Monday, March 30, 2009

JAMA / COI / Robinson issue snowballs...

OK, this JAMA conflict-of-interest issue keeps snowballing.
End of last week, JAMA's parent organization, American Medical Association, called for a review of the issue:

http://online.wsj.com/article/SB123819137827260883.html

Apparently, this was in response to attention from a handful of places, including the
"Alliance for Human Research Protection,"
http://www.ahrp.org/

...as well as the fact the JAMA editor DeAngelis has been aggressively maintaining a couple odd views, such as: JAMA was totally caught off-guard by author Robinson's COI "revelation" published in BMJ; and also the idea that no one should be able to say anything on this whole ordeal until JAMA decides it has conducted its top-secret investigation.

As I have said: all it takes to determine whether Robert Robinson had some conflict of interest with Forest Labs, manufacturer of escitalopram, was to google the terms "Robert Robinson" and "Forest Labs."

When AMA looks closely at this specific study (PMID 18505948), they may have some more questions for DeAngelis about editorial review. Especially if AMA searches the web for all the comments on the critical design flaws in this study.

Get that CV ready, DeAngelis.

Friday, March 27, 2009

finally a brave psychologist: ""bending over backward" to play down negative implications"

Recent study:
http://www.msnbc.msn.com/id/29906327/
Headline:
"Debate over drugs for ADHD reignites; New data from study paints different picture than initial results from 1999."

Basically, currently, Pharma-sponsored psychiatrists are running all over the place pushing meds for a great range of problems that can be successfully managed with psychotherapy. There is little to no discussion of ever 'augmenting' with therapy, or giving a trial of therapy first, which seems reasonable in many cases, since talk therapy does not stunt growth, damage your liver, cause akathesia, or contribute to suicide.

The people to really counter this message should be counselors and therapists, through their professional organizations. But they don't. why not? DK. There are a few good hypotheses - I should blog up a good discussion of this soon.

But here in this news story, a psychologist finally gets off the two-handed nice-guy act (well, one one hand, the data show this, but on the other hand, blah blah blah let's all talk nice and respectfully this is science blah blah).

A psychologist lays it out there:
Why are we all bending over backwards to accept the twisted interpretations and explanations from these paid shills?

Monday, March 23, 2009

Recent news, on both the meds and therapy sides. Therapy wins. Meds wins the press release competition.

Two very significant stories about how to effectively treat depression just emerged. Therapy wins this one. Big time. Meds are left with mere speculation. Nonetheless, inspired by visions of huge Pharma paychecks, predictably, there were plenty of Pharma spokesmodels willing to get out in front of the media and declare how great meds are for treating depression.


On the therapy side, some great news: well-conducted cognitive therapy leads to impressive sustained benefit. These long-term outcome results have just been published in one of psychology's leading journals, "JCCP;" the Journal of Consulting and Clincal Psychology.

Vittengl, Jeffrey R.; Clark, Lee Anna; Jarrett, Robin B.
Continuation-phase cognitive therapy's effects on remission and recovery from depression. Journal of Consulting and Clinical Psychology. Vol 77(2), Apr 2009, 367-371.

http://psycnet.apa.org/journals/ccp/77/2/367/

For people diagnosed with major depressive disorder who successfully responded to cognitive therapy in the short term, maintenance of remission at 18 months was strong. The control group, with no continuing cognitive therapy but only assessment across time, did OK – actually did better than a lot of samples from long-term med trials.

This indicates, yet again, that cognitive therapy works for major depression, and indicates that treatment gains are maintained after discontinuation, and rates of remission can be sustained with continued treatment.

Side effects? Uh, like, they were not assessed since talk therapy does not lead to suicide, homicide, dry mouth, erectile dysfunction, jitteriness, or ringing in the ears (except for those familiar ringing echoes of your therapist’s voice).

But you did not hear about this in the news anywhere.

At the same time, yet another SSRI med, received approval for short-term efficacy for adolescents with depression. Great news – for Forest laboratories, and all of the docs getting favors for being compliant with big pharma’s promotion-therapy.

