Becky commented about the publications from the American Academy of Child and Adolescent Psychiatry below. If you haven’t read them, please do. The first one is from 2004/2005:
Do antidepressants increase the risk of suicide?
Suicidal thoughts and behaviors are more common during adolescence than at any other time, but suicide is more common among adults. In any year about 16 percent of high school students think about suicide and about 3-8 percent show suicidal behaviors. Fortunately, very few of them commit suicide. Children and adolescents with depression are much more likely to think about suicide and to attempt it than other children. Although not all suicidal children have depression, untreated depression increases the risk of suicide.
The Food and Drug Administration (FDA) described an increase in reports of suicidal thoughts and/or behaviors in children and adolescents taking antidepressants. But, there were no suicides in the cases they studied. Autopsies of teenagers who have committed suicide show that very few of them had traces of an antidepressant, making the link between antidepressant use and suicide even weaker.
Between 1992 and 2001, there was a large increase in the number of adolescents being prescribed SSRI antidepressants. But, during that time the rate of suicide among American youth ages 10-19 actually dropped by more than 25 percent. This was the first time in nearly 50 years that the suicide rate declined in young people.
Why did the FDA issue a black box warning?
In 2004, the FDA reviewed 23 clinical trials involving more than 4,300 child and adolescent patients. These patients received any of nine different antidepressant medications. No suicides occurred in any of these studies. All of the studies the FDA reviewed measured suicidal thinking and behavior by using "Adverse Event Reports." These report the spontaneous sharing of thoughts about suicide or potentially dangerous behavior made by a patient (or reported by the patient’s parent). Such "adverse events" were reported by approximately 4 percent of all children and adolescents taking medication, compared with 2 percent of those taking a placebo.
A more recent study found that the risk was even smaller-around 3% in those on medication and 2% in those on placebo. Most of these events were increases in suicidal thoughts. Only a few were actual suicide attempts, and NONE were suicide completions. Through careful monitoring, the development of a safety plan, and the combination of medication with psychotherapy, the risks for increased suicidal thoughts can be managed. For moderate to severe depression, there is benefit in the use of medication because of a higher rate of relief, and more complete relief, from depressive symptoms than not using any medication.
Since the FDA issued the black box warning, there has been a decline in antidepressant use, but an increase in completed suicides in adolescents in both the US and the Netherlands. Although it is not yet clear how these trends may be related, this has been the first increase in the adolescent suicide rate reported in over a decade.
Prepared by the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry in consultation with a National Coalition of Concerned Parents, Providers, and Professional Associations
This document was developed by the American Academy of Child and Adolescent Psychiatry’s Committee on Community-Based Systems of Care with partial funding from the Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Mental Health Services
Food and Drug Administration Approval
The Food and Drug Administration (FDA) is responsible for the regulation of food and drug safety in the United States. FDA approval is a complicated and lengthy process. Generally, medication is granted FDA approval when it is found to be safe and effective for a particular diagnosis at a given dosage range for people of a particular age range as determined by evidence based research. When a medication is not FDA approved it is considered “off label”. It is important to note that the absence of FDA approval also does not indicate that a medication is not effective and safe. Pharmaceutical companies may not choose to dedicate the necessary resources to seek FDA approval. Medication used in the treatment of youth with mental illnesses is often used “off-label”, as is frequently the case in the medication treatment of pediatric physical illness. There are many medications approved for adults that are used off-label for youth. Off-label prescribing is very common, and the parent or guardian should ask the youth’s provider about the supporting evidence and agreement among other doctors that the medication is effective and safe. Such uses may include indications, dosages or age ranges which differ from those formally specified by the FDA. It is ethical, appropriate and consistent with general medical practice to prescribe medication off-label when clinically indicated. The prescriber or pharmacist can advise whether a specific medication is FDA-approved.
