From the beginning, and in the decade since, APA has protested the warning, predicting that it would prevent parents from seeking care for their children – and clinicians from prescribing antidepressants – and insisting that by far the greater danger was untreated depression. “We are concerned that the publicity surrounding this issue may frighten some parents and discourage them from seeking help for their children,” child psychiatrist David Fassler, M.D., told the 2004 panel. “The most important point that I can make is that the biggest risk for a child with depression is to be left untreated.”
Shortly after the FDA issued the Black Box Warning of possible suicidality in adolescents on antidepressants, the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry jointly established a website, ParentsMedGuide.org [Updated 2010], that said:
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.
What is a black box warning?…The FDA did not ban the use of antidepressant medications for youth. The purpose of the warning was to alert physicians and parents to watch children and adolescents to see if their symptoms got worse, or if they showed unusual changes in behavior. The FDA also specifically said that “depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions”.
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. … 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.[see also something terribly wrong here…]
And on the American Academy of Child and Adolescent Psychiatry website under the Depression FAQ, we read:
What should treatment consist of?
When possible, treatment for depression childhood depression should include both psychotherapy and medication. In milder forms of depression, it is reasonable to start with a psychotherapy, but treatment with a medication and psychotherapy should be considered for moderate to severe forms of major depression. Before starting treatment, a doctor will discuss it’s risks and benefits, as well as how the treatment should be monitored.
Are medications safe? Do they increase risk of suicide?
When prescribed and monitored carefully, medications are both safe and effective ways to treat of depressed youth. Fluoxetine or Prozac, a selective serotonin reuptake inhibitor, is the medicine that so far has proved most safe and effective. There are times, however, when other medications can and should be used. While medications have been associated with a small increase in thoughts of suicide, there is no evidence that antidepressants actually increase the risk of suicide. For moderate to severe depression, the potential benefits from medication treatment seem to outweigh the potential risks.
They get some credit for "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." But I’m afraid that, "the potential benefits from medication treatment seem to outweigh the potential risks" is actually a major flaw in this whole argument. Prozac® was approved early for adolescent depression, before the Black Box Warning was issued [top two graphs], but that was the only approval. Paxil® had the infamous Study 329 [lower left] and two other unpublished negative studies. And Zoloft® only eked out minimal significance at ten weeks by combining two negative studies [lower right]. So none of them support a claim of the kind of "potential benefits" their argument advertises [see tuning the quartet…]
So it’s hard to mount a rational explanation for why our two major professional organizations [APA and AACAP] are still making an assault on the 
Black Box Warning. Except for Prozac®, they’re advocating off-label prescribing for marginal efficacy at best. There’s unlikely much push from PHARMA now that the drugs are off-patent. In spite of the limitations, they’re still prescribing at a moderate pace. Seems to me they’d let this sleeping dog lie…
Black Box Warning. Except for Prozac®, they’re advocating off-label prescribing for marginal efficacy at best. There’s unlikely much push from PHARMA now that the drugs are off-patent. In spite of the limitations, they’re still prescribing at a moderate pace. Seems to me they’d let this sleeping dog lie…
Looking at this from a business perspective Black Box warnings are an opportunity cost for pharma. When doing this calculation pharma will make various assumptions as to market size, frequency of taking the medication, and the entire medication load of a patient.
These assumptions will vary wildly as they try to maximize their income and sales.
The hidden agenda is that once again we see pharma using psychiatry as a leader in removing a Black Box warning from one of these drugs they will then use the logical fallacy and straw man argument that all Black Box warning should be removed for the benefit of the patient.
Pharma has tried a Freedom of Speech argument in allowing sales reps to go off scrip when selling drugs. This has no basis in the law as a corporation is held to a higher standard of truthfulness in commercial speech.
Pharma has also claimed the doctor/patient relationship relieves them of any responsibility for prescribing, and that a doctor in their position of trust, should be allowed to prescribe any drug at any time. This shifts the liability to the doctor and the patient for the usefulness of any drug. This standard cannot be met due to the complexity of modern medicine, not to mention their complicity in disguising the true nature of risk and benefits.
From my perspective this is just another attempt to create a small crack so as to insert a lever and bring the whole Black Box warning system down.
Steve Lucas
Good points, Steve. The maneuvering will never stop – it is in Pharma’s DNA. As for where the locus of professional responsibility lies, it is squarely between physician and patient. In the traditional professional model that relationship is managed with confidentiality and discretion, and the standard of care has nothing to do with the FDA or with product package inserts. In other words, the FDA does not regulate the practice of medicine. The PPIs give guidance but they are not mandates, except in the domain of absolute contraindications.
It’s not rational. The policymakers at the APA and AACAP have a religious belief in the benefits of antidepressants. It’s hard not to infer this influences the thinking of their members as well.
What’s not rational? If you’re saying clinical psychopharmacology is not rational then you are not rational. The zones of uncertainty do not concern whether the major drug classes are effective in treating clear cut cases. The uncertainty concerns the boundaries between clear cut cases and milder or short lived cases, and the offsetting risks versus benefits in such cases. As for the “religious belief” of “the policymakers at the APA and AACAP,” lighten up.
The efficacy of the boundaries between “milder” and “clear cut cases” is hardly the only consideration in defining zones of uncertainty– and I think there are many. As Lucas notes, “disguising the true nature of the risks and benefits” is the real turd in the proverbial punchbowl, here, and that speaks to significant defects in what passes for informed consent these days. That’s another “zone of uncertainty”– and of liability and responsibility.
As for psychpharmacology being rational, well, perhaps in some academic sense there might be some evidence for this, but in the consulting rooms of many behaioral health centers, increasingly, that may be a bit of a hard sell.
The APA doesn’t actually require tithing or hold ceremonies with rituals and… oh, wait a minute, maybe they do– anyway, perhaps they aren’t actual religions, but let’s hope they don’t take on any more trappings of the pseudorelgions, like… oh, say, the Chicago School of Economics.
Sorry. It’s been a long day. Better sign myself off before I get in any more trouble.
Our esteemed blog author and host wrote: “So it’s hard to mount a rational explanation for why our two major professional organizations [APA and AACAP] are still making an assault on the Black Box Warning. Except for Prozac®, they’re advocating off-label prescribing for marginal efficacy at best…..”
With the phrase “it’s hard to mount a rational explanation,” I believe Mickey is implying that the motive is irrational.
I was directly responding to Mickey’s point, suggesting the irrational driver of this behavior was a religious belief, one type of irrational belief.
I thought my remark was obvious and harmless, but perhaps it was confusing. Thank you for the invitation and opportunity to clarify it.