Saturday, July 25, 2009

Scientific American goes nuclear on Ritalin

Edmund Higgins, a clinical associate professor [1], has written a blistering attack on Ritalin, and gotten it published in Scientific American – a magazine that’s presumably sharing the industry’s revenue problems.

Dr. Higgins compares Ritalin (methylphenidate) to methamphetamine. This is the rhetorical equivalent of comparing a human to Hitler; it’s chemically correct but it’s the mark of a crank. It’s a Godwin’s Law violation.

On the other hand, as someone who’s child has been on Ritalin and other ADHD meds for years, I’ve long had the same sort of concerns. Ritalin has an astounding safety record, but we’re messing with the neurochemistry of a rapidly evolving brain over a period of years and decades. I personally wouldn’t use this, or any other, long-term psychiatric medication medication in my child unless all other options had been exhausted and the disability and risks of non-treatment were severe. I’ve previously made the comparison to treating cancer. Nobody should expose a child to life threatening chemicals with severe long term effects– unless the alternative is worse.

Another point in Higgins favor is his interest in animal models. Given the immense difficulty of studying psychiatric medications in children, animal models are pretty much all we’ve got. So let’s see what he says about the animal models, stripping out some inflammatory rhetoric and considering only studies of meds used to treat ADHD. Note that much of this research is more recent that a 2006 review of mine that was pretty reassuring, but that means it won’t have been validated by other researchers …

Do ADHD Drugs Take a Toll on the Brain?: Scientific American

Edmund S. Higgins is clinical associate professor of family medicine and psychiatry at the Medical University of South Carolina and co-author, with Mark S. George, of The Neuroscience of Clinical Psychiatry (Lippincott Williams & Wilkins, 2007) and Brain Stimulation Therapies for Clinicians (American Psychiatric Publishing, 2009).

… In an experiment published in 2003 psychiatrist Eric Nestler of the University of Texas Southwestern Medical Center and his colleagues injected juvenile rats twice a day with a low dose of methylphenidate similar to that prescribed for children with ADHD. When the rats became adults, the scientists observed the rodents’ responses to various emotional stimuli. The rodents that had received methylphenidate were significantly less responsive to natural rewards such as sugar, sex, and fun, novel environments than were untreated rats, suggesting that the drug-exposed animals find such stimuli less pleasurable. In addition, the stimulants apparently made the rats more sensitive to stressful situations such as being forced to swim inside a large tube. Similarly, in the same year psychiatrist William Carlezon of Harvard Medical School and his colleagues reported that methylphenidate-treated preadolescent rats displayed a muted response to a cocaine reward as adults as well as unusual apathy in a forced-swim test, a sign of depression.

In 2008 psychopharmacologist Leandro F. Vendruscolo and his co-workers at Federal University of Santa Catarina in Brazil echoed these results using spontaneously hypertensive rats, which—like children with ADHD—sometimes show attention deficits, hyperactivity and motor impulsiveness. The researchers injected these young rats with methylphenidate for 16 days at doses approximating those used to treat ADHD in young people. Four weeks later, when the rats were young adults, those that had been exposed to methylphenidate were unusually anxious: they avoided traversing the central area of an open, novel space more so than did rats not exposed to methylphenidate. Adverse effects of this stimulant, the authors speculate, could contribute to the high rates of anxiety disorders among ADHD patients…

… In February 2009 neuroscientists Yong Kim and Paul Greengard … injected … mice with either methylphenidate or cocaine daily for two weeks. Both treatments increased the density of tiny extensions called spines at the ends of neurons bearing dopamine receptors in the rodent nucleus accumbens. Compared with cocaine, methylphenidate had a somewhat more localized influence; it also had more power over longer spines and less effect on shorter ones…

Furthermore, the scientists found that methylphenidate boosted the amount of a protein called ΔFosB, which turns genes on and off, even more than cocaine did…

So when I strip out everything else, the bulk of Higgins’ article is coming from 3 animal studies in 2003, 2008, and 2009. All of the studies involved injecting methylphenidate, which is not how it’s used in humans. Injecting Ritalin is a mark of abuse with pretty different pharmacology from oral use.

