Friday, November 30, 2012

ADHD: Stimulants, Alternative Treatments, and Criminality

Attention Deficit Disorders more than most I feel are diseases of civilization, particularly our hypermodern civilization. Certainly they are inherited, and many folks will show up at my office after a child has been diagnosed with ADHD, telling me, "you know what, I've always had trouble focusing as well." I've even seen old grade school report cards from the seventies, with neat teacher's script: "doesn't pay attention" "moves around too much" "too talkative" and "doesn't live up to potential." Of course there is controversy over the diagnosis, which is clinical, like every psychiatric diagnosis, and I have no doubt that a variety of different genetic and environmental influences on the frontal lobes are all swept together into a wastebasket diagnosis for the purposes of billing…on the other hand, sometimes I think the most good I do with the medicines at my disposal as a practicing psychiatrist is the judicious use of stimulant.

Now more than ever, in our world of 25 different passwords and constant stimulation and distraction, anyone who has a bit of ADHD potential may find himself quite debilitated. As a child where the only job you can have is school, if school is a problem (and school seems increasingly driven by perfect conduct and test scores), life becomes difficult. With classic hyperactive ADHD, if the child isn't the personable class clown, he may find himself ostracized by classmates who don't appreciate his distraction and hyperactive behavior. Many adults will have gone from job to job, rarely successful, and will often have a long track record of broken relationships and disappointments. Back in hunter-gatherer times, ADHD tendencies may have been an advantage, and one aspect of ADHD is to be able to "hyperfocus" during a crisis or on activities in which one has an emotional interest.

5% of the children in the western world meet criteria for ADHD (though in the US, the most recent CDC statistics show an increase in diagnoses from 7% to 9%.)

A recent study (from the New England Journal of Medicine, meaning it is a hot ticket)  made big headlines: Medication for Attention Deficit Hyperactivity Disorder and Criminality (hat tip to Dallas and every major news outlet). This study is one of those "wow socialized medicine with the very large registries makes for interesting data-gathering" sort of studies.

So, the researchers gathered data from 25,656 patients diagnosed with ADHD in Sweden between 2006 and 2009. They checked out the pharmacologic treatment and criminal convictions to compare the rates of convictions while receiving medicine or not receiving medicine. In short, criminal convictions decreased 32% in men and 41% in women if they were taking medication for ADHD compared to times while not taking medication. ADHD has previously been associated with criminality (1)(2), so it makes sense to investigate the circumstances more closely.

But the primary pharmacologic treatment of ADHD is controversial: stimulants. Ritalin and adderall in many, many different formulations. Stimulants are, in fact, much less potent versions of methamphetamines. They act on dopamine receptors (though, as always, it's complicated). What happens to a child's brain and body on stimulants over years and years? What happens if he or she has untreated ADHD and is not on stimulants? Those questions are important, but we don't really have the answers. Of course behavioral modification and accommodation at school also are big parts of appropriate therapy for ADHD.

Numerous studies have shown the short-term efficacy of stimulants in folks diagnosed with ADHD. Long-term it starts to get more murky, and most people discontinue medicines at one point or another (while many grow out of the "hyperactive" part, the inattentive piece often persists for a lifetime). By 36 months of treatment, many of the positive effects seen at 14 months are diminished (3). Questions have been raised as to the risks of stimulants with respect to tolerance, dependence, growth retardation, insomnia, psychosis, abdominal pain, decreased appetite, overprescription, and addiction (though a meta-analysis of studies of stimulants started in childhood show decreased risk of substance abuse later on compared to individuals with ADHD not treated with stimulants). 

In the large Swedish criminality study, the ADHD cases (16,087 men and 9569 women) were each matched with 10 controls according to year of birth, sex, and geographic location at time of diagnosis. Those who were defined as "in treatment" with stimulant medication included those who received at least 2 prescriptions within a 6 month period. 6 month intervals without prescriptions was defined as not receiving medication treatment. The outcome measure was any convicted crime (convictions in Sweden are supposedly independent of mental health diagnoses though a diagnoses may influence sentences). Date of the crime was used for the most part, but if none were recorded, the date of conviction was used. Confounding diagnoses (oppositional defiant disorder, antisocial personality, and substance use disorders) were also accounted for as well as whether or not a conviction would have interrupted medication treatment. In order to address the very obvious confounder that patients who decide to take medications are also perhaps at a point where they are making major changes with their lives, they also adjusted for non-medication treatments and the use of SSRI medication. Criminality was still highly associated with periods of time while not on stimulant medication. There was no long term association between use of stimulants for ADHD in 2006 and criminality in 2009. 

