I keep apologizing for being tedious and obsessed about these two articles published online in the Archives of General Psychiatry:
• Benefits From Antidepressants [March 5]
My apologies are ingenuous. I guess I keep apologizing because I know it’s just plain boring. I doubt that anyone reading this blog really believes Dr. Gibbons et al’s assertion that the whole black box warning on antidepressants about youth suicides in 2004 was wrong – some kind of over-reaction by the FDA. If you’re a person who sees depressed kids [a psychiatrist or other mental health worker], I doubt that you think SSRIs are particularly effective in kids who are depressed, particularly mildly depressed. And if you’ve kept up with this business, you are probably suspicious of Dr. Gibbons’ objectivity on this issue in that he’s spent the last eight years trying to find a way to debunk the black box warning using several different methods, including jumping on the small blip in adolescent suicides in the year the warning was issued – a blip that disappeared the following year and thereafter. And if you read either of these articles, you know that they contain almost no data, and the descriptions of the methodology and statistical analyses are beyond the reach of any psychiatrist I’ve even met. But even if they were understandable, it would be impossible to check things because the information just isn’t around to look at. But if you’re reading this blog, you’re an unusual person in that it means you care about the publication of misleading articles in our literature. Most people don’t give that a lot of thought. They’re much more likely to read these conclusions in the abstracts, or even more likely be handed or shown a copy by drug reps visiting doctors offices:
Conclusions: Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the first research synthesis of suicidal thoughts and behavior in depressed patients treated with antidepressants that examined the mediating role of depressive symptoms using complete longitudinal person-level data from a large set of published and unpublished studies.
Conclusions: To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.
I don’t believe either of those things are correct. But worse, I doubt that either of these articles show either of those things. But worst of all, there’s no possible way to rationally refute those claims because, when it’s all said and done, there’s not enough information available either in these articles or elsewhere to even try. These are faith-based articles from people who haven’t earned the right to have faith bestowed on them. So all I can do is explain why my faith level is so low, and then move on to something that won’t put people to sleep. So here are a few of my complaints just to get them off my chest.
My first complaint is about the source of the data. It wasn’t in the first article [February 6], it was going to be published with the second article [yesterday]. Being impatient, I periodically tried to figure it out to no avail. Along the way, I did learn that the NIMH Treatment of Adolescents with Depression Study [TADS] had been deceptively reported, minimizing the suicidality in kids taking Prozac [significant I…, significant II…, significant III…]. Even when the second article was published, I couldn’t find one of the studies until a commenter ran it down and found a clue that lead me to it listed under another drug. That was because everyone in the study was also on Strattera® along with Prozac®. Strattera® is an ADHD medication – a Selective Norepinephrine Reuptake Inhibitor. In fact, it was a Strattera study, and the patients didn’t necessarily meet the criteria for Major Depressive Disorder. So I finally located the four studies analyzed by Gibbons et al all to reach the conclusions above about children and adolescents.
Here they are redrawn to have a uniform Children’s Depression Rating Scale-Revised [CDRS-R] full scale display [references in come rest a while II…]:
The top two studies [X065, HCJE] were the original ones used to get FDA Approval for children and adolescents [before the black box warning]. TADS was the NIMH study but they didn’t use the CBT or Prozac+CBT groups, cutting off a a sizable chunk of the suicidality. For the suicidality analysis, they used the score on the CDRS-R Item 13, a method abandoned by the FDA as inadequate. For efficacy, they only used the first 6 weeks [darkened in]. And Study LYAQ was an inappropriate choice because of admission criteria, the concomitant use of another potent drug, and the low starting CDRS-R scores [they allowed the concomitant Strattera, but not the minimally effective CBT?]. These were all data manipulations bound to affect the outcome. In addition, they selectively quoted the literature eg "The National Institute of Mental Health–funded STAR*D trial found a 67% remission rate for patients who finished all 4 phases of the trial" [which was a hypothetical, hardly a finding]. Their statistical methods and manipulations were unintelligible, presented as fact without specific methodologies identified or illustrations. The figures and tables were impenetrable. And why was it available full text on-line, then removed? And at least with the child data, why does the reported efficacy of this analysis sound better than any of the four studies used to generate it?