The most interesting of these articles is Nestler et al in 2003 [2], an article with a rather strange title (emphases mine – incidentally, Nesler is the last listed author, so why did Higgins credit the study to him?) …

Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood.

Bolaños CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ.
Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
Biol Psychiatry. 2003 Dec 15;54(12):1317-29.

BACKGROUND: Methylphenidate (MPH) is a psychomotor stimulant medication widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Given the extent of prescribed use of MPH, and because MPH interacts with the same brain pathways activated by drugs of abuse, most research has focused on assessing MPH's potential to alter an individual's risk for adult drug addiction. Data examining other potential long-term behavioral consequences of early MPH administration are lacking, however. METHODS: We investigated the long-term behavioral consequences of chronic administration of MPH (2.0 mg/kg) during pre- and periadolescent development in adult rats by assessing their behavioral reactivity to a variety of emotional stimuli.
RESULTS: The MPH-treated animals were significantly less responsive to natural rewards such as sucrose, novelty-induced activity, and sex compared with vehicle-treated control animals. In contrast, MPH-treated animals were significantly more sensitive to stressful situations, showed increased anxiety-like behaviors, and had enhanced plasma levels of corticosterone.
CONCLUSIONS: Chronic exposure to MPH during development leads to decreased sensitivity to rewarding stimuli and results in enhanced responsivity to aversive situations. These results highlight the need for further research to improve understanding of the effects of stimulants on the developing nervous system and the potential enduring effects resulting from early-life drug exposure.

Why did I say that was a “strange title”? Because an article on rats in a journal called Biol Pyschiatry would normally contain the word rats in the title.

If we simply scaled the dose to humans, but the way, this would be 80 mg (twice daily?!) by injection – which would be a whopping abuse dose in humans. The article has gotten very little attention in the past six years, being cited only four times of which two appear to be reviews.

A related articles query produced a very large number of similar rat studies, including one that, surprisingly, found no effects (surprisingly, because these look like “fishing expedition” studies, when you include publication bias they almost always show some effect.) These are boom times for rat studies of methylphenidate, probably reflecting new NIH funding.

On review I’m left with several only mildly related conclusions …

  1. I’m happy the animal studies are being done. I’d like to see fewer fishing expeditions, and more replication of results. For example, repeat the Bolanos study with a larger group, maybe a different clonal line, and see if the same results appear. These need to be registered studies, so we don’t get messed up by publication bias (which is a huge problem in the low cost animal studies domain). I would really like to see more studies of tolerance effects in rats.
  2. Higgins may turn out to be correct (lots of people are suspicious that stimulants can be used so long, including me) but I think he’s got a crank agenda. His article is more inflammatory than the evidence supports. A more sober article would have been welcome.
  3. You shouldn’t put children on psychoactive medications without a very good reason. Of course that was always true.
  4. Don’t assume any other medications are in any way safer – Ritalin has been studied far more than, say, Stratera.
  5. Scientific American is running out of money. We’ll know they’ve hit rock bottom when they do an article on the scientific evidence for Creationism. They should have known better than to publish this article in its current form.

[1] I have a similar sort of title today, and have had similar roles in the past. In the hierarchy of academia, this title carries less glory than research assistant.

[2] Parenthetically, why does PubMed make it so very hard to find the link to a citation? It’s like they’re trying to hide things.

Monday, July 13, 2009

Autism Society of America: Summer Tips

Last summer we passed on our experience with years of autism on the road. It was tough when the kids were younger, but our last few trips have been fairly agreeable. They even did pretty well when my back put me flat on the van floor for a few days.

We're going for another two week road trip this August, and everyone's looking forward to it.