And this has received news coverage.

http://www.docguide.com/news/content.nsf/news/852571020057CCF68525757F0067B7C3

http://www.medicalnewstoday.com/articles/143167.php

http://news.yahoo.com/s/hsn/20090320/hl_hsn/lexaproapprovedforadolescentdepression

Et cetera.

Now, it might occur to you to ask whether escitalopram might work for the long term.

Well, somehow the FDA is able to discern this answer: press release info declares: “Although maintenance efficacy in adolescent patients has not been systematically evaluated, the FDA in its review concluded that maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.”

What?

And they can’t discern that a majority of the benefit from escitalopram is placebo effect?

I will have to get hold of this FDA info and look it over.

No worries in the meantime. The press release info notes that Escitalopram is “well tolerated.” If it is as well tolerated in adolescents as in adults, that is not a good thing. At some other time, I will pull out the escitalopram side effect data and I will blog on what “well-tolerated” means. Short story: suicide, aggression, and more.

Sunday, March 22, 2009

"Soldier Suicide Rates Continue to Rise" - Suspect SSRIs

JAMA has recently posted a sad story: very high suicide rate among gulf war soldiers and vets.

Why? no one really knows.

But I am surprised that one obvious theory has not been covered: SSRI-related suicide.

The DoD and the VA simply do not have enough mental health counselors to conduct adequate counseling for these guys.

To manage the burden of psych problems, however, nearly every guy is given an Rx for an SSRI.

Newsweek, and some other media, have noted this. Vets get SSRI, not psychotherapy.

For PTSD, decent psychotherapy is definitely better than SSRIs.

The only drug that really helps some dimension of PTSD is prazosin - ridiculously inexpensive, with very clear empirical evidence. Simply enter "prazosin" and "sleep" and "PTSD" into pubmed, and start reading until you are convinced.

In the meantime, other drugs may have some wishy-washy evidence, but look at placebo effect, study design, etc., and enthusiasm fades for the Med approach.

A big problem is that these guys may not be the ones to give SSRIs like candy.

Google "SSRI" and "Suicide," and start reading.

How is a drug that is supposed to make things better contributing to suicide?

Well, NIH, that would be a good study to fund.

Nitric Oxide is one of the brain's neurotransmitters.
Among its roles, it has a role to curb or restrain or control aggression: For example:
2007: Impaired Nitric Oxide Synthase Signaling Dissociates Social Investigation and Aggression "These data suggest that further study of nNOS signaling is warranted in mental disorders characterized by social withdrawal and increased aggression."
2001: Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase"These results indicate an important role for NO in normal brain 5-HT function and may have significant implications for the treatment of psychiatric disorders characterized by aggressiveness and impulsivity."


SSRIs interfere with nitric oxide:
Finkel MS, Laghrissi-Thode F, Pollock BG, Rong J. Paroxetine is a novel nitric oxide synthase inhibitor. Psychopharmacol Bull. 1996;32(4):653-8.


The interference from SSRIs on nitric oxide could be the mechanism for the noted problem of bleeding in SSRIs (cf: Shen WW, Swartz CM, Calhoun JW. Is inhibition of nitric oxide synthase a mechanism for SSRI-induced bleeding? Psychosomatics. 1999 May-Jun;40(3):268-9.).
SSRIs may also lead to erectile dysfunction through interference with nitric oxide (cf:Angulo J, Peiró C, Sanchez-Ferrer CF, Gabancho S, Cuevas P, Gupta S, Sáenz deTejada I. Differential effects of serotonin reuptake inhibitors on erectile responses,NO-production, and neuronal NO synthase expression in rat corpus cavernosumtissue. Br J Pharmacol. 2001 Nov;134(6):1190-4.).


So, what does all of this have to do with the soldiers?
We know that plenty of sodiers are getting SSRIs when they complain about any mood/affect type problems. Because of the baseline mental difficulties, these guys may be at heightened risk to the agressive effects of SSRIs. This may be leading to the killings and the suicides.


How to figure this out?
The VA has cadres of researchers, and the best integrated electronic medical record ever. Just get one of the researchers to design a study to look at Rx SSRI and suicide.

