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?"

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Sarebear said...

Excellent quotes.

I love your notes. I read the other posts, but couldn't really pull my thoughts together to comment.

Everything here is good, but the two things that especially jump out at me are the following:

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.

, and the second to last one about making sure older patients aren't even unconsciously treated as though they don't need quite as much follow up.

EXCELLENT! I haven't been commenting much lately, but I've been here.

Were you ever going to do a second day post of that one conference you went to maybe a month ago or more, with some of the wierd subjects? Ok, wierd to me, anyway. Lol!

Steve & Barb said...

Thanks, Sara. Getting more done from that conference has been nagging at me for a while. There's some good stuff there. I'd like to get that done... lessee here... where are my notes...

ClinkShrink said...

"Telling prescribers that people with depression starting antidepressants should be followed at least weekly at first should be no different."

And public psychiatrists will do this how?? I'm with the FDA on this one. Public institutions already have enough regulations telling us how to practice. Twice weekly appointments just won't happen no matter how many regulations the FDA passes.

Dinah said...

Wow, what an excellent post. Proud to have you as my co-blogger (even more pleased that you didn't post humiliating pics of my dog).

It's kind of like the whole vaccine question; well maybe not really, because the overall data for reduced illness/death with vaccines is more dramatic, though certainly there are those who feel that they've had quirky/fatal/disabling/unpredictable responses to vaccinations.

When you hear someone talk about an ideopathic but horrible event following the start of one of these medications (the NYTimes magazine, I think it was there, had a story some time back), it's hard not to wonder, and wonder we should. Still, I clinically haven't ever seen someone not previously suicidal (and I'd guess that at least half of people who present initially with depression are having some suicidal thought at the time of initial presentation), that began after the introduction of SSRI's. I've seen weird side-effects, I've seen people not tolerate the meds, but I haven't seen anyone with an extreme reaction. I've seen lots and lots of people say the meds help them (no pharm ties, what can I say?). It would be hard to stop using them.

NeoNurseChic said...

I haven't taken many antidepressants I guess, and the ones I have taken were all prescribed to treat headache - except for prozac which was prescribed to treat "fibromyalgia" (I don't have fibromyalgia.....). But 2 of them had profound effects on my mood (not necessarily increased suicidal thoughts) that I'll never forget. It does make me a little leery of trying similar meds only because it took a looooong time to realize that the meds were changing me and not that I was just becoming a different person...

I've probably shared both stories in brief before. On prozac, I didn't care about anything at all. I was actually started on the daily dose, but went to my neuro with tremors in my hands and said I MUST get rid of those because I couldn't play the piano like that, and he put me on the weekly dose. I got a 42% on my 3rd chem exam, and then said, "Oh well...what's for dinner?" I just didn't even care - this from someone who, up until college, had never received a B in her entire life for a final grade. I had gone to lunch with my mom one day, and I really don't remember what we were talking about, but my mom said to me, " need to call the doctor. You are a different person on the prozac and you don't give a crap about anything or anybody, including yourself. You need to get off this...NOW." Too true...too true.... I was so detatched from the world - a nuclear war could have started, and I would have not cared at all. And those who know me closely know that I'm a highly opinionated, passionate person.

The other was with Cymbalta. My 2nd post on my blog was actually in reference to the Cymbalta commercials, because I find their commercials enticing and sometimes have to remind myself that it's not the right drug for me! Here's the link to my post on that (it's very very short): Cymbalta Post I still receive tons of hits to my blog by people who search for "cymbalta song" and other weird cymbalta related search questions. But at any rate - I cried just about every single day that I was on cymbalta. I was suddenly so much more depressed that I could hardly stand it. I was also anxious as hell. My heart rate was racing so fast on that med - I was shaky, anxious, and just cried nonstop. I have no idea why I reacted that way to it.

It's hard - because so many times, I don't see the actual effects of what meds do to me. However, those two meds stand as a very strong example that these meds have chemicals that actually have the power to change your mind...change the way you think, the way you act, and can, for some, change your entire personality. It's sometimes rather overwhelming when I realize that. As much as I would like to be free from depression, anxiety, and my ADD, I know that first and foremost, I do not want to become a different person. I may hate a thousand things about myself, but ultimately, I want to be ME and get through those things. I know these drugs don't change who a person is for everybody, but that was shocking the way that happened to me! What's more is that they had such a powerful effect, that it took prompting from others to actually realize that I had become some other person. I didn't know it.

I still don't think that we should just stop using SSRIs and antidepressants in general. I just have a much more profound respect for the power of these drugs to wield amazing changes in ones thoughts/personality. I can't say that I experienced sudden new-onset suicidal thoughts from these meds. I've had suicidal thoughts way before I ever took any meds for headache or depression, etc. I don't recall having a sudden increase in these thoughts while on either of those meds, but frankly I don't really remember. I think it would have struck me a bit more......I dunno...

Roy - I'd also love to hear about the rest of your conference! Did you ever happen to read the article about the Zonisimide Induced Suicidal Ideation? That's the one that my psychiatrist co-authored (SH). I just find comorbidities to be a very interesting topic, given my strong desire to study all things neuro/headache. More comments on that some other time.

Carrie :)

Anonymous said...

Thanks for the posts about these hearings, it has been interesting. A quick question about the increased suicidal ideation of children on antidepressants: is it possible that the antidepressants increase the children's willingness to admit to having suicidal ideation rather than the thoughts themselves?

Liz said...


I'm a student at University of Michigan Law School, and I am writing a paper for FDA Law precisely about this topic and some related law issues. I can't seem to find any source that goes into detail about the FDA's findings or the new black box language from last week's meeting, aside from your blog. However, some part of my doubts that I can use a blog as a source. Is there any way either I can cite you (directly) as a source or that you could point me in the direction of a cite-able source with more detail than the major media outlets? Thank you so much either way! My email is
-Liz S

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