This is an important topic – giving medications carrying a warning of suicidal risk to kids. If someone is going to say that there is no risk and that the medications should be widely used because withholding them is harmful, the evidence should be solid and presented in a way that is accessible to psychiatrists and other physicians reading the material to judge for themselves. This article fails to do that at even a minimal level. It’s hard for me to imagine that presenting a retrospective analysis like this with this level of obfuscation was not deliberate. And it’s equally hard for me to imagine that the Archives of General Psychiatry would think that their readers would understand [or accept] this kind of presentation. But I’ve said enough. Time to put it to rest…
Mickey I have just “tweeted this”: Doctors:Read 3 parts of this and write a letter to the Ed of Archives of General #Psychiatry speak up and stop the BS and left the link to this post. I would encourage you and other like-minded doctors to write to the publication itself and get a rebuttal type Editorial printed, it’s the only way to take this kind of information and have something good possibly come from it. Otherwise, I think we all know a lot, are disgusted, and then it stops there…. instead of putting it to rest, I’d like to see the doctors that are disgusted w the entire profession, data burial, studies that are based on BS they are supposed to be considered for basis of verification for even rx’ing a drug to patients…speak up and take over this process with LOUDER voices. Your blog is nearly the only one in a vast wilderness speaking into the darkness, get a choir going.
PS- My perspective comes from knowing things were “shady’ in the pharma department, to then finding out terrific details on this blog of data and studies most of us in this mental health world have read…so it seals the deal with what we suspected, but at the end of the day there are parents with dead children from SSRIs, there are parents who have watched with horror there children be harmed in permanent ways from the drugs or watched them nearly die from behaviors on SSRIS, there are patients reading who suffer life long side effects from taking SSRIs and other psych meds, who sit back and at the end of the day read this stuff and say “now what”? it (the great details in posts like this) is like rubbing salt in the wounds we already have…there are forever changes that have happened to us. As a parent, I can read this blog post and think “write a letter!” but why not depend on the very doctors who still prescribe these meds to do that instead? or instead of the word “depend”, “demand”? Be the voice beyond the pages of blogs…for those who have suffered and will never get their life they once knew back….
Thank you.
it seems to me that your blog provides data and opinion that is without an equivalent in the mental health information space
you explore important aspects of treatment with an objectivity, perceptiveness and thoroughness that is absent in an information space limited to discussions of clinical trials
Thanks,
I’m working on a letter, but to be honest, I’m going to take a breather for a few days. These two articles are just too infuriating, so I am going to watch a few clouds for a couple of days before starting so I’ll write something rational.
Thank you Mickey, and I understand the need to think and process the information before writing, and gathering your thoughts about it.
Thank you for this and your other blogs. They are not boring (though I guess you feel you are preaching, as it were, to the converted) and the content (and literary quality!) is appreciated. Of course we should all be able to expect honest information when it comes to medicines – but there is something deeply alarming when corporate profits and personal gain come before our children’s health. I have the joy of helping youngsters (and adults too) to discover safer alternatives.
Mickey, It might be worthwhile to look into writing something for BMJ. They were the first to draw worldwide attention to TMAP, with a writer in the US.
As someone working on a letter to give my neurologist and primary care provider about my history with the psychiatric industry for the purpose of petitioning them to keep me free of psychiatric coercion in the case that one of the lesions on my brain (MS) should cause dementia, I find it very refreshing to read this, even though I can’t do the math.
I do have a little bit of a grip on logic, and have found that the thinking in psychiatry writ large has not moved far from the thinking that kept perfectly sane and unaffected graduate students locked up in a ward in the seventies, because once they were determined to be “insane” everything they did was interpreted as a symptom of their disorder.
Declaring all disorder to be biological and pretending that drugs can fix it just adds another layer of tautology with the caveat of “treatment resistant”. Some drugs can be useful to some people some of the time, for some reasons; but the number of people who need to be on medication for life is probably very, very small, I think.
I can lay the worst years of my life, and even my first IV and ride in an ambulance (at the age of 40) on the doorstep of psycho-pharmacology (a grand mal seizure thanks to benzos). And the ringing in my ears.
Every attempt to reign it in is appreciated by this woman. Life is hard sometimes, and though I have learned and honed many skills in my lifetime, I’ve found that becoming an old woman with a psychiatric label just makes everything harder—but not as hard as it was when I was being fed cocktails with the threat that I would become a full-blown manic depressive with psychotic effect if I didn’t. The psychiatrist I’d seen the longest apologized to me for those cocktails and finally admitted that all the mood stabilizers, anti-epileptics, and anti-psychotics were contraindicated; but the label remains.