Atypicals For Kids: Here Comes The Evidence

There was an interesting story last week in Psychiatric Times. It was a curtain raiser on what the reporter promises will be a big year of data for psych MDs. Lots of studies on using atypicals in kids and adolescents--I predict that these short-term studies will show limited efficacy with big weight gain in the kiddos. More clinical data on what anti-depressant combos work best--as if the dead horse hasn't been beaten enough. More data from the STEP-BD study on long-term treatment of bipolar disorder--even though I thought all the main papers came out last year and were pretty much a wipe out. In addition, there will be a recalculation of data from the CATIE study establishing which antipsychotics are most effective in treating schizophrenia--um, why are they going back to restate what the CATIE PIs have made clear over the last 18 months, namely that the atypicals don't work so swell for treating schizophrenia and have a host of gnarly side effects? Whatever.

But what really caught my eye was this:

"And new data on one drug, Zyprexa (olanzapine), will likely be submitted to the FDA this year in anticipation of earning a pediatric indication for either schizophrenia or bipolar disorder."

Oh my. After all the problems that have cropped up around Zyprexa's use in adults, Eli Lilly is pushing to have it approved for kids? That ought to be one very interesting filing with the FDA.

The other atypicals for which data is expected in treating kids are Seroquel, Geodon and Abilify. Not long ago, I ran into a study of Seroquel in kids led by Joseph Biederman, a professor of psychiatry at Harvard and a member of the advisory board for the pharma-funded Child and Adolescent Bipolar Foundation. Here are some highlights of the ongoing study from the clinical trials registry:

"This is an 8-week open-label study aimed at assessing the effectiveness and tolerability of Quetiapine [Seroquel], in the treatment of preschool children aged 4 to 6 years with bipolar and bipolar spectrum disorder. This is an exploratory, pilot study, seeking to determine whether Quetiapine is efficacious and well tolerated in the treatment of preschoolers with pediatric bipolar and bipolar spectrum disorder in this age group." (Emphasis mine.)

And:

"Subjects must have a DSM-IV diagnosis of bipolar I, bipolar II disorder or bipolar spectrum disorder and currently displaying manic, hypomanic, or mixed symptoms (with or without psychotic features) according to the DSM-IV based on clinical assessment and confirmed by structured diagnostic interview (Kidd Schedule of Affective Disorders and Schizophrenia Epidemiological Version). Bipolar spectrum disorder (or sub-threshold bipolar disorder) is operationalized as having severe mood disturbance, which meets DSM-IV Criteria A for bipolar disorder but meet fewer elements in criteria B (only require 2 items for elation category and 3 for irritability)."

This shit is fucked up on so many levels that you almost don't know where to begin. Here goes.

I am against sticking four to six year olds full of an antipsychotic, especially Seroquel. It's well known to cause weight gain in adults and creates so much cognitive slowing and the fifth of whiskey head the next morning that it is utterly unfair to give this to children. In fact, I think it's unethical, especially given concerns that the drug might cause dependency in some adults. The kiddos won't be doing so hot at pre-school the next day, methinks. The study's prospectus doesn't get into what dosage range will be evaluated.

But here's where things get bizarre to my way of thinking. There is no official DSM diagnosis for bipolar disorder in kids, so I am confused as to how you can even do a trial like this with a straight face much less with approval of Harvard's human subjects committee. "Bipolar spectrum disorder" doesn't exist in the DSM--it's a term being batted about by researchers like Fred Goodwin to capture even more people in the bipolar nexus than the docs already can with BPI, BPII and cyclothymia. Even more irksome is that the kids don't have to hit the same kind of manic/hypomanic highs that adults hit in order to get into Biederman's study.

Although Biederman's criteria looks tighter than most studies, I find it bothersome--irritating, even--that the general thumbs-up that this study will no doubt provide AstraZeneca will then be used by clueless PCPs and desperate parents to medicate kiddos who hit the ridiculous standards floating out there that kids only have to have certain traits of bipolar disorder for moments at a time in order to be considered as profoundly manic, for example, as the same symptoms in adults would. Except the adults would need the same constellation of symptoms over a two-week period.

Or am I the only one bothered by such inconsistencies?

I was at a local Barnes & Noble yesterday and ran into at least five books on bipolar disorder in kids. I couldn't even find a copy of The Bipolar Child, the book that kicked off the whole "your irritable child throwing rocks at other kids is bipolar and must take antipsychotics" silliness that's bouncing through our culture these days. I think studies like the above and Eli Lilly's expected FDA submission of Zyprexa for treating bipolar disorder and schizophrenia in kids show us just how far off the peg we are getting in America these days.