All in all, this is an observational study with the typical limitations, but the results are consistent with previous smaller studies. While there are many influences on ADHD behavior including diet in children, all treatment modalities are worth consideration.

That said, there is an interesting new article in Psychiatric Times by Dr. James Lake reviewing the alternative medicine treatments for ADHD. Up to 50% of families with a child diagnosed with ADHD will try an alternative therapy (typically diet or some sort of vitamin supplement), but supposedly only 10% admit the use of these complimentary treatments to the pediatrician.  

Studies of omega 3 fatty acids have been mixed. The most promising one used high doses (>16 g) of EPA and DHA. French maritime pine bark (Pinus pinaster) extract was effective in a couple of very small studies. Brahmi 50mg twice a day also fared better than placebo in a randomized controlled trial of 36 children. Zinc (up to 150mg daily) has helped in a few trials, and also as an augmentation strategy for stimulants. Iron was also shown to be helpful in children with low ferritin (but who weren't iron deficient by other measures). Carnitine has had mixed results. None of these herbal treatments have nearly as much evidence as the stimulant treatments, and the long term effects for all treatments are unknown. 

"Green play" is also a studied remedy for ADHD. Children who spend more time out of doors playing tend to have fewer symptoms of hyperactivity and inattentiveness (4). This study has some serious limitations, though it is difficult to imagine how more playing outdoors wouldn't be helpful for hyperactive children in particular. 

All told, in this modern world, ADHD can be a huge impairment, though it does have some advantages. I'm all in favor of green play and behavior and dietary modification first, but sometimes further medical interventions are necessary. 

Next up will be OCD!


16 comments:

  1. The great irony is, in Sweden, taking stimulants is otherwise harshly punishable by law. [1]

    "Criminal convictions in Sweden" is a very weak metric of actual criminal activity.

    [1] http://www.parl.gc.ca/Content/SEN/Committee/371/ille/library/gerald-e.htm

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  2. I am currently reading a fascinating book on Executive Function by ADHD expert Russell Barkley. His is trained as a neuropsychologist and debunks the idea that neuropsychological tests are the goal standard for assessing frontal lobe function. He prefers checkslists of social behaviors and cognitive problems. He makes a very sound case for it. He also talks about the neurodevelopmental basis for the disorder and there is an accumulating data base on that side of the story. Barkley uses an extended phenotype model of executive function and concludes that the commonest deficiencies seen in ADHD can be best accounted for using that model.

    At a recent seminar that I attended - his review of omega-3/6 FFAs were "mixed". Effect sizes were small to moderate (0.25-0.56)and a Cochrane meta-analysis apparently concluded no effects noted on parent or teacher ratings. Additional refs below:

    http://www.ncbi.nlm.nih.gov/sites/myncbi/collections/public/1bKYFbuqr01nbYE_XTH1oU/

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    1. Lake reviewed the Barkley study in the article I linked. You are reminding me of a neuropsychiatrist who gave us a lecture in residency. He was a dementia specialist, and told us to always focus on the executive function. Simple checklist measures of executive function in mild disease for the most part was a far better metric of disability than neuropsych testing of apraxia or even menory problems. I think the same would be true of ADHD. In my clinic, I look for a lifelong consistency of the problem and family history as clues… typically my patients are presenting with anxiety or depression symptoms which are often secondary to the ADHD, so it can be a little tricky. Thanks for the link!

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    2. I would like to see an ADHD cohort having 3D CT airway studies done. What percentage of individuals diagnosed with ADHD have severe restrictions in airway due to poor development of facial structures or enlargement of tonsils/adenoids or all of the above.