Some psychotropic medications have FDA Black Box Warnings. Medicines with black box warnings are still FDA approved, but their use requires particular attention and caution regarding potentially dangerous or life threatening side effects. Selective Serotonin Reuptake Inhibitors (SSRI’s) carry a black box warning that they may cause suicidal ideation or behavior, although the most recent review of the evidence is not conclusive that SSRIs increase suicidal behavior. Families should work in consultation with their child’s physician or other mental health professional to develop an emergency action plan, called a “safety plan”. This is a planned set of actions for the family, youth and doctor to take if and when the youth has increased suicidal thinking. This should include access to a 24-hour hotline available to deal with crises. AACAP recommends that family members discuss this with the provider if they are uncertain about a black box warning…
This is a guide to protect vulnerable Medicare and Medicaid populations, yet it goes on to recommend the AACAP guide above:
Yes there is something terribly wrong. I wrote a blog post quite some time ago in which I pointed out that Off Label prescriptions for psychotropic drugs and Medicaid fraud must in fact be endorsed by CMS; it is the only plausible explanation for the fraudulent claims STILL being reimbursed—in spite of how many lawsuits?! http://ow.ly/dHLks The lawsuits are for appearances only, IMO–retrieving a very small % of what was defrauded from the American people.
Re The AACAP
“They’re apparently part of the medication scene …”
“There’s something terribly wrong here…”
1BOM, though they are jumbled I think you would find it worthwhile to click through and review the various links below. They are not reassuring:
“After a year and a half of research, membership surveys, and discussion, in June 2011, AACAP’s Council approved the formation of a political action committee (PAC). A PAC is a committee that raises money to make political contributions to candidates for public office that support their issue or industry. ”
https://aacap.confex.com/aacap/2012/webprogram/Session9312.html
Chair Robert L. Hendren
Robert Hendren AACAP President 2007-2009:
Mina K. Dulcan, M.D., editor extraordinaire, 1997-2007.
Hendren, Robert; Anthony, Virginia Q.
http://psycnet.apa.org/psycinfo/2007-18374-001
Transparency Portal
American Academy of Child and Adolescent Psychiatry Portal on Transparency
AACAP “A Message on Transparency by AACAP President Robert Hendren”
http://www.aacap.org/cs/root/AACAP.Transparency
During that same tenure, and from that same Transparency Portal Page:
“Guidelines on Conflict of Interest for Child and Adolescent Psychiatrists
Last Reviewed and Approved by Council on January 30, 2009”
http://www.aacap.org/cs/root/physicians_and_allied_professionals/guidelines_on_conflict_of_interest_for_child_and_adolescent_psychiatrists
See APPENDIX I Acknowledgement and Disclosure of Conflicts of Interest by the Consensus Building Panel Members. In addition to Dr. Ryan you will also note Dr. DelBello.
According to this great piece on Paul D. Thacker in Nature, questions had been raised beginning in 2007 about industry payments to Dr DelBello.
http://www.nature.com/news/2009/160909/full/461330a.html
In fact, the “background” section of the guidelines above mentions a 2007 Harris New York Times paper that is most likely the one that has the Dr. DelBello quote that led to Paul D. Thacker’s investigation in the first place.
http://www.nytimes.com/2007/05/10/health/10psyche.html?pagewanted=all
It was Feb. 2008 that AACAP convened its consensus panel on Guidelines for Conflict of Interest and that AACAP selected Dr. DelBello to sit on that panel.
eAACAP
Casting a Wide Net to Nurture Mentally Healthy Children
Robert L. Hendren, D.O.
AACAP President-Elect
http://www.aacap.org/cs/root/meetings_and_online_cme/annual_meeting/54th_annual_meeting/eaacap
Part way down the page lists the advisory board picked by Dr. Hendren. You might notice some of the names, including the chair of AACAP’s Continuing Medication Education (CME) Committee Dr. Jeffrey Bostic. That name might be familiar because of this story from 2009:
http://m.cbsnews.com/fullstory.rbml?catid=42840774&feed_id=76&videofeed=43
AACAP
Bipolar Disorder Resource Center
http://www.aacap.org/cs/BipolarDisorder.ResourceCenter
Last updated July 2009
At the bottom of the page, AACAP singles out 2 websites for families visiting their site:
“Related Websites
There are many organizations that provide support groups for families that have a family member or child with bipolar disorder. Two such organizations are the Child and Adolescent Bipolar Foundation and the Depression and Bipolar Support Alliance.”
