Saturday, December 16, 2006

What's Inside the Black Box? FDA Antidepressants Hearing, pt. 2

black box

[posted by Roy]

A couple days ago, I reported on the results of the FDA Psychopharmacologic Drugs Advisory Committee's hearing on December 13, 2006, on the FDA's plan to add a black box warning about the increased risk of suicidality in young adults. (I tried to get this done earlier, but just didn't have the time.)

Here are some notes I made at the hearing...

Sheila Matthews, from, suggested requiring MedWatch info on all pharmaceutical advertising. I think this is a great idea. MedWatch is the voluntary, side-effect reporting mechanism for the FDA. Few prescribers and fewer consumers use it to report side effects. They should go one further and make it very easy to report side effects... almost as easy as googling the side effects.

There were two out of state attorneys who brought a number of their clients to testify. There were also at least two people there testifying for the Church of Scient ology's C C H R (and making excellent points, I might add, about Lilly's reported lack of following through with their promise 15 years ago to provide additional data. There were quite a few who lost family members tragically after taking only several doses of medication. It is indeed hard to understand how a chemical can cause one to conduct such complex, planned behaviors. Yet, listening to their testimony, it was hard to wonder how their response to these antidepressants could not have contributed to their deaths.

Heidi Bryan, from the Feeling Blue Suicide Prevention Council, pointed out that a big part of the not-enough-follow-up problem was due to the lack of parity for mental health treatment. Even Medicare charges 2-1/2 times as much for co-payments for outpatient mental health diagnoses than they do for the same symptoms caused by non-psychiatric diagnoses (e.g., major depression vs hypothyroidism).

I think that managed care and pharma has so convinced folks that taking a pill is just as effective as talk therapy, that there is now a backlash that will soon require these companies to drop their discriminatory policies.

All of the voting committee members, including Wayne Goodman, Gail Griffith, George Armenteros, Andrew C. Leon, Marcia J. Slattery, Susan K. Schultz, Jean Bronstein, and the chair, Daniel S. Pine, repeatedly pointed out the importance of balancing any labeling changes with language which emphasizes the need to weigh the relative risks of nontreatment with those of treatment, even comparing the risk of treatment with that of non-treatment. In fact, when the vote came up about extending the language in the black box to include the young adults, two members voted against (Griffith and Pines), while the other six voted for it under the condition that balancing language be included as well. They told the FDA that they wanted to review the draft language prior to making a final decision.

Joe Glenmullen, who authored "Prozac Backlash", testified, as well. He and others state the the FDA has been tricked by the drug companies, by not being given complete information about all clinical trial results.

So, then the committee deliberated for a few hours. I must say, the committee members rather awkwardly, but repeatedly, made several important points...

  • The FDA needs to make the drug companies collect and provide better data.
  • There is inadequate data on this "activation syndrome", referring to akathisia, agitation, and anxiety apparently induced by antidepressants in some individuals.
  • Collecting pharmacogenetic data might help in determining which individuals might be at higher risk of developing this and other side effects.
  • The FDA is not collecting adequate data to differentiate between suicidal thoughts and suicidal behaviors and attempts. The pharmaceutical companies need to be directed to supply this type of fine-grained data. The fact that the currently reviewed data on "suicidality" makes it impossible to differentiate these two important characteristics suggests that any change in warning language needs to be carefully worded.
  • The committee insisted on the FDA adding balancing language to reflect not only the increased risk of "suicidality" in young adults, but also the other side of the coin -- the increased risk associated with untreated depression. Additionally, they'd like language which refers to the apparent protective effect of these drugs in older adults, especially in seniors. It was noted that this would be the first time that the FDA has included in a black box information of a positive nature.
  • They are concerned about the unintended consequences of decreased access to depression treatment as a result of the black box warning. Recent CDC information was noted, indicating that since the 2004 pediatric black box was added, prescriptions in kids are down, while suicides are up. This trend has already been noted in adults, and the fear is that it will only get worse with language that extends to young adults.
  • The "25 to 30 year old" group mentioned in Part 1 was not chosen scientifically. It just fit the data. Thus, there is nothing special that happens when you turn 25 or when you turn 31to alter your risk. Because of this, they considered instead using language like "young adults", but this idea didn't seem to be too popular.
  • Some of the possible explanations discussed for the biphasic nature of the data (higher risk when younger, lower risk when older) included induction of mania, late maturation of frontal lobes so impulsivity and experience improve as you get older, and greater tolerance for uncomfortable affect with age. They agreed that more data would be helpful.
  • The committee also felt it was very important to emphasize the need for close follow-up when treating people of any age with depression. There was concern that it could sound like older people don't need to be followed as closely due to this "protective effect".
  • Finally, the FDA acknowledged concern about telling doctors how to practice, and crossing the line into federal regulation of the practice of medicine. However, it was pointed out that, when the stakes are high enough, as with clozapine, the FDA has had no trouble advising things like frequency of monitoring lab tests. Telling prescribers that people with depression starting antidepressants should be followed at least weekly at first should be no different. Hopefully, they won't wimp out.

I'll leave you with two good quotes.

"Maybe we don't need a black box on antidepressants. Maybe we need a black box on Depression."

"How many will die with the black box? How many will die without it?"

technorati tags:, , , , , , , , , ,

Blogged with Flock