do anything else?"

Friday, October 03, 2008

Uh-Oh Chuck, They Out To Get You, Man

According to the New York Times and Wall Street Journal, it looks like Charlie "Bling Bling" Nemeroff is under investigation by Senator Charles Grassley. Gee, I can't imagine why. Maybe because documents indicated that he failed to report over a million dollars of income received from the drug industry? It also turns out that the Chuckster made nearly $3 million in consulting deals with pharma from 2000-2007. That doesn't mean that his behavior was ever influenced by such huge sums of cash, right? Oh, wait just a minute...

...It turns out that there were several incidences of unbecoming behavior involving Bling Bling, I mean, the esteemed Dr. Nemeroff. Who could forget the time that he conveyed what appears to be fictional data in a continuing medical education course? How 'bout an article that seems to overstate the advantages of Effexor (1, 2)? And his contradictory statements regarding the role of serotonin in depression? His involvement in a shady at best study on the effects of Risperdal in depression is also worth reading. In fact, for a summary of many issues regarding Nemeroff, feel free to read an earlier post that outlines many events and provides links for more in-depth information on each of them.

One of my first posts on Nemeroff was presciently titled: Uh-oh Chuck, They Out to Get Us, Man. Apparently, I was foreshadowing the present investigation. Don't feel too bad for Nemeroff; he should be able to afford excellent legal representation.

Maybe this latest mire in which Nemeroff finds himself explains the uptick in hits from Emory University and the Senate this site has been seeing lately?

Please also read Daniel Carlat's unflattering take on Nemeroff's behavior.

Wednesday, October 01, 2008

Prialt Pushed Through Duplicate Publication

Apparently, the same data on Elan's pain medication Prialt (ziconotide) was published twice. Same data set. No reference in the second publication to the first publication. As I noted last week in a post about Cymbalta, that's not supposed to happen. It's the sort of thing that leads physicians to believe that a medication has a lot of supporting evidence -- "Of course I prescribe it; I've seen two positive clinical trials" -- when in fact it's just the same data being repackaged in another journal. The full story is contained in two posts at The MacGuffin (1, 2). An infomercial passing off as continuing medical education is also involved in the plot. Count The MacGuffin as an official must-read blog.