Pseudoscience, Candy, and Lamar Odom: Brought to you by Daniel Amen

If you follow professional basketball, you've probably noticed that LA Lakers forward Lamar Odom has a well-deserved reputation for inconsistent play. When he's good, he's close to amazing, and when he's bad, he's of little use to his team. So how is this related to mental health? Does he have social anxiety disorder? No, get out of Ricky Williams mode and pay attention...

Odom eats candy. Lots of it. And that's why his play is inconsistent. At least that's the story according to Dr. Daniel Amen, who, according to the Los Angeles Times stated:

Odom freely confesses that he just can't help himself when it comes to the sweet stuff and always keeps a stash on hand of Gummi Bears, Honey Buns, Lifesavers, Hershey's white chocolate, Snickers bars, cookies and more. He eats the sugary snacks morning, noon and night, and even says he sometimes wakes up in the middle of the night, chows down on some treats, then falls back asleep.

This is bad news for the Lakers. I've been telling my patients for years that sugar acts like a drug in the brain. It causes blood sugar levels to spike and then crash, leaving you feeling tired, irritable, foggy and stupid. Eating too much sugar impairs cognitive function, which may explain why Odom doesn't always make the smartest decisions on the court. . . .

As a fan and a physician, it concerns me that our professional sports organizations and players are not more concerned about brain health, which includes nutrition. My advice to Odom and to all sugar addicts is to get your sugar consumption under control. You'll feel so much better and your brain will function better too. And, maybe the Lakers can get their 15th championship and Odom can get his first.

Now, remember that Odom's play is inconsistent, not consistently bad. And if he is eating sugar all the time, shouldn't his play be consistently poor? Oh, and is there any science at all to support the idea that eating sugar impairs athletic performance...? I'll admit to not being a top expert on this, but my brief search of PubMed did not bring up anything to support Dr. Amen's suggestions.

So who is this Amen guy, anyway? He claims that Alzheimer's can be detected early through the use of SPECT brain imaging (single photon emission computed tomography). And he sells vitamins/nutraceuticals on his site which, of course allegedly help to prevent cognitive deterioration. There is sooooooooo much more to read about Amen, and I encourage y'all to head over to Salon to read an excellent debunking of Amen's many pseudoscientific claims.

I've rolled my eyes at this guy for years, but now that he's trying to shoot his witchcraft at the fine sport of basketball, I've hit my breaking point. But what do I know... I mean, Amen apparently wrote that

From the first month that I started to order these (SPECT) scans, I felt that they had a special place in science and that I was led by God to pursue this work

And who am I to argue with a guy who was sent by God to practice medicine. But back to Lamar Odom; he insists that he ate candy for breakfast on the game days in which he played well against the Denver Nuggets. Well, maybe, but I bet a SPECT scan or two would figure out why his performance is inconsistent.

Dr. Amen also has some hot, hot science about the men, sex, and the brain. On The View, of all places. Get ready to cringe.



OK, fine. One more. Dr. Amen can target treatment for ADHD appropriately by... yes, using pricey and unproven brain scans! See below...

Clinical Trial Registry of WHAT?

Worried about data being hidden in clinical trials, with negative data regarding a drug's safety and/or efficacy being buried? Worry no longer. At least that's what the super-optimistic authors in the New England Journal of Medicine would have us believe. Here's what they wrote:

Of special interest to us, an additional provision of the act requires sponsors of all clinically directive therapeutic trials to register their studies, at inception, in a public database sponsored by the National Library of Medicine. Although some aspects of this provision are not ideal, such as the delayed public availability of registration information on device trials and the noninclusion of phase 1 trials, mandatory registration represents a critical advance in making clinical trials of new treatments public knowledge.

AND

A decade ago a clinical trial could be conducted in secret. The trial’s sponsor, claiming proprietary rights, could keep all information about it, including its very existence, private. Thus, if a drug had important adverse effects, this information might never be made public. Legislators believed that such a possibility was not in the best interests of the American people. Once a clinical trial is mounted, the sponsor has an ethical obligation to publicly acknowledge the contribution of the participants and the risk they have taken by ensuring that information about the conduct of the trial and its principal results are in the public domain. With the FDA Revitalization Act, the United States joins other countries in recognizing that the human volunteers needed to complete a trial are more precious than the money required to mount it.

Wow, everything is looking up now! All data will be reported and all will be well. I read what I think is a relatively updated version of said legislation, and I did not really see anything that requires that all results are reported for every trial. Nothing even close to that is described, unless I missed something. Data reporting requirements should be pretty simple: Data on every single efficacy and safety measure must be reported in full. Nothing less is acceptable. Otherwise, sponsors can continue to fund research from which the positive data are reported and the negative data are minimized.

The Present System is Broken. Here's an example of why the present Clinical Trials database is close to useless for learning about study results. First come snippets from a registered clinical trial, then comes the publication based upon the results. Snippets from trial protocol (what was going to happen in the study):

This is a study of the effectiveness of adding Abilify (aripiprazole), an atypical antipsychotic medication, to ongoing SSRI antidepressant treatment for depressed outpatients who are not responding fully to SSRI treatment alone. It is hypothesized that patients’ functioning will improve after 12 weeks of treatment with Aripiprazole and SSRI medication...