“Child and Adolescent Bipolar Foundation”
Now called the Balanced Mind Foundation. Here is their Scientific Advisory Board:
http://www.thebalancedmind.org/about/staff/cabf-scientific-advisory-council
Rereading the internal SKB/GSK memo about 329 and Dr. Ryan’s letter in JAACAP I get the impression that they all may have thought that they would have had a fundamentally positive study (the “signals” of efficacy were there, the endpoints all trended in favor of paroxetine, …etc) were it not for the high placebo response. And, that that high placebo response lead to the study appearing to have not shown paroxetine’s effectiveness when it was actually there.
Essentially, if Nero (paroxetine) hadn’t fallen off the chariot (i.e., the placebo response rate had not been unusually high) then it would have gone on to win the race.
Letting this truly positive study be unfairly characterized as negative due to what would then just be a lack of it being sufficiently powered would then lead to Eli Lilly’s pharm reps going to town with that information. And, would lead to primary care physicians being even less likely to prescribe it.
An aside: Allostrata reasonably points out that conflating paroxetine and all SSRIs is a fallacy. Paroxetine may not be the best drug to use even if you believe SSRIs are of use. Fluoxetine is much more likely to be used in children today than paroxetine. Dr. Ryan does not appear to acknowledge that positive fluoxetine studies and negative paroxetine – at least in terms of how they were viewed – studies would not necessarily lead to fewer kids getting SSRIs, but would definitely have led to a smaller market share for SKB/GSK.
Be that as it may. It seems easier to explain that than the following:
What is one to make of the AACAP, in 2007/2008, at the height of the controversy regarding both Study 329 and Dr. DelBello, placing both her and Dr. Ryan on this consensus panel. We’re not talking about a rush to judgment. How could the panel even consider the possibility that Dr. DelBello’s and Dr. Ryan’s approaches might be in need of comment from the panel if the AACAP had already selected them as primary participants in the forging of the AACAP’s guidelines?
Perhaps in 2007/2008 pediatric psychiatrists across the country read about Dr. Ryan and Study 329 and the 2001 paper, and about Dr. DelBello’s funding and disclosures and her subsequent reactions, and said to themselves that these two would be among the few individuals they would most want providing them guidance on ethics.
Not that they should or shouldn’t be censured. No, that they would actually be considered apriori to be amongst the best suited to address the issues. Not in a research capacity. But on an ethics consensus panel.
We can’t know that.
We can know that that was AACAP’s judgment.
I listed a conjecture above for GSK’s and Dr. Ryan’s approach to what they possibly considered a positive study they believed would be unfairly maligned due to a lack of statistical power (due in turn to the high placebo response/natural remission). I am not attempting to defend the decision, nor condone it even of that conjecture is correct. However, at least the conjecture of their partially covert reasoning appears grossly consistent with their explicit statements.
The AACAP’s approach, at least as suggested by the information in this and the previous comment, appears possibly more opaque.
No matter how many times the word “transparency” is used.
If you have a graphic of the words “I Am Transparent” or “Transparent Portal” graffitied across a stone wall then now might be time to break it out.
Some of these behaviors of the guilds is clear enough. Whether their membership will continue to tacitly endorse it is another matter. Right now, it probably doesn’t seem worth fighting. But, these behaviors may begin to erode the trust placed in such guilds. So far, studied silence, counterattack and transparenciness have been effective in maintaining the credibility of such guilds with the government, with families, with other providers. Perhaps that will continue to largely be the case. If not, then perhaps there will be a grassroots effort within guilds to reflect upon these past (and present) behaviors.
Those who work directly everyday with children in clinical and research settings deserve a strong voice. All the more reason to care about the integrity of that voice.
You and I are not going to be that voice.
But something is not right. And thank you, 1BOM, for giving voice to that.
Annonymous,
I have perhaps more faith in the guilds, but you’re right, this has gone on for a very long time. I don’t think the JAACAP yet knows that it’s on thin ice. If they continue to stonewall, they’re going to lose an opportunity to maintain some version of their position. Once these things go bad, they go downhill in a hurry. The more I read, the more I think that the Pharma ties go deep and they are more vulnerable than they yet seem to know. That Guidance is pretty blatant. There is something very wrong…