Mental Health Blogs

A new study is out in the American Journal of Psychiatry, a small pilot study, touting the use of Depakote in combination with various ADHD stimulants in children and adolescents aged 6 to 13 years of age with both ADHD and a so-called disruptive disorder. The study involved so few children–14 in the Depakote arm–that its findings aren’t robust at all, statistically. And yet the study is accompanied by an editorial trumpeting the future of child psychopharmacology.

Let’s deal with the editorial first. Its author Hans Steiner is a professor of psychiatry at Stanford and the author of a 2003 study in the Journal of Clinical Psychiatry reporting good results using Depakote to treat conduct disorder in adolescents. He and his Stanford colleague Niranjan Karnik write in the editorial accompanying the study:

“[M]ost experts in the field agree that aggression, especially emotionally hot, impulsive aggression, forms a legitimate target for intervention across a spectrum of psychopathology, including attention deficit hyperactivity disorder (ADHD), bipolar mood disorder, and posttraumatic stress disorder.”

OK, then.

“The future of psychopharmacology in childhood aggression and its underlying disorders is an important area of great need for more work along the lines demonstrated in this study. It is unrealistic to assume, as we have been for some time, that complex behaviors, such as aggression, will respond robustly to single psychopharmacological agents in all patients and all types of comorbidity, and yet the bulk of clinical trials are done with single agents. A more realistic assumption is that a careful blend of activating (like stimulants) and inhibiting (arguably valproic acid) agents will ultimately result in controls of main and downstream effects of neurotransmitters that produce remission of symptoms. This is especially likely in children and adolescents in whom development generates rapid shifts in neurosystems underpinning instrumental behavior such as aggression.

“This study points the way to a more complicated, but ultimately more realistic, polypharmacology in developmental psychiatry that should produce better results for our patients, rather than some of the unfortunate ‘polypsychopharmacology,’ where a high number of agents is combined in suboptimal doses in hopes of producing desired results.”

Look, I’m all in favor of getting away from the wild polpharmacy advocated by the Harvard child psychiatry crowd and others, which has resulted in tons of aggressive kids on antipsychotics for non-psychotic issues, but it is more than a little Pollyannaish to suggest that a little old pilot study is as suggestive for the future of child psychiatry as the editorial pretends.

What’s more, I’m really concerned that aggression in children is becoming such a defining issue in how our culture views children that aggression has become a force of evil to be stamped out. Much of this is driven by the culture of American schools these days, where behavioral calmness is everything and boys are to be firmly affixed to their chairs in class. I think we all know where Huck Finn and Tom Sawyer would be these days–headed to the nurse’s office for their noon-time meds. OK, I know I’m overstating things a bit there, but something has changed so dramatically in how we address childhood aggression these days that someone has got to push back a bit, even if it seems unreasonable.

The study itself comprises 14 youngsters on stimulants whose aggression didn’t abate and who were then put on various dosages of Depakote or were given a placebo (13). After eight weeks researchers reported that 57 percent (8 of 14) of the Depakote kids had improved on aggression scores while only 15 percent (2 of 13) had on placebo. That’s a sizable effect size of 42 percent, but with such a small sample size (and the researchers admit this) the statistical power is limited. This could be a result of chance or something else.

Joseph Blader, a professor psychiatry at Stony Brook University School
of Medicine in New York led the study. His and other study researchers’ pharma-funding conflicts are listed at the end of the study and they are epic: J&J, Lilly, Schering-Plough, Abbott Labs and so on. I’m concerned that this study blends funding from NIH and Abbott Labs. I wasn’t aware that it was common practice to mix funding that way.

So who are some of these kids? The study includes a case profile of one 6-year old boy:

“‘Freddy’ was a 6-year-old boy whose mother related a long history of attention deficit hyperactivity disorder (ADHD) symptoms and behavioral dyscontrol. She characterized his present difficulties as being ‘verbally and physically abusive.’ She stated that ‘he destroys property, defies authority, has no friends, hurts animals, and constantly annoys others.’ He was in frequent conflict with family members, peers, and school authorities. When not acutely upset, he was an affectionate, articulate, pleasant boy. His ingenuity and engaging character attracted other kids initially, but subsequent interactions discouraged them, owing to his inflexibility in accommodating other children’s desires over his own….

“At a 54-mg dose [of a stimulant], attention and appropriate participation in school improved, but aggressive outbursts persisted, including
incidents of throwing his desk over in response to directions to
conclude an activity….

“By his fourth week after randomization [meaning he was getting Depakote], his mother reported that he was ‘great,’ with ‘no problems at all.’ She stated, ‘He shows a lot less anger and is a lot more relaxed.’”

Poor Freddy is all I can say. I certainly cannot remember when not having friends at school and turning over desks counted as a psychiatric disorder. My entire elementary school in California should’ve come under suspicion for all the fights, kids flipping out, kids getting stabbed with a pencil in the arm (poor Ted Looney) and getting their hands slammed in windows (that’d be me, thanks to a little girl named Beth). How did we manage to survive and evolve into adults?

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Related posts:

1. Study: Medicaid Kids Get Antipsychotics At Four Times The Rate Of Privately-Insured Kids
2. JAMA Study Finds Explosive Weight Gain In Kids On Antipsychotics
3. Study Links ADHD Stimulants To Risk Of Sudden Death
4. JAMA Study Slaughters Antipsychotics For Kids, Teens Paradigm
5. FDA Links ADHD Stimulants To Sudden Death In Healthy Children