      My adult patients with ADHD have severe sleep apnea with O2 sats down in the low 80s. The ones with ADD have high hypopnea scores with O2 sat scores down to 86% but usually in the low 90s.

      The brain needs oxygen. The prefrontal cortex is the most sensitive part of the brain to low oxygen sats.

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  3. Very nice summary of a complicated issue. It would be interesting to go back 50 years to see what label psychiatrists and teachers were giving to ADHD kids. If it's really one in 10 US children, maybe it's not a "disease," but a subset of normal human behavior that doesn't fit in with the modern world very well.

    -Steve

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    1. My kindergardener gets 2 recesses a day, and 3 on the day she has to stay late while I am teaching. In all honesty, if she got maybe 90 minutes of "class" and the rest was running around, napping, or free play/coloring/crafting, I would be very pleased with her education.

      The ADHD advantage is very interesting, with respect to hyperfocus. Doctors with ADHD will tend to gravitate toward surgery, for example. I can see how this highly inherited "condition" has been maintained in the population at a fairly high level (5-10%). Our world is so distracting and overwhelming in some ways.

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    2. i guy i went to school with is a famous neurosurgeon. his dad told me he is the poster boy for ADHD. but he always did well in school- so that seems contradictory.

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  4. I started having ADD (the not-focusing part, not the hyper-activity one) at the age of 12. That was the time that my family moved from our mountain village in Greece to a small town nearby. In the village, we had our own chickens and eggs (have you ever had 3-4-year old hen? so delicious compared to the 3-6-month old chickens we can buy these days), and our extended family would give us goat meat whenever they would kill one in their herd. But most importantly, we had our own garden, with our own vegetables. And we would have our own bread, lacto-fermented for many hours before we baked it in our fireplace.

    And then, we moved to the small nearby town. Nutritionally, everything changed. We lost our garden, our chickens and organic eggs, and our fermented bread. We were buying everything ready-made, from the grocery store, and we started eating more pasta, since we were very poor.

    That's when my troubles started: I could not focus anymore as well as I could in primary school. I was a stellar student before, and I continued being a good student in middle school, but every year was becoming harder for me. Things turned really bad when I got to high-school. My grades fell to the floor, and no one understood why (especially my older teachers, who had seen a lot of potential in me). I just couldn't focus to study.

    Scratch that.

    I just couldn't read, period. Given that I was the intellectual in the family, this just didn't make any sense. I would try to read, and after 5 seconds my mind would wander away! I just couldn't keep it in place. I made it through high-school only because I was smart and had high critical thought, not because I studied.

    At the age of 16, my hair started falling out too. And things went completely to hell when I moved to the US 13 years later, since the wheat here is different than in Europe, more difficult to digest. I spent 10 years here in the US being extremely sick with various ailments, and I didn't know what was wrong. Every time I would go to Europe to see my family, my symptoms would subside a little, but I couldn't figure out that it was primarily the wheat to blame.

    In September 2011, I found Paleo. And it has changed my life. Not only almost all of my health problems have lifted, but so has ADD. I'm right now 39 years old, and in the last year I've read 5 books. While this might not be too many books for some book lovers out there, consider that my last out-of-school book-reading happened was when I was 13 years old!

    As far as I'm concerned, I don't have ADD anymore. I do Paleo and occasionally Paleo-ketogenic (up to 50gr net carbs on average), plus home-made goat kefir (fermented for 24 hours to remove most lactose, and goat/sheep/buffalo casein is gentler than that of modern cows', so there are no problems with it Paleo-wise). I found goat kefir to be a savior for me.

    Sometimes I get really sad though about all the missed opportunities in my life, just because I couldn't study anymore. In Greece you had to pass exams to get to the university (there were no private colleges at the time), so if you didn't make it in, you would be a low worker for the rest of your life. I eventually made it to the FIRST round of private colleges that appeared in Greece in the early '90s. I still couldn't study hard for it, but I made it through because I had real passion for computers, so I could figure things out myself, rather than through studying.

    To make the long story short: my life would have been completely different if my family didn't move to a "civilized" town when I was a kid. My ADD started when we moved there and our diet shifted from village-diet to modern diet.