Total Enrollment: 15...

Primary Outcome Measures:

• Hamilton Depression Rating Scale (HDRS)

Secondary Outcome Measures:

• Clinical Global Impressions Scale (CGI)
• Global Assessment of Functioning Scale (GAFS)
• Beck Depression Inventory (BDI)

Study chairs or principal investigators

David J. Hellerstein, MD, Principal Investigator, NY State Psychiatric Institute, and St. Luke's - Roosevelt Hospital Center

Publications
Hellerstein DJ. Aripiprazole as an adjunctive treatment for refractory major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Dec;28(8):1347-8. No abstract available.

Clinical Trial Entry vs. The Publication. You can see the details above. 15 patients to be enrolled in the study using four measures of outcome. Let's see what that cited publication had to say about the results...

Ms. V. is a 46-year-old single female with a 5-year history of severe depression... What about the 14 other patients?

At that point [venlafaxine + mirtazapine not working], aripiprazole was added, initially at 15 mg/day then increased to 30 mg/day. Within a month, Ms. V. noted that her mood and concentration were improved, and she was no longer anhedonic. She began socializing with family members again, began gardening and was able to concentrate on reading and movies. After 3 months on the venlafaxine extended-release, mirtazapine, and aripiprazole, Ms. V. noted that her appetite remained good, she was sleeping 7 h per night, her mood was much better, and she had begun to seek a new job, sending resumes and phoning prospective employers... What happened to those measures of outcome mentioned above?

The linked publication discusses one case though the trial was to study 15 people. Did the other 14 all jump off a bridge? What happened? If we are going to have a clinical trial registry that requires reporting of results, is this what you want? I hope not. Next, the obligatory pro-Abilify propaganda, such as...

Furthermore, aripiprazole’s benign side effect profile [including minimal weight gain, sedation and parkinsonism, resulting from its low affinity for alpha-1-adrenergic, histamine (H1) and muscarinic (M1) receptors] suggests that it may be tolerable for refractory-depressed patients, who may need adjunctive treatment for a long period of time. The case of Ms. V. suggests the possible benefit of aripiprazole in treatment-resistant depression as an adjunct to other antidepressant medications.

When there is no clinical trial data to support your discussion, one can always fall back on discussing various receptors and how, theoretically, tweaking them in one way or another is going to lead to positive results.

The case study ends with:

Further studies of aripiprazole as an adjunctive medication for treatment-resistant depression are indicated.

Yeah, but what happened to the 14 other patients in this study?? I did a search on Medline to find if there were additional studies by Hellerstein using Abilify in depression and I could find nothing that seemed to fit the bill. Please alert me if I missed something in the search. One could argue that perhaps the study is in the midst of being written up for publication -- if so, it's sure taking a while...


There's More. If I had more time, I'd go through the clinicaltrials.gov registry and I'm sure I'd find more interesting discrepancies between clinical trial protocols (where researchers say what is going to happen) and what was actually published (the official record of what actually happened). In fact, I've done this before, in which I noted that a published study of Risperdal for depression was clearly changed in its data reporting somewhere between the clinical trial registry and the eventual publication. A rather thorough investigation into the topic found that:

"Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary."

Who Cares? Well, if you don't mind receiving only part of the efficacy and safety data, then don't do anything. Send no emails, tell none of your friends, don't bother your local journal editor, and don't ask your doctor if he/she is aware that the so-called bedrock of evidence based medicine (i.e., results published in scientific journals) is based on selectively reported information.

The Kool-Aid. I'm really stunned that the folks at the New England Journal of Medicine would just rush off and publish an essay about how great things are now going to be. People have been calling out for data to be shared openly for quite some time, and now, magically, with the passing of some vague legislation, all data will be made publicly available. The drug industry is suddenly just going to publish all information on all of their clinical trials, overnight? And some bigwigs at NEJM are willing to drink this Kool-Aid? That is pathetic.

Peer Review, SSRIs, Suicide, and Booze

The recent study in the American Journal of Psychiatry by Gibbons, Mann, and colleagues regarding the relationship between SSRI usage and suicides reads more like an exercise for undergraduate students to find obvious errors than it does a real peer-reviewed study. Sounds mean, but keep reading.

The abstract of the study includes the following...

"In both the Unites States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents."

So less SSRIs = more suicides, according to the authors. Let’s see if this study actually shows such a relationship…

Look closely at the above graphs (click to enlarge) from the article. Note that the decrease in SSRI prescriptions from 2003 to 2004 was very slight across the 0-10, 11-14, and 15-19 age groups, which is the timeframe in which suicide rates for those aged 5-19 increased notably. The larger declines in SSRI prescribing for youth occurred from 2004-2005, which happens to be when the suicide rate for those aged 15-24 appears to have decreased from 10.3 per 100,000 (see Table 9; page 28 here) to 9.8 per 100,000 (see Table 7 here). Yes, I know I am comparing data for ages 15-24 to data on ages 5-19, but I think this makes sense when one considers that the suicide rate for those 14 and under is much lower than for those aged 15-24. Actually, grouping suicide data for ages 5-19 makes little sense to me given the vast differences in suicide rate within this age group.