So we can vouch for some of these Autism Society of America Summer Travel Tips (my comments in square brackets)
  • Plan in advance. Call ahead and inform the airline, hotel, resort and cruise line of the individual’s situation and inquire what special accommodations - fridge, inside room - are available. [We stick with road trips or relatively solitary low stimulation cabins. I don't think we'd try a cruise. Fridge inside the room - definitely. Calling ahead? Never have. It would just make most places too anxious.]

  • Bring the individual’s bedding if you think that will make him more comfortable. [We bring "blankies" and other comfort objects.]

  • Be realistic in selecting vacation destinations with environments you believe the individual can handle. [We like to get experience first in more limited environments. We've gradually extended our airplane distance.]

  • Book low season on a cruise or at a resort so there will be fewer guests and the staff will have more time to devote to your needs.

  • Travel by car if flying or other public transportation seems too difficult. [Definitely.]

  • Choose hotels/motels with kitchen suites or room service so you can eat some of your meals in your room. [Definitely]

  • MP3 players with headphones, loaded with favorite music, can soothe individuals who are disturbed by noises. Personal DVD players can also help make a long trip more enjoyable. [Absolutely, but we stagger them. It's easy to overdose. Music for a while, then books on tape/CD, then one movie a day.]

  • Don’t hesitate to explain the individual’s situation to others you may encounter, including flight attendants, hotel staff, employees at the amusements you visit, and other vacationers. ["Autism" is a good cover story for a lot of things.]

  • Prepare the individual before and during the trip on what to expect that day. [One of our kids needs a pretty detailed schedule, but he's surprisingly good about deviations. He just has to know the plan.]

  • Adhere as closely as you can to the individual’s normal routine. [Huh? The normal routine doesn't involve travel. Maybe they mean bedtime rituals?]

  • Whatever happens, stay calm. [When one parent gets stressed too much, they take a walk. It would be tough to do it solo.]

Sunday, July 05, 2009

The perils of judgment

Take one:
Two children, one dog, one weather beaten father. July day, maybe a bit hot. Lovely though.

One child shouts too much. The other seems old to be so cranky and tearful. Dad seems a bit passive. Really, he should put his foot down.

Parental grade: C-, and that's only because fathers get off easy.
Take two:
Two children with autism and a few more challenges besides. A day of bicycling (yes, and that was a great victory x 2) with Dad to a secret trail, rappelling down a bluff face to the river, playing with the dogs, tossing balls, drawing in the sand, exploring the river, drying sandy feet and managing wet underwear.

Constant negotiation, pushing the envelope of abilities and anxieties. The dog's pretty easy, but she gets upset if she can't see and touch all of her pack - especially when she's in her bike trailer.

Parental grade: Off the charts that neurotypical parents use.
Me, I don't judge nobody.

Thursday, July 02, 2009

Tar Heel Reader - online picture book library

Years ago I thought about starting a web site for friends and families to create short picture books for children with reading difficulties.

I never got very far, but, happily, the University of North Carolina went all the way (their reading center also sponsors the summer literacy program at Camp Courage Minnesota our son recently completed). I've read a few of these online picture books and they're really quite good.
Tar Heel Reader

... Welcome to the Tar Heel Reader, a collection of free, easy-to-read, and accessible books on a wide range of topics. Each book can be speech enabled and accessed using multiple interfaces (i.e. switches, alternative keyboards, touch screens, and dedicated AAC devices). The books may be downloaded as slide shows in PowerPoint, Impress, or Flash format.

You may write your own books using pictures from the huge collection at Flickr or pictures you upload....

... We have books that are intended for teenagers who are just learning to read. You may find some books that are inappropriate for your students; don’t use those. We recommend you learn about the Favorites page as a way to present your students with reading choices that you approve...

.... This site is a result of a collaboration between Center for Literacy and Disability Studies and the department of Computer Science at the University of North Carolina at Chapel Hill.
We'll see how well they work with our struggling reader.

I've asked them if they'll look into a version of the site optimized for an iPhone/iTouch.

Update: they have a blog, but as of 7/3/09 the feed doesn't work quite the way one would expect. Try this URL instead: It worked for me.