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  5. Speaking first hand from experience to-date for our son (diagnosed at age 5 ADHD; age ten diagnosed with mild Asperger's), I can definitely say that stimulants have been key to his treatment plan. I also firmly believe (again based upon first hand knowledge) that these individuals (and their caregivers) need to seek a multifaceted treatment approach. Stimulants definitely helped our son successfully navigate elementary and now middle-school. But we keep an extensive support team and work very hard at teaching our son (and the school district) how to use his skills and strengths.

    Those affected with ADHD will need to live their own lives in an independent manner at some point. Given the deficits ADHD individuals experience in executive functioning, organizational skills, possible social skills weakness, etc... - this can be daunting. However, these skills can be practiced. We have found that in conjunction with stimulants, the effectiveness related to generalization of these skills increases. What is fascinating is his own desire to continue pursuing knowledge for these skills. He gets the fact that his brain works differently but knows that there are avenues for him to learn how he can overcome the bumps in the day-to-day life that seem more frequent for ADHD individuals.


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  6. Do you know Bruce Wexler from Yale School of Medicine? He's getting some pretty exciting results using computer games combined with physical exercises. Kinda neat stuff.

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  7. I think that ADHD is largely a disease of undetected iron deficiency.

    My own experience with iron has caused me to completely reevaluate how iron status is evaluated. I am no longer convinced that ferritin is a reliable indicator, and I think the risk of iron overload is overstated. There's some evidence that ferritin levels increase naturally with age, and this may not have anything to do with inflammation at all: http://ajcn.nutrition.org/content/78/6/1225

    (And honestly -- where is the evidence from basic research that ferritin can be correlated with iron status as measured by bone marrow staining? I haven't been able to find it. Bone marrow aspiration is a nasty business; good luck trying to find healthy patients for a study!)

    I have family members who are schoolteachers and have ADHD kids in their classes; so far, they've managed to convince a few of the parents to get their children's iron levels checked, and every one has come back deficient, even by the arguably soft criteria we currently use. As this is not a routine test in children, I suspect that many more of the kids are low in iron. This shouldn't be surprising when you consider the amount of dairy the average child is hammering back: fruit yogurt and chocolate milk is the stable of the school lunchbox.

    Mary Pickett gave a great talk last year on the idea of functional iron deficiency in the brain: http://www.ohsu.edu/edcomm/flash/flash_player.php?params=2%60/hosp/ohsuclin/gr100510.flv%60vod&width=640&height=480&title=Restless%20Legs,%20Tics,%20%20and%20ADHD:%20Iron%20Deficiency%20to%20Blame

    It is against this background that the Canadian Infant Feeding Joint Working Group is revising its guidelines, specifically recommending that first complementary foods be iron-rich: "Infants should be offered iron containing foods two or more times each day. They should be served meat, fish, poultry, or meat alternatives daily. The amount of food offered should be guided by the infant's hunger and satiety cues (PAHO, 2003)." http://www.hc-sc.gc.ca/fn-an/nutrition/infant-nourisson/recom/index-eng.php#a7

    Pureed meat! Yum!

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    1. Maybe really it's not the iron but the zinc, for which there is no test.

      A study done in Africa (which was imo totally unethical) determined that zinc supplementation either directly or via beef jerky improved behaviour and school performance compared to children who received a placebo. Teachers were not informed as to which child received what. However, after it was determined that zinc is a positive, the researchers went home and the children returned to their previous zinc deficient state. That is unethical.

      Childrens' diets these days are quite pathetic.

      I'm beginning to consider recommending 4 slices of high fibre Wonder Bread per day. It may not be 'chichifoofoo' but for poor people living on the edge, a product like WonderBread will provide them with almost all vitamins and minerals

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    2. WonderBread will create other problems. You might be able to fix zinc (it's not for sure, since wheat blocks the absorption of nutrients that itself and other foods contain), but leaky gut will start happening, which creates worse things than ADHD.

      Besides, Wonderbread only has 10% of zinc per slice.

      If you want zinc, you go and buy (or fish) the right food: oysters and mussels. That's where zinc is at. If you have shellfish once or twice a week, that's all you need. A portion of oysters has 800% of zinc, not that measly 7-10% that Wonderbread has.