I am afraid I am right. I hope I am, because the answer is fairly straightforward: SSRIs don't cure PTSD, so don't Rx them anymore to vets with various combat-related mood problems.
Give them prazosin if they have sleep disturbance, and give them the empirically validated psychotherapeutic strategies for PTSD: relaxation, cognitive therapy, in some cases some exposure therapy, support groups, family education, etc.

Combat PTSD is very difficult to treat. Tragically, without SSRIs, there will still be suicides among these people serving our country. For a lot of people with combat PTSD, there just won't be a cure - just management. Let's help the vets manage this without putting them at any greater risk for suicide by handing out the SSRIs like candy, or as if it were all we have for treatment of PTSD - cuz it is not all we have.

March 20: more JAMA backpedaling on COI / Robinson

Over at JAMA, the COI issue continues to roll on. On March 20, JAMA posted a letter from DeAngelis, explaining how JAMA has been virtuous throughout the Robinson/COI deal --essentially, since Robinson had not received pharma money for this exact specific Escitalopram study in 2008, he decided that it was unnecessary to note that he has been a hired spokesmodel for the makers of escitalpram; others later pointed this out, in a letter to JAMA, and JAMA had to acknowledge.

At this point, WSJ blog picked up the story and discussed the issue.

http://blogs.wsj.com/health/2009/03/13/jama-editor-calls-critic-a-nobody-and-a-nothing/

I blogged abt this study here:
http://www.medsvstherapy.com/2008/07/license-please-or-what-happened-to.html

In a Mar 20 JAMA letter, DeAngelis described the WSJ blog coverage as "sensationalized media accounts..." She also declared: “JAMA editors take issues of undisclosed conflicts of interest seriously...In investigating this allegation, we followed our standard polices and procedures..."

1. “Sensationalized”?
The blog was not “sensationalized.” It was reporting and discussing an important issue: this Robinson article had a ridiculous approach to analyzing the data, quite at odds with the quasi-survival analysis illustrated in the same article. There has already been the (unsupported) report of DeAngelis name-callling over this issue. I think the "sensationalized" description amounts to more name-calling.

2. Even more ridiculous:
Well, this “standard procedure” to deal with COI seems all fine and good. But what if JAMA assumed, with all of the abundent evidence, that there WILL be researchers trying to scam the system, and "investigate" proactively, rather than when caught?

Here is all ya gotta do:
look at the lead author. Look at the drug seemingly promoted. Figure out the pharmaceutical company that markets the drug. Enter author name and drug company into Google. Hit enter.
That is how I quickly and easily discovered Robinson’s COI when the article appeared.

Is it that hard? Is there no editor at JAMA with a computer with internet access? No one can assess this proactively? If you say you take this seriously, then take it seriously. Call me up – I will do it for ya.
Maybe it is the age-old strategy: it is better to ask for forgiveness than for permission. Is JAMA hoping no one notices these COI, then putting together a good press release on the portion of occasions when it is detected?

DeAngelis, and JAMA, falter on one simple scientific concept: the theoretical threat of bias must be respected. In other words, the mere presence of bias indicates that the scientific community should be conservative in accepting the results of such a study, and the burden is on the pharma-sponsored researcher to design methods, and report this design in the manuscript or, when not permitted by space, to be gracious and understanding when requested for such information. Anything less is less than scientific. If you are on the payroll, it is fair for us to assume COI. Even if the pharmaceutical company did not pay you for this specific exact study.

How can JAMA fail to get this? A guess: The editors are medical doctors first, and scientisits second. Medical doctors, AKA physicians, are generally not scientists. The exceptional medical doctor who goes out of his or her way to receive education, formally or informally, in science, may step up to the level of scientist, along with being at the level of clinician. Either way: the rules of science do not change. Science does not care what letters are behind your name. Science does not care how many lives you believe you have saved. Science does not care about your knowledge of Latin. Science cares about hypothesis testing, empirical evidence, and bias. If you conduct a study evaluating a patented drug whose manufacturer has paid you any money in the past several years, you are tainted. That is just the way it is. Do the right thing: share the info regarding the taint. Game over. Please try again.