Researchers Refuse To Acknowledge Anti-Depressant Suicidality Induction In Study Where It's Clearly Present

It's difficult to properly headline this post because the underlying study I'm addressing here is one of the most annoying I've run across in ages. Perhaps I am being uncharitable in my assessment and if someone wants to slap me about for being excessive, have at it. But, yes, here we have a study (pdf here) examining suicidal behavior and suicidality and self-harm in teens who are on anti-depressants or anti-depressants and CBT and the researchers canot even make themselves state the obvious. I'll get to the obvious in a minute.

The study was just published in the American Journal of Psychiatry and its authors include many of the usual suspects of child psychiatry, including Boris Birmaher (Paxil Study 329), Benedetto Vitiello, Graham Emslie and, drum roll, the controversial Martin Keller of Brown University and Paxil Study 329 fame. Here they were trying to examine suicidal behavior in teens with treatment resistant depression and establish what were some of the predictors of such behavior.

To do so, 334 patients aged 12 to 18 had to have already been on an SSRI for two months and had to still be experiencing depression. So treatment resistant depression for these researchers was failing on a trial of one anti-depressant. Hell, even the loosey-goosey FDA requires failing two anti-depressant trials to get to that stage.

The teens were then put through a very rapid taper of their failed SSRI over--brace yourselves--two weeks. Unless they were on Prozac. Then they were simply taken directly off the drug even though they were taking it at 40 mgs. a day. I have no idea how such experienced researchers could justify such a quick taper and why their review boards would approve such a protocol. Such rapid tapers of SSRIs can induce suicidal behavior and otherwise mess people up. An accompanying editorial describes the study design as "elegant." I guess elegance ain't what it used to be.

"Medication taper: Subjects were tapered to discontinuation from their initial medication by decreasing dosages over a period of 2 weeks, except for those who entered the study on fluoxetine, for whom the medication was simply discontinued, due to fluoxetine’s long half-life."

Then the teens were put right onto either an SSRI (Prozac or Paxil) or were put on Effexor. The teens were subdivided further into groups getting an SSRI-only, Effexor-only, SSRI plus CBT or Effexor plus CBT. They were then evaluated for three months for suicidal behavior.

Guess what? There was plenty of suicidal behavior and several actual suicide attempts in the study. What's more, at some point in this lengthy, multi-center study, researchers decided to stop using Paxil for one of the SSRIs and switched to Celexa "owing to concerns about the efficacy and safety of paroxetine." How nice. (Paroxetine is Paxil's generic name.)

"Higher rates of suicidal (20.8% vs. 8.8%) and nonsuicidal self-injury (17.6% vs. 2.2%), but not serious adverse events (8.4% vs. 7.3%) were detected with systematic monitoring [the lower numbers are for spontaneous self-reporting methods as opposed to doctor monitoring]. Median time to a suicidal event was 3 weeks, predicted by high baseline suicidal ideation, family conflict, and drug and alcohol use."

While I can appreciate the role that baseline suicidal ideation, family conflict and drug/alcohol use could potentially play in suicidal behavior, for the researchers to insist in the study, as they do, that that's all there was to it amounts to intellectual dishonesty.

Why's that? Well, the patients were on an SSRI which failed them and which they were taken off of quite rapidly (far more rapidly than most docs I know would approve of) and that could certainly account for at least some of the baseline ideation. Then they were put onto a subsequent anti-depressant before properly washing out of their previous anti-depressant and, then, at an average of three weeks, the ones who had a suicidal event had a suicidal event. And they are blaming this on outside factors when just about anyone who knows anything about anti-depressants knows it is the first month or so on a new drug (especially after a fast taper of something else) where tons of agitation and suicidality occur.

But the only mention the researchers make of potential issues with anti-depressants is where they note:

"In those participants with high suicidal ideation, treatment with venlafaxine, compared to treatment with an SSRI, was associated with a higher rate of either a suicidal or nonsuicidal self-injury event."

OK, so Effexor is associated with a higher rate of suicidality in the studied teens. Other than that, the anti-depressants aren't implicated at all--even though each and every one of the teens in the study who experienced suicidality issues or engaged in self-injury was on an anti-depressant and had just basically been put on the anti-depressant in question.

As I said before, elegance ain't what it used to be. Neither is honesty.

BTW, the authors are careful to hold CBT harmless here, noting that due to the rather prompt occurrence of suicidality and self-injury that patients who were in a CBT arm of the study hadn't had a full "dose" of CBT.