      This reminds me of all these people who say that for potassium, you just "eat a banana". Little do they know that bananas have only 10% RDA potassium. If you need to supplement hard with it, you either go for potassium salt (supplementation pills are useless for potassium), OR, you eat beetroot *greens* that have 60% of the RDA in their leaves. But no one talks about beetroot greens somehow...

      Anyways, of course, if you're living in the middle of Africa, you might not be able to find shellfish. In that case, you will have to supplement. A bottle of 333% RDA Zinc shouldn't cost more than a few Wonderbreads, and if there's some rudimentary health system, it could be prescribed for cheap.

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  8. Pardon any repetition of information in the above posts, but there are several important points you address which align with a conversation I had with my pdoc this week. (I'm an adult with Bipolar Disorder, very high-functioning but I still have my problems). We started discussing the changes in the DSM-V, in regards to diagnosing children with BPD and the focus on behavior. We were both in agreement that introducing drug-therapies in children before their brains have time to develop can be risky, and therefore behavior modification should be a first line of treatment (and I am biased because I have a background in behavior modification with children (and husbands)). As an adult, I consistently struggle with prescription tolerance, and it's not something I want to see in children. Just like BPD, I believe that when managed and harnessed in the right way, ADHD can often have many benefits.

    This may take us a little off topic, but my pdoc and I also discussed my husband's inability to focus on work tasks and his "nature" to put out every fire without any regard for his personal well-being. As a child and through young adulthood, my husband never had any problems that could be described as "ADHD" symptomatic. However, when he went through Army Ranger school and did two tours in Iraq (special ops), he came back a changed person...he was taught to always scan the environment, react quickly, and always keep moving. He was also trained to go long periods of time without sleep, and as an end result can easily work 24 hour shifts. There is not doubt in my mind that my husband responds to stress as a soldier would. We are looking at possible use of stimulants to channel this extremely limiting behavior(s) he acquired into something useful. My doctor treats sees this in other similar patients and would love to do more research but is limited by time and money. Everyone can relate with that!

    So to my point, I fully believe in the genetic component that leads to various mental health issues. I deal with it every day. However, I also believe that malleable young minds can be molded, and ultimately the brain chemistry can adapt to a more functional and adventitious level and hopefully limit the chances of criminal behavior.

    Check out the Boystown Social Skill Model, if you want to try behavior modification. Just reminder, like any other regimen, you have to be consistent.

    Thanks!

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  9. Hi Emily, I've been searching about ADHD on the past few days and found your blog as an interesting and very informative. I want to ask question about the product I bought from mercola at zinc deficiency where i am doubtful about? Is this product an effective one for my teenage child who have ADHD?

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  10. One thing to consider is that OCD can be mistaken for ADHD. I found this out the hard way since this isn't apparently well recognized in the medical community. My oldest child was diagnosed in elementary school with severe ADHD. She was diagnosed with a stimulant medication which did not help her. It was all the doctors seemed to know how to do; trade out one ineffective stimulant for the next.
    Someone who is severely OCD can appear to be ADHD. She was so locked up in her own world, she couldn't attend to the world around her and she did not care. She failed at school from kindergarten through high school because she did not care about the same things everyone else does. She was that absorbed into her own interests. The problem with stimulant meds was that they indeed made her focus more, but that was the last thing she needed: more intense focus. Stimulants just made her more agitated to be torn away from her circular thoughts. Finally, at age 17, I begged the psych. to try an SSRI. This was the first time improvement was seen in her ADHD symptoms. She was now able to "let go" enough of her world to attend to the tedious things in life that took her away from her compelling circular thoughts. She does exhibit other signs of ADHD that are classic, but the core of her ADHD are OCD-based. I'll admit, the SSRI was not a cure by any means and she still struggles greatly, but it was definitely a means of relief for the first time ever. I wish I could say she is out of the woods. She is 19 and struggling, unable to hold a job. I'm having a hard time helping her since she is an adult and her younger sibling is autistic and far more impaired. I just hope this aspect of the ADHD/OCD connections becomes more widely recognized by doctors for subsets like my child so no one has to go that long running down the wrong path.

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