It is important to note that the authors of the paper did not have data from 2005, but there is nothing from the 2003-2004 U.S. SSRI prescription data cited in their paper that even suggests a relationship between decreased SSRI use in youth and an increased suicide rate, as the decrease in prescriptions was minimal. Pay close attention: The authors ran a total of zero statistical analyses to examine the relationship between SSRI prescription rates and suicide rates in the United States. That’s right, zero. So they put up a couple of figures without a single shred of statistical evidence, then claim that declining SSRI prescriptions are associated with an increase in suicide rates. Any peer reviewer who was not drunk or on a high dose of Seroquel should have noticed this gigantic flaw.

In the discussion, the authors state: “While only a small decrease in the SSRI prescription rate for U.S. children and adolescents occurred from 2003 to 2004, the public health warnings may have left some of the most vulnerable youths untreated.” This is unadulterated speculation, which as I just mentioned is not supported by a single statistical analysis in their paper. It is also hard to imagine how an FDA warning in mid-October could make suicides earlier in the year increase. One can only wonder to what magical time-traveling extent an FDA warning in October could have increased suicide rates earlier in the year. This is so mind-bogglingly obvious that, again, the peer reviewers were possibly inebriated during the review process, or the editor published the paper over the objections of the reviewers. Am I being too nasty? I'm just trying to figure out how it got published and "good science" is not the answer.

The authors then proposed the following:

…we estimate that if SSRI prescriptions in the United States were decreased by 30% for all patients, there would be an increase of 5,517 suicides per year…

In addition…

In children 5 – 14 years of age, a 30% reduction in SSRI prescriptions would lead to an estimated increase of 81 suicides per year… Given that SSRI prescriptions for children under age 15 already underwent a reduction of approximately 17% from 2003 to 2005, we expect an increase of .11 suicides per 100,000 children in this age group. Since there are approximately 40 million children in this age group, we would expect 44 additional deaths by suicide in 2005 relative to 2003, or an increase of 18% in this age group.

Preliminary 2005 suicide data indicate a suicide rate in 5-14 year olds of .7 per 100,000, holding steady from 2004. This does not support the predictions of Gibbons and colleagues. Granted, the 2005 data are preliminary, but I’d be surprised if they showed a large change in the direction that Gibbons, Mann, and their team predicted.

Again, let me state that these are only correlational data and that data from clinical trials as well as other sources trumps these types of studies in any case. At the very least, when doing correlational research, try to control for covariates (other variables of interest), examine trends over a longer time period than one year, and maybe actually run some statistics. Oh, and avoid conclusions that require belief in time travel. There are even more potential problems, but the authors missed so many glaring basic issues that it makes no sense to go any deeper.

If data based on correlations is going to be trotted out to scare physicians into prescribing more SSRIs, then it should be examined whether the correlations provide even preliminary support for the idea that SSRIs might reduce suicide. I've criticized many studies on this site for a variety of concerns (like here and here, among many examples), and I think the present study is among the worst offenders of basic research methodology. Until we clean up the "science," don't expect much real progress in the mental health treatment world.

Background here and here.

Major Hat Tip: Furious Seasons.

Bias in Research: The Word is Spreading

Dr. John Grohol over at PsychCentral has issued an excellent post on bias in research. He aptly describes some of the many biases that enter into the research process and why we'd better be quite careful before we jump on the evidence based medicine bandwagon. A teaser follows, in which he discusses evidence based medicine:

It’s like buying a 14-chapter book expecting to get the entire story. But instead of getting the entire story, you find chapters 10-14 are missing, and that chapters 3-9 were written by an author that didn’t appear on the front cover of the book. But it’s not quite so obvious as that. Nobody tells you that chapters 3-9 were written by someone else, and nobody mentions that it’s actually a 14-chapter book that’s missing 5 chapters. It’s no wonder you come away from the book feeling a little confused and betrayed. It’s nothing like you expected or were promised.

Very well said! I salute his excellent post and refer all readers to check it out. For a somewhat similar and certainly windier take on bias in the research process, please read my earlier post.

Hat Tip: Furious Seasons

Pseudoevidence Based Medicine

An excellent (per usual) post on Health Care Renewal has some interesting quotes from an article (by Wally Smith) that discusses why all the talk about evidence based medicine is often nothing more than a smokescreen.

I think Wally would agree with the following statement: Physicians often believe that the medicines they prescribe have wonderful evidence of safety and efficacy, yet they frequently fail to consider the many biases in the research process that end up producing "evidence" that often resembles marketing much more than science. Background here and here (among many, many others).

I like the term pseudoevidence based medicine so much that I may have to use it intermittently with such terms as experimercial and evidence b(i)ased medicine.

While I'd like to quote extensively from Wally's piece, I'll send interested readers over to Health Care Renewal to check out